|Year : 2011 | Volume
| Issue : 2 | Page : 178-189
Abstracts of Oral Presentations
|Date of Web Publication||12-Nov-2011|
|How to cite this article:|
. Abstracts of Oral Presentations. World J Nucl Med 2011;10:178-89
A custom-built Software Tool for Data Storage and Analysis of Acquisition and Processing Parameters for Tc-99m and Tl-201 MPI with Different Imaging Systems
C. Yiannakkaras, I. Chrysanthou-Baustert, O. Demetriadou, Y. Parpottas, S. Christofides, C. Costantinou, D. Kaolis
Nuclear Medicine, Nicosia General Hospital, Nicosia, Cyprus
Introduction: Nuclear cardiology imaging using SPECT systems is currently used as a common daily routine diagnostic tool. Converting raw data into diagnostic images as well as other diagnostic parameters constitutes a complicated process that involves numerous acquisition, reconstruction and processing parameters. Hence, the effect of each individual parameter, and further, the clinical relevance of different combinations of parameters need to be investigated in order to determine the most appropriate combination for a particular setting (i.e. acquisition, reconstruction and processing hardware and software). This work aims at developing a software tool that is able to store and analyze data acquired using a cardiac phantom and able to simulate different myocardial perfusion pathologies. This data represents cardiac SPECT and GATED SPECT imaging techniques recording acquisition, reconstruction and processing parameters involved in every step of the process.
Materials and Methods: All recorded data are hosted in a database written on SQL Server 2008 R2. During the first step, data entry forms have been designed in. NET framework using Visual Basic and Visual C#. The data entry forms have been designed so as to meet particular requirements. Apart from following the image acquisition, reconstruction, processing and reporting order so that the user is able to record the data in an ergonomic and failsafe manner, we have determined and used common entries for different imaging systems and commercial cardiac post processing packages. Additionally, we have included entries for a typical physician report. To achieve this, we have used imaging system manuals as well as EANM/ESC and ASNC imaging guidelines. The data presentation and analysis interface is designed using Visual Basic Applications (VBA) in Excel. Through the VBAs, data filtering and analysis tools have been constructed according to physicians' preferences to automatically present the data in a comprehensive flexible and ergonomic manner to the researcher.
Results: We have managed to design a software tool able to store and analyze data from different SPECT imaging systems in a consistent and structured manner. The system is further designed to accommodate differences or imaging protocols across systems, staff members or departments. A data retrieval presentation analysis module connected to our database is designed to offer the flexibility and speed to access and analyze data and produce results for this research. Furthermore, as data will be continuously added to the database the results will be continuously refined as a larger number of patients or phantom studies are added.
Conclusions: We have designed a database combined with a custom data manipulation interface that has the potential to become a valuable tool for researching best procedures in MPI, for training new staff in all aspects of MPI, for comparison between imaging systems as well as for further clinical research relative to MPI and coronary angiography.
Future Work: Apart from storing and analyzing cardiac phantom acquisition reconstruction and processing data our custom software tool will be expanded to accommodate patient data that will enable combined evaluation of MPI and angiography results.
115-Construction of a Dynamic Cardiac Phantom to Optimize the Diagnostic Value in SPECT Myocardial Perfusion Imaging
Y. Parpottas, I. Chrysanthou, O. Demetriadou, S. Christofides, M. Wasilewska-Radwanska, C. Yiannakkaras, D. Kaolis, T. Fiutowski, F. Sikora
Department of General (Physics-Math), Frederick University, Nicosia, Cyprus
Coronary artery disease (CAD) is the most common form of heart disease worldwide. Treatment of CAD depends on its severity. Myocardial perfusion imaging (MPI) has been proven to be able to assess the functional significance of coronary artery stenosis. While analytic models and patient data are useful, a reproducible, compartmented, mechanical phantom is critical to optimize MPI studies, patient dose, and calibrate imaging systems.
For this purpose, an electrocardiography (ECG) gated dynamic cardiac phantom with variable heart beats and ejection fraction as well as with capability of inserting various combination of defects, inserted in the RSD fully tissue-equivalent anthropomorphic phantom (male, oversize man, female), is constructed. The elaborated phantom models the different cases of cardiac failure and coronary artery disease. It is based on a twin membrane where the inner membrane acts as a barrier for the left ventricle and the outer membrane as a barrier for the myocardium. One or multiple permanent defects (multiple phantoms) are placed at specific locations within the myocardial wall to represent single, double or 3 vessel disease of different extend and severity (ischemia or infarct), and different volumes of the cavity represent different degree of left ventricular failure. The phantom is utilized to acquire ECG MP images with two SPECT (single photon emission computed tomography) modalities with different attenuation correction (AC) methodologies (low dose CT, Gadolinium lines sources) and of different analysis algorithms (OSEM, FBP), using the 201Tl and 99mTc-Myoview radiopharmaceuticals. Direct thermo-luminescent dosimetry (TLD) measurements are also conducted to determine doses to organs due to AC and/or radiopharmaceuticals. The protocol of acquired images with the best diagnostic value, considering dose constraints, will improve the nuclear physician΄s confidence. This work is funded by the Cyprus Research Promotion Foundation and the European Regional Development Fund through the project ΥΓΕΙΑ/ΔΥΓΕΙΑ/0308/11: Optimizing Diagnostic Value in SPECT Myocardial Perfusion Imaging.
Effect of Short Term Metformin Therapy Associated with Levothyroxine Dose Decrement on TSH and Thyroid Hormone Levels in Patients with Thyroid Cancer
S. R. Zakavi, L. Dourandish, Z. Mousavi, H. Rokni, R. Sadeghi
Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Aim: Suppressive therapy with levothyroxine is the main step in treatment of Differentiated thyroid cancer (DTC). However subclinical hyperthyroidism is associated with deleterious effect on cardiovascular and skeletal systems. Some case reports showed that Metformin might have a suppressive effect on TSH level.
Materials and Methods: We performed a single blind randomized controlled trial on effect of short term Metformin therapy on 56 non-diabetic patients with DTC under suppressive therapy with levothyroxine. Six patients excluded from the study and 50 patients (45 female, 5 male) with mean age of 39.68±8.7 years and completed follow up. Metformin (500mg) or placebo added to the drug regimen of the patients and levothyroxine dose decreased by 33%. TSH and thyroid hormone values were measured at the beginning of the study and 3 months after treatment.
Results: 46 patients had papillary and 4 had follicular carcinoma, 46 patients (90.2%) were in stage 1 and 4 patients (9.8%) in stage 2 of TNM classification. The mean dose of levothyroxine was 2.2±0.48 mcg/kg. The mean TSH level at the beginning of the study was 0.05 ±0.04 IU/ml. The mean age, weight and baseline TSH level was not significantly different between Metformin and Placebo groups (P>0.2). In Metformin group, the mean (±SD) TSH level was significantly increased from 0.03±0.04 to 3.1±5.7 IU/ml after 3 months of intervention (P=0.01) and the mean thyroid hormone levels were significantly decreased (P<0.001). In Placebo group, the mean TSH level was increased from 0.04±0.04 to 3.1±4.7 IU/ml after 3 months (P=0.003). Delta TSH was defined as the difference between TSH level before and after intervention and it was 3.0±5.6 IU/ml and 3.1±4.7 IU/ml in Metformin and Placebo groups respectively (P=0.9).
Conclusion: Adding 500 mg of Metformin to drug regimen was not able to compensate for 33% of levothyroxine dose decrement and keep TSH in the suppressed level in patients with DTC.
Breast Cancer and Autoimmune Thyroiditis: Does the Sodium Iodide Symporter Play a Role?
J. Pagsisihan, H. Nam, J. Eo, J. K. Chung, D. S. Lee
Seoul National University Hospital, Seoul, Korea
Breast cancer is the most common malignancy in women. Thyroid disease is likewise prevalent in the female population. On whole body PET/CT, increased thyroid gland uptake of F-18 Fluorodeoxyglucose (FDG) is sometimes encountered. It may appear diffusely or focally increased. Sodium iodide symporter is found in both the thyroid gland and breast.
Objective: This study aims to determine the incidence and evaluate the clinical significance of diffusely increased thyroidal uptake of F-18 FDG in breast cancer patients. This also aims to determine the possible role of NIS in thyroid disease among breast cancer patients
Methodology: The study population was comprised of 440 adult female cancer patients. Those who were diagnosed with thyroid and ovarian malignancy, as well as those with previous thyroid surgery, were excluded. Whole body PET/CT images and medical records were reviewed. The presence of NIS mRNA in the serum was determined using nested RT-PCR.
Results: One hundred thirty-three (30.2%) patients had breast cancer while 307 (69.8%) had malignancies other than breast cancer. Diffusely increased thyroidal uptake was demonstrated in 18.8% and 10.4% patients in the breast cancer group and non-breast cancer group, respectively. There was significant difference between these incidence rates. Diffusely increased thyroid uptake was more frequently noted in women 50 years old and above. The average SUVmax of the thyroid gland in breast cancer patients with diffusely increased thyroid uptake (3.33) was significantly higher than in those who did not exhibit increased thyroid uptake (1.25) (P<0.0001). In the patients with diffusely increased thyroid uptake, the average SUVmax of the thyroid gland of the non-breast cancer group (4.80) was significantly higher than that of breast cancer group (3.33) (P=0.021). There was no statistical significance in the incidence of diffusely increased thyroid uptake with regards to cancer stage and hormone receptor status. On further thyroid gland evaluation, autoimmune thyroditis was noted in the breast cancer patients with diffusely increased uptake. NIS mRNA was detected in serum of the breast cancer patients and was negative in all the normal controls.
Conclusions: Diffusely increased thyroidal F-18 FDG uptake was more frequently exhibited in patients with breast cancer. Further thyroid gland evaluation revealed autoimmune thyroiditis. NIS mRNA was detected in serum of the breast cancer patients. These are suggestive of an association between breast cancer and autoimmune thyroiditis and the possible role of NIS in the causation of this milder form of autoimmune thyroiditis.
The Assessment of Oxidative Stress and Hematological Changes in Patients with Differentiated Thyroid Carcinoma Treated with Radioiodine
M. Matovic, V. Jakovljevic, V. Tisma, M. Vlajkovic, M. Jeremic, D. Djordjevic, N. Barudzic, M. Vuletic, V. Zivkovic
Nuclear Medicine, Clinical Center Kragujevac and Medical Faculty University, Kragujevac, Serbia
The aim of our study was to assess the extent to which radioiodine therapy affects the onset of oxidative stress and the response of the antioxidant system to it, in patients with differentiated thyroid carcinoma treated with radioactive iodine. Furthermore, we also set out to determine hematological changes in these patients. Our study enrolled 45 patients of both genders (33 females and 12 males, average age 42.5±14.3 years, ranging from 19 to 65 years) after total thyroidectomy for papillary (39 patients) or follicular (6 patients) thyroid carcinoma. An increase in TSH blood levels was registered in all patients prior to 131I therapy (TSH>30 mIU/L). Radioiodine with an activity of 5.55 GBq was administered to all patients orally as sodium iodide. The levels of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H 2 O 2 ) and superoxide anion (O2-) as indicators of oxidative stress were estimated in plasma samples. The activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) was estimated in hemolysate of erythrocytes. All of the parameters were measured in appropriate samples prior to 131I administration (day '0') and on days 3, 7 and 30 following 131I therapy. Hemoglobin levels and the number of red blood cells, white blood cells and platelets were estimated for every patient from their blood samples in the above-mentioned intervals. The values of all of the parameters were expressed in relation to the initial value, as its percentages. We found a significant (P<0.05) increase in TBARS and O 2 - levels 3, 7 and 30 days following the radioiodine treatment (TBARS 165.7%, 146.4% and 157.3%; O 2 - 136.3%; 123.6% and 191.4% of initial values, respectively). We did not find any significant (P>0.05) changes in H 2 O 2 levels (109.3%, 94.9% and 96.7%) in these intervals. Following the therapy we found a significant (P<0.05) increase in GSH (105.2%, 194.4% and 118.9%), SOD (166.6%, 251.9% and 129.8%) and CAT (134.3%, 178.3% and 138.4%) levels as a result of oxidative stress. The peak of those levels was noted 7 days following the therapy. The number of all blood cells and hemoglobin levels were significantly (P<0.01) lower in all the measured intervals following radioiodine therapy (WBC: 84.3%, 84.8% and 79.1%; RBC: 96.4%, 97.6% and 93.1%; hemoglobin: 97.1%, 97.9% and 95.6%; PLT: 89.3%, 99.1% and 82.2%). We can conclude that radioiodine could facilitate or induce significant oxidant/antioxidant changes, as well as significant hematological changes in patients treated with this radionuclide.
Relationship between Radiation Absorbed Dose to the Blood and Successful Ablative Treatment in Thyroid Cancer patients
S. Fatima, J. Irfan, S. Farruk, T. H. Khan
Nuclear Medicine, Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad, Pakistan
I-31I therapy is used in the treatment of differentiated thyroid cancer to ablate the post-surgical thyroid remnant and to treat recurrent or metastatic cancer. The optimum administered activity for ablation remains controversial: the most commonly used method is the administration of a fixed radioiodine activity (1110-3700 MBq or more); an alternative is the administration of an activity individually calculated to deliver a prescribed absorbed dose (usually 300 Gy for remnant ablation and 80 Gy for treatment of metastasis). The cumulated activity per volume of blood was proposed to be a more adequate predictor for therapeutic success than the administered activity. The amount of 131-I available in the blood depends on the 131-I excretion rate, which varies considerably between individual patients. This results in large differences in effective half-life; and consequently in the residence time of the activity in blood. The determinant for a successful 131 I ablation is the radiation absorbed dose to the target tissue; the decisive parameters for this are the administered therapeutic activity and the retention of radioiodine in the target volume. Quantitative estimate of 131I dosage in metastases or thyroid remnants were performed in 20 Thyroid cancer patients. WB scans are taken at 3, 24, 48 and 72 hours post administration of scout dose of 131I. Dosimetry calculations were performed using MIRD techniques. Initial results of the study population showed strong positive correlation of blood absorbed dose with success of ablation.
Intra-articular Evaluation of Lu-177 Hydroxyapatite in Animal Model
M. Sohaib, I. A. Abbasi, M. M. Ishfaq
Department of Medical Sciences, Pakistan Institute of Engineering and Applied Sciences (PIEA), Nilore, Islamabad, Pakistan
Aim: Lutetium-177 (177Lu) is an adequate radionuclide for therapy. Due to favorable decay characteristics of 177Lu it is considered to be a promising radionuclide for the use in radiation synovectomy of small sized joints. Other advantages include its longer half life and large-scale cost-effective production. Hydroxyapatite particles are regarded as one of the suitable radiation carriers for synovectomy. The present work describes the bio-evaluation of 177Lu labeled hydroxyapatite particles in knees of animal models.
Materials and Methods: Both hydroxyapatite particles and 177Lu were prepared indigenously. HA particles were characterized by IR and X-ray diffractometry. Ca/P ratio was determined by ICP-OES. Animal assessment of the [177Lu]HA particles was carried out by injecting 5-10 MBq activity in 0.1 mL directly into knee joint space of two healthy rabbits followed by sequential image recording of their knees under Siemens Orbiter gamma-camera interfaced with ICON™ software fitted with low energy, high resolution collimator. Energy widow of 20% was set at 113 keV γ photons excluding 208 keV. Five minutes images were taken at 256×256 matrix size keeping nearly similar position of the animal. Eleven images over a period of one month were recorded for both the animals. The analysis of the images was performed visually for extra-articular activity, and quantitatively by drawing regions of interest (ROIs) over the activity in the joint and extracting the background subtracted counts. Counts were analyzed by semi-log plot and exponential line-fit which exhibited the disappearance of Lu-177 HA activity from the synovial cavity. It was compared with physical decay of Lu-177.
Results: No visible activity in any other organ was identified in all the images. Analyses of images acquired at 11 time-points i.e. at 0, 2, 3, 22, 45, 217, 241, 290, 386, 602 and 722 hours showed steady fall in the counts in the injected knees of both the rabbits. Exponential fit to the disappearance exhibited half-lives of 154 hours and 158 hours for rabbit 1 and 2 respectively. There was a minimal downward divergence of disappearance of knee activities from the theoretical decay of Lu-177 (T1/2 = 161.5 hours). This suggests insignificant loss of the activity from the joint space in general body fluids. The biological half life of the agent in the knees calculated from the above data was >190 days.
Conclusion: Study of 177Lu-labelled hydroxyapatite in animal models has shown virtually no leak of the agent from the knees joints.
Development of Colloidal Samarium Phosphate [32P] Injection for Radiation Synovectomy - A New Therapeutic Radiopharmaceutical Agent for the Treatment of Joint Disorders
P. Ganti, U. Sheri Kumar, Y. Teje, M. H. Bhatia, S. S. Sachdev, S. Nagalingam
Department of Atomic Energy, Board of Radiation and Isotope Technology, Navi Mumbai, India
Local instillation of radio-colloids of pure beta emitters such as 32P and 90Y and beta, gamma emitters such as 153Sm, 166Ho and 186/188Re have shown promising therapeutic effect; for example, radiosynoviorthesis (RS) and intra tumoral therapy (ITT). Colloidal Chromic [32P] phosphate dispersion has been used for pleural and peritoneal effusions, secondary to primary malignancy and 90Y-silicate/citrate colloid, 153Sm-hydroxy apatite, 186Re-sulphide colloid are used for the treatment of rheumatoid arthritis. Keeping in view the demands of Nuclear Medicine Physicians in India, for an indigenous substitute for imported and expensive colloidal 90Y-silicate injection, we have undertaken the development of 32P based radio colloid, 'Colloidal Samarium Phosphate [32P] injection, (SMPC)' for RS applications. The method of preparation is based on the reaction of carrier SmCl3 with phosphoric acid doped with [32P]-H 3 PO 4 , followed by the addition of gelatin (Haemaccel) solution to form a true colloidal dispersion. Near quantitative yields of SMPC were obtained in typical batches with radiochemical yields more than 90%. The pure product, recovered by dialysis, was formulated in isotonic saline solution. The product was dispensed aseptically and then sterilized by autoclaving. The radiochemical purity was found to be not less than 98% as assessed by paper chromatography. The product retained its radiochemical integrity throughout the stability study period of 14 days. Particle size was determined on equivalent cold formulations of SMPC, using laser diffraction particle size analyzer. 70% of the particles were in the range of 1-5 μM, which is ideally suitable for radiation synovectomy (RS). The product was evaluated for its biological efficacy with 0.1ml of 32P-samarium phosphate colloid (approximately 1 mCi) instilled into the rabbit knee joint. The joint was immobilized and images of the joint were acquired. Complete retention of the instilled product at the knee joint and absence of leakage into systemic circulation were observed for 96 hours. Eighteen batches of the colloidal Samarium [32P] Phosphate injection were prepared in BRIT radiopharmaceutical laboratory facility. All the batches complied with the physic-chemical tests, sterility test and bacterial endotoxin test. With the approval of Radiopharmaceuticals Committee (RPC), clinical trials were undertaken as per the guidelines in seven premier Nuclear Medicine Centers in India. Clinical studies on patients were carried out after preclinical testing and investigation for the confirmation of resistant synovitis. Clinical protocols for intra-articular administration were established and follow-up observations were also conducted. Around 250 trial consignments of 500 mCi were used in these studies. More than 150 knee joint studies were carried out. 1-3 mCi was injected per knee joint for adult subjects and 0.5-0.7 mCi dose for children. Cases under this clinical trial consisted of 54 cases of Hemophiliacs, 86 cases of Rheumatoid Arthritis and 17 cases of Osteoarthritis and others. The parameters observed for clinical follow-up during six to ten months follow-up period were, pain relief, swelling, range of movement (ROM) of the treated joint and frequency of bleeding in the case of hemophiliacs. Dossiers of the data on the clinical trial batch production and clinical trial data were submitted to RPC for approval for regular production and supply, which is in active consideration. The analysis of the data shows 98%, 88.3% and 82%, were the therapeutic response observed in clinical conditions: Hemophilia, Rheumatoid arthritis and Osteoarthritis and others respectively. Plans are on the track to undertake the production on regular basis and supply this new therapeutic radiopharmaceutical drug formulation, at an affordable cost.
Optimal Timing of Bisphosphonate Therapy in Combination with Samarium-153 Therapy in Metastatic Bone Disease
N. Rasulova, V. Lyubshin, D. Arybzhanov, A. Amirkhamzaev, M. Pirnazarof, V. Krylov, M. Khodjibekov
Department of Nuclear Medicine, Republic Specialized Center of Surgery, Tashkent, Uzbekistan
Objective: To compare different regimen of widespread bone metastases treatment by Samarium -153 oxabofore and zolendronic acid.
Materials and Methods: Group I: 39 patients (32 female and 7 male, aged 35-71, mean age 54,4+8.0) with multiple skeletal metastases from prostatic carcinoma (7) and breast carcinoma (32) were studied. This group of patients received zolendronic acid 7 and more days prior to Sm-153 oxabifore treatment. Group II: 32 patients all (21 female and11 male, age 38-72, (mean age 57.1+9.7) with multiple skeletal metastases from prostatic carcinoma (10) and breast carcinoma (20) and kidney's cancer (1) were studied. This group of patients received zolendronic acid 48-72 hours prior to Sm-153 oxabifore treatment. Group III: 22 patients (20 female and 2 male, age 29-66, mean age 53+10.3) with bone metastases from breast carcinoma (19), prostatic carcinoma (1) and gastric carcinoma (1). In this group patients received zolendronic acid 7 days after Sm-13 oxabifore treatment. Sm-153 oxabifore was administered to all patients at the standard bone palliation dose of 37 MBq/kg body weight. All patients received zolendronic acid before and after treatment in standard dosage 4mg every 28 days. WB bone scan, CT and MRI were performed before treatment in all patients as well as recording of pain relief occurrence were studied.
Results: In group I: Pain relief occurred in 10.4 +3.1 days (min-5, max-15) after Sm-153 oxabofore administration. Transient flare effect of pain was occurring in both cases: after zolendronic acid and after Sm-153 oxabifore administration. In-group II: pain relief occurred in 3.1 +1.1 days (min-1, max-5) after combined therapy. In most of the patients transient flare effect of pain were occurring after zolendronic acid administration and not after Sm-153 oxabifore administration. In group II: pain relief occurred 22 +5.1 days (min-15, max-35) after combined treatment. Transient flare effect of pain in this group was occurring twice: after Sm-153 oxabifore administration and after administration of zolendronic acid. There was statistically significant difference according in time to pain relief between in all groups of patients P< 0.0001.
Conclusion: According to our examination the most favorable regimen was in the second group of patients: administration of zolendronic acid 48-72 hours prior to Sm-153 oxabifore treatment which gives the most shorter time to pain relief onset. However more deep analysis to understand such effect is needed.
Evaluation of P-32 for Bone Pain Palliation in Prostate Cancer with Skeletal Metastases
M. A. Khan, J. Irfanullah, M. S. Afzal
Nuclear Medicine, Nuclear Medicine Oncology and Radiotherapy Institute (NORI), Islamabad, Pakistan
Objective: The role of phosphorus-32 (32P) was evaluated in patients experiencing pain due to skeletal metastases from prostate cancer and refractory to other modes of treatment.
Materials and Methods: fourteen patients received 185 MBq (5 mCi) P-32 intravenously; 10 patients received a single dose and four patients were injected twice at 3-month intervals. Clinical assessment for bone pain, tender sites, mobility and analgesic intake and blood counts were performed before and 4, 8 and 12 weeks after the administration of P-32.
Results: Results showed a significant decrease in pain intensity at 4 weeks and a palliative response persisted for up to 12 weeks. Analgesic medication intake decreased significantly (P < 0.05) and mobility improved after therapy. Transient myelosuppression was noted after 4 weeks, which was statistically significant for WBC and platelet counts only (P < 0.05), returned within normal limits by 8 weeks.
Conclusion: P-32 is an effective and safe therapy for pain palliation in metastatic prostate disease refractory to other treatments.
Does Clinical Outcome in Hepatic Y-90 Microsphere Therapy Depends on Correlation Between Y-90 and Tc-99m MAA Distributions?
K. Knesaurek, J. Machac, S. Heiba, M. Jiang, Z. Y. Zhang
Radiology/Nuclear Medicine, Mount Sinai Medical Center, 1 G. Levy Pl., New York, USA
Objectives: The purpose of our study was to explore the influence of the correlation between Y-90 and Tc-99m macroaggregated albumin (MAA) distributions on clinical outcome in hepatic Y-90 microsphere therapy.
Materials and Methods: 93 patients, mean age 62 ±11 (mean ±SD) with unresectable primary or metastatic hepatic tumors underwent Y-90 SIR-Spheres® therapy. The prescribed Y-90 activity and the percentage of shunting to the lungs were determined by SPECT/CT MAA imaging and using the body surface area method. A shunt of less than 20% was considered suitable for SIR-Sphere injection. In MAA study activity of 185 MBq was used. Y-90 SPECT/CT was performed 2-4 weeks later and activities used were in the range of 777-2442 MBq. The Y-90 is a pure beta emitter and can be imaged by Bremsstrahlung. In order to compare Y-90 and MAA SPECT images, first the respective CT image sets were registered using a transform based on normalized mutual information. The transform thus derived was used to align the Y-90 and MAA SPECT image sets. The Spearman's (rho) rank correlation between the registered SPECT images was then calculated in order to determine correlation between Y-90 and MAA distributions in SPECT images. The response to Y-90 therapy was assessed by CT (or MR) and/or tumor markers and was categorized as complete response (CR), partial response (PR), progression of disease (PD) and stable disease (SD).
Results: For CR, PR, PD and SD group results for correlation between Y-90 and MAA distributions were 0.59±0.10, 0.59±0.11, 0.60±0.14, and 0.59±0.15, respectively, and expressed as mean ±SD.
Conclusions: Our results indicates that clinical outcome in hepatic Y-90 microsphere therapy does not depend on correlation between Y-90 and MAA distributions.
90Y and 177Lu - Radionuclides for Peptide Receptor Radionuclide Therapy
P. Dariusz, K. Marcin, S. Iwona, M. Anna, M. Renata
Radioisotope Center, Institute of Atomic Energy POLATOM Otwock, Poland
Aim: High specific activity radionuclides are needed for preparation of therapeutic doses of peptide based radiopharmaceuticals for receptor mediated targeting. In addition, other parameters such as radionuclide impurities and chemical impurities may have significant influence on labeling yields and patient safety. The experience with preparation of therapeutic doses of 90Y-DOTATATE and 177Lu DOTATATE in Poland using locally produced 90Y (n.c.a.) and 177Lu (c.a.) is presented.
Materials and Methods: 90Y was produced by solid phase extraction from parent 90Sr and 177Lu was obtained by neutron irradiation of 176Lu enriched targets at the neutron flux of around 2×1014 ncm -2 s -1 in the research reactor Maria in Swierk, Poland. Both radionuclides were obtained as chlorides in 0.05 M HCl. Chemical purity of 90Y and 177Lu was prior evaluated by ICP-OES and radionuclidic purity was assessed by g-spectrometry and LSC for determination of 90Sr. The dried kits containing 100 μg [DOTA-Tyr3-octreotate] (piChem, Austria) and 50.0 mg of commercially available ascorbic acid were prepared under aseptic conditions. For labeling the content of each kit vial was dissolved in not more than 0.5 ml of 90Y n.c.a. chloride of desired radioactivity (typically up to 6.5 GBq (175 mCi) per kit) or 2.8 GBq (75 mCi) of 177Lu c.a. (specific activity of around 555 GBq/mg Lu) chloride solution. Incubation was carried out at 95oC for 25 minutes. The preparation was sterilized by filtration using 0.22 μm filters (Millipore) to sterile glass vials followed by filter wash with 50 mg/ml ascorbic acid to the final radioactive concentration of 740 MBq/ml. The radiochemical purity RCP was assessed by HPLC (column: Synergy 4 Fusion RP 80A 150×4,6 mm, flow rate 0.6 ml/min, UV detection at 220 nm and radiometric detection, solvent A - 0.1 % TFA in water, solvent B - Acetonitrile, gradient: 0 min 18% B; 9 min 60% B; 12 min. 60% B; 15min 18 % B, 21 min 18 % B) and SepPak C-18 (Waters) minicolumn separation according to supplier instruction. The limit for RCP was > 99.0% for each 90Y and 177Lu labeled DOTATATE.
Results: The specific activity of 90Y was > 1.85 TBq/mg Y (500 Ci/mg Y) (non carrier added) and for 177Lu > 555 GBq (15 Ci/mg Lu) at the day of peptide labeling. The contamination with chemical impurities i.e. Zn and Fe were in case of 90Y < 0.27 μg/GBq 90Y (10 μg/Ci 90Y) and in case of 177Lu < 0.027 μg/GBq 177Lu (1 μg/Ci 177Lu). The radionuclidic impurities in 90Y were < 2.5×10-4% (contamination with 90Sr) and in 177Lu <2×10-2% (the contamination with 177mLu). The specific activity of 90Y-DOTATATE was in the range from 45.2 to 137.8 GBq/μmol (median 95.14 GBq/μmol), and for 177Lu-DOTATATE it was from 26.8 to 77.7 GBq/μmol (median 44.17 GBq/μmol). Radiochemical purity (HPLC) was well over 99.0 %, in only one case the RCP obtained for 177Lu-DOTATATE was 98.88%. The total labeling yield calculated as the ratio of radioactivity obtained in the final product to the radioactivity taken for labeling was in the range from 95.01% to 98.98%, average 96.99%. 90Y-DOTATATE and 177Lu-DOTATATE was ready for further use while the mixed doses of 90Y/177Lu-DOTATATE were prepared by drawing the suitable volumes of each 90Y and 177Lu-labelled DOTATATE solutions (1:1 GBq/GBq) with the syringe. The therapeutic doses prepared in this way were used in clinical trial aimed at comparison of results and side effects of PRRT with 90Y-DOTATATE and mixed 90Y/177Lu-DOTATATE.
Conclusion: The therapeutic doses of 90Y- and 177Lu-DOTATATE prepared using n.c.a. 90Y and c.a. 177Lu were suitable for clinical application. The idea of the combination treatment with high-energy 90Y and the low-energy 177Lu has been shown to be bringing positive clinical results in terms of longer mean time of survival in the group of patients treated with 90Y/177Lu DOTATATE.
Early Prediction of Tumor response in GEP NET by the Sequential Change of Absorbed Doses During Treatment with Lu177-Octreotate
S. Ezziddin, A. Damm, C. Yong-Hing, H. Ahmadzadehfar, S. Guhlke, A. Sabet, J. Risse, H. J. Biersack, K. Reichmann
Nuclear Medicine, University Hospital Bonn, Germany
Introduction: [177Lu-DOTA0,Tyr3]-octreotate (177Lu-octreotate) used for peptide receptor radionuclide therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study was to compare tumor and non-tumor parameters and assess intra-individual variations.
Materials and Methods: Consecutive dosimetry of 70 treatments in 29 GEP NET patients, PRRT with 7.53 ±0.46 GBq 177Lu-octreotate (177Lu, IDB Holland), intended 4 cycles at intervals of 3 months (10-14 weeks); standard nephroprotection. Response assessment (CT/MRI) 3 months post-treatment. Dosimetry with serial whole-body imaging (7 time-points), on selected, non-superimposed tumor and non- tumor regions; liver (LM), bone (BM), and other (OM) metastases. Dose calculation with OLINDA after mono-exponential curve fit, comparison of per-cycle variation and correlation with post-treatment response.
Results: Residence time in tumor lesions (LM, BM, OM; 141.0 - 150.2 h) exceeded that in kidneys (92.3 h). Tumor-to-kidney absorbed dose ratios ranged between 27.2±34.0 (LM) and 9.1±4.3 (OM). Intra-individual per-cycle dose variation was insignificant for kidneys (P=0.52), but significant for metastases (LM, BM, and OM; P<0.05). The mean per-cycle decrease of tumor-absorbed dose (ΔD/A0 [%]) was linked to morphologic response after PRRT. A mean decrease of >20% was predictive of a partial or minor remission in 94.4%, while absent significant dose reduction indicated stable or progressive disease in 87.5% of lesions. The dose decrease was unrelated to volume effects and also observed for BM.
Conclusion: Besides confirmation of a favorable tumor-to-kidney parameter relation for 177Lu-octreotate, stepwise intra-lesional comparison demonstrates a prognostic impact of tumor dosimetry: The early per-cycle change ΔD/A0 between treatment cycles predicts the outcome after PRRT.
Effect of Peptide Receptor Radionuclide Therapy with Tandem Isotopes- 90Y/ 177Lu-DOTATATE in patients with Disseminated Neuroendocrine Tumors Depending on Qualification with PET/CT using 18FDG
J. Kunikowska, L. Królicki, D. Pawlak, R. Mikołajczak
Department of Nuclear Medicine, Medical University of Warsaw, Warsaw, Poland
Introduction: Peptide Receptor Radionuclide Therapy (PRRT) using radiolabelled somatostatin analogue is a new treatment modality for inoperable or disseminated neuroendocrine tumors (NET) with Ki-67 below 30 %. Grading is based on primary tumors, but metastatic lesions could have higher Ki-67. Based on the literature, typically high-grade tumors over express somatostatin analogues and don't characterize increase uptake of 18FDG. The aim of the study was to observed response to the tandem 90Y/177Lu-DOTATATE therapy in patients with over expression somatostatin analogues with and without increasing 18FDG uptake before therapy.
Materials and Methods: 34 patients with disseminated NET were included in the study prospectively. 18 of them before treatment underwent PET-CT 60 minutes after 300-370 MBq 18FDG injection and 60-80 minutes post injection of 120-185 MBq 68Ga - DOTATATE on scanner Biograph 64 TruePoint (Siemens Medical Solutions). The period between both studies was no longer than 4 weeks. The administered activity was based on 1:1 90Y/177Lu DOTATATE 3.7 GBq/m2 body surface area in 3-5 cycles, with amino-acids infusion for nephro-protection. Blood tests for hematology, kidney and liver function, and CgA were evaluated before therapy. Median period between the treatments was 49 days.
Results: At the time of treatment all patients showed progressive disease confirmed by CT examination, somatostatin receptor imaging and/or increasing blood concentration of chromogranin A (CgA). Ki-67 of primary tumors in examined group was bellow 20%. 18FDG was positive in 7/18 patients: 3 patients presented 18FDG uptake in all metastases, 2 in part and 2 only in one focus. 11 patients had negative 18FDG study. In all treated group the median overall survival (OS) time was 49.8 months, and time to progression (TTP) was 24.2 months. Time to progression (TTP) was 11.7 months in patient's 18FDG positive and it was not reached 18FDG negative. The median overall survival (OS) time in both groups was not reach. In group with 18FDG positive, 57 % showed progression after PRRT. All patients with 18FDG positive uptake in all metastases showed progression - 6, 12 and 18 months after completed therapy. 1 patient with uptake of 18FDG only in one focus progressed 13 moths after therapy. In group with 18FDG negative study, 18 % showed progression after PRRT- 7 and 19 months after therapy.
Conclusions: The results indicate that tandem radioisotopes (90Y/177Lu DOTATATE) therapy is a safe treatment option for patients with disseminated or inoperable neuroendocrine tumors. 18FDG PET/CT is an additional useful tool for qualifying patients to PRR but it needs longer time of observation. Patients with 18FDG positive uptake in all metastasis needs very careful follow-up, because progression is observed in short time.
Tc-carbonyl Based Octreotide Derivatives
S. Guhlke, T. Guhlke, A. Maylahn, H. J. Biersack
Nuclear Medicine, University of Bonn, Bonn, Germany
Objectives: Various radiolabelled Octreotide analogs in especially DOTA-conjugates are in clinical use for diagnostic and therapeutic applications. In especially Ga-68 labeled peptides including Octreotide derivatives are gaining significant importance for PET-based diagnostics. In case of therapeutic applications Lu-177 and Y-90 labeled Octreotides are used successfully. For SPECT imaging, Tc-99m-Hynic based analogs or In-111 labeled Octreoscan are also available. However, for the diagnostic/therapeutic matched pair Tc-99m/Re-188 relatively little work has been published recently with respect to Octreotide analogs, although the generator nuclide Re-188 offers comparatively very cost effective and on demand nuclide availability. In this work we have therefore followed the idea to combine the well-known favorable influence of DOTA conjugation on the biodistribution of Octreotide analogs with the advantages of the carbonyl labeling approach for stable labeling with either Tc-99m or Re-188. Two custom synthesized Octreotide analogs modified for carbonyl labeling and DOTA-conjugation with the sequences H-D-His-D-Lys (Dota)-D-Phe-Cys-1-NaI-D-Trp-Lys-Thr-Cys-L-Thr (ol) (Disulfide bridge; peptide A), thus a NOC derivative and Dota-D-Lys (Pic)-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr (ate) (Disulfide bridge; peptide B) have been used in the context of these studies.
Materials and Methods: The N-terminal extension by D-His-D-Lys (Dota) on Peptide A allows for Tc-99m or Re188-carbonyl labeling with the Tc99m (CO) 3(H 2 O) 3 aqua ion at D-His. In case of Peptide B, the Dota-D-Lys (Pic) allows carbonyl labeling on the picolinylacetate moiety. Radiolabeling via Tc-carbonyl kits was usually performed on the final deprotected peptide analogs. The radiolabelled analogs were purified by HPLC or SPE and subsequently used for the biodistribution studies at 1,4 and 24 h p.i. using either tumor free or AR2J-tumor bearing nude mice. In order to allow comparison of the new analogs the well known Lu-177-DOTA-octreotate was used as standard in the biodistribution studies, which were performed as dual-isotope studies.
Results: Gradient HPLC studies (not shown) (RP-18; 0.1% TFA vs. MeCN) revealed the following list of increasing lipophilicity: Lu-177-DOTA-Octreotate very similar to DOTA-Lys (Pic-Tc (CO) 3)-Octreotate and with higher lipophilicity Tc (CO) 3-His-Lys (DOTA)-NOC. Biodistribution for peptide A, labeled at the His position was distinctly different from the other peptides which were relative similar for the Dota-Pic and the Lu-177-Dota-tate peptides. The main biodistribution characteristics of the Tc-carbonyl peptide A were hepatobiliary excretion and relatively strong retention in other organs especially in the lungs. The main characteristics of the peptide B (Tc-carbonyl labeled at Pic) were a clear renal excretion and a relative low retention in all other organs except stomach, which may also bear somatostatin receptors. The general biodistribution was very close to that of Lu-177-Dota-tate, which however showed a higher tumor uptake at earlier time points.
Conclusion: The biodistribution characteristics of the Tc-carbonyl labeled peptide A (at His) are clearly inferior to the compared Lu-177 analog. We assume the remaining water ligands on the Tc-carbonyl core and the overall higher lipophilicity of this Tc-analog might have caused the relative unfavorable biodistribution pattern. Even the DOTA-conjugation could not compensate this drawback. The Dota-Pic analog (peptide B, however showed quite interesting results: The biodistribution characteristics of this Tc-carbonyl labeled peptide were very close to that of Lu-177-Dota-tate and showed high tumor uptake as well. Only at early time points tumor uptake was somewhat lower. Further studies are therefore required to fully evaluate the potency of this Tc-labeled peptide and it΄s possible Re-188 labeled analog.
Detection of Activated Microglia with Translocator Protein (18 kDa) Ligand, [18F] FEPPA PET
H. Toyama, K. Hatano, H. Hatano, G. Kudo, M. Nomura, A. Wilson, M. Ichise, M. Sawada, K. Ito
Department of Radiology, Fujita Health University, Toyoake, Japan
Objectives: Activated microglia exists in two functionally different states, cytotoxic and protective states. The former is referred to as a 'fully activated form'. It is worthwhile to distinguish between the two states for diagnosis and treatment. However, there is no reliable method to evaluate the different states. Activated microglia is known to increase the expression of translocator protein (18 kDa) (TSPO), formerly called the peripheral benzodiazepine receptors. A TSPO ligand, [11C] PK11195, suffers low brain uptake and specific binding. We evaluated if a novel TSPO ligand, [18F] FEPPA can detect 'fully activated microglia' in comparison with tyrosine hydroxylase (TH) stain and inflammatory cytokines in a rat 6-hydroxydopamine (OHDA) model.
Materials and Methods: Under anesthesia, 6-OHDA was injected into the rat right striatum (ST). On day 4, PET imaging was performed for 60 min after injection of [11C] PK11195 and then [18F] FEPPA under anesthesia. Seven 6-OHDA rats were then euthanized and immunohistochemical staining (TH) and RT-PCR for inflammatory cytokines (TNFα) was performed for confirmation of the cytotoxic damage. Right/left ST [11C] PK11195 and [18F] FEPPA uptake ratios were evaluated.
Results: TH staining ratios showed significantly negative correlation with [18F] FEPPA PET ratios (r2=0.77, P<0.05). TH staining ratios tended to correlate negatively with [11C] PK-11195 ratios. TNFα ratios showed significantly positive correlation with [18F] FEPPA PET ratios (r2=0.64, P <0.05). TNFα ratios also showed a positive correlation with [11C] PK11195 PET ratios. However, [18F] FEPPA PET and TNFα were more closely correlated.
Conclusions: [18F] FEPPA appears a promising alternative to [11C] PK11195 for PET brain imaging of 'fully activated microglia'.
FDG Uptake, Glucose Transporter Type1 and KI-67 Expressions in Non-small Cell Lung Cancer: Correlations and Prognostic Values
X. C. Nguyen, W.W. Lee, S. Y. Park, S. W. Sung, Y. K. Kim, Y. So, D. S. Lee, J. K. Chung
Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
Purpose: FDG uptake mediated by glucose transporter type 1 (Glut-1) and tumor proliferative activity assessed by Ki-67 expression provide prognostic information in patients with non-small-cell lung cancer (NSCLC). Here, we compared the prognostic significances of FDG uptake, and of Glut-1 and Ki-67 expressions in patients with NSCLC.
Materials and Methods: NSCLC patients (n = 53, F:M= 16:37, age 61.9±12.1 years) who underwent curative resection after FDG-PET were enrolled. Thirty one patients had stage I, 15 stage II, and 7 stage III disease. Patients were treated by surgery only (n = 12), surgery plus adjuvant oral chemotherapy (n = 32), or surgery plus adjuvant intravenous chemo- or radio-therapy (n = 9). Maximum standardized FDG uptake values (maxSUV), and the Glut-1 and Ki-67 expressions of resected tumors were analyzed for correlations and relations with tumor recurrence. The median follow-up duration was 15 months.
Results: Thirteen (24.5%) of the 53 patients experienced recurrence during a median follow-up of 8 months and significant correlations were found between maxSUV, Glut-1, and Ki-67 expressions (r = 0.48-0.79, P < 0.001). Univariate analysis revealed that disease-free survival (DFS) was significantly correlated with maxSUV (<7 versus ≥7, P = 0.001), % Ki-67 expression (<25% versus ≥25%, P = 0.047), tumor size (<3 cm versus ≥3 cm, P = 0.027), and tumor cell differentiation (well/moderate versus poor, P = 0.011). However, multivariate Cox proportional analysis identified maxSUV as the only determinant of DFS (P = 0.005). Patients with a maxSUV of ≥7 (n = 14) had a significantly lower 1-year DFS rate (57.1%) than those with a maxSUV of <7 (n = 39, 89.7%).
Conclusion: FDG uptake is more valuable than Glut-1 or Ki-67 expression in terms of predicting prognosis in patients with resected NSCLC.
Early Response Assessment in Gastrointestinal Stromal Tumors With FDG PET Scan 24 Hours After a Single Dose of Imatinib
A. Shinto, N. Baghel
Nuclear Medicine and PET, KMCH CBE, India
Introduction: Gastrointestinal stromal tumors (GISTs) can demonstrate impressive metabolic response to the targeted molecular therapeutic drug Imatinib mesylate, very early in the course of treatment. Initial reports suggest a substantial role for 18F-FDG PET in follow-up of therapy for these tumors. However, the precise time after initiation of therapy where 18F-FDG PET is to be used to assess or predict response has not been definitively established. We report results from a pilot study aimed at assessing early response in gastrointestinal stromal tumors to a single dose of Imatinib within 24 hours of therapy initiation.
Materials and Methods: The study included 23 untreated, newly diagnosed patients with GIST, who underwent a baseline 18F-FDG PET scan immediately before initiation of Imatinib mesylate therapy. All the patients then underwent repeat scans 24 hours after initiation of therapy. The numbers of sites and SUV max of organs containing lesions on 18F-FDG PET scans were compared between the baseline and 24 hour scans. Corresponding lesions on baseline 18F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on histopathology were considered true positives. Lesions seen on 18F-FDG PET scan but not seen with other imaging modalities or confirmed to be of benign appearance or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on 18F-FDG PET scans were used for quantitative evaluation of early tumor response to therapy. Repeat scans at 24 hours after therapy were assessed for changes in the SUV max in the lesions or sites described on the baseline scan. The patients were then classified as responders, showing greater than or equal to 10 % decrease in SUV max or non responders with no or less than 10 % decrease in SUV max. These patients were then administered the standard therapy with Imatinib Mesylate according to the institutional protocol and subjected to clinical and imaging follow- up. The mean follow- up duration was 12-14 hours.
Results: A total of 56 true positive sites and/or organs were involved on pretherapy 18F-FDG PET scan in the 23 patients; which were compared with the 24 hour post therapy initiation scan. The sensitivity and positive predictive values (PPVs) for 18F-FDG PET at baseline were 96% and 98%. The criteria for partial response on FDG PET (10% reduction in PET SUVmax) at 24 hours in 21patients (P = 0.004) were predictive of prolonged treatment success. The two patients demonstrating no significant change in SUV max post therapy did not demonstrate good response to Imatinib therapy on follow up. These findings suggest that 18F-FDG PET at baseline and 24 hours post -therapy initiation could be useful in early prediction of response or primary resistance to Imatinib therapy in primary GIST patients. Conclusion: The performance of 18F-FDG PET at baseline and 24-hour post initiation of therapy with imatinib mesylate could be a guide to predict treatment response. Early 18F-FDG PET scan at 24 hours could be a potential tool to identify primary resistance to therapy at a very early stage of patient management and therapy.
Potential Use of 177Lu in Radioimmunotherapy as Targeting Tracers on Monoclonal Antibodies
S. J. Choi, S. Y. Lee, Y. D. Hong
Basic Science and Technology, Korea Atomic Energy Research Institute, Daejon Republic of Korea, Korea
The main goal of this study was to optimize the radioimmuno-conjugation of monoclonal anti-vascular endothelial growth factor receptor-1 (VEGFR-1) and anti-CD105 (Endoglin) monoclonal antibody for angiogenesis targeting with 177Lu as a potential angiogenic molecular tracer in Radioimmunotherapy. In order to develop a more useful marker than conventional panendothelial ones in identifying proliferating endothelium involved with tumor angiogenesis, radioimmuno-conjugation using 177Lu with anti-CD105 (Endoglin) and with anti-VEGFR1 was carried out. By using cysteine derivative isothiocyanatobenzyl-DTPA (DPTA-NCS) as BFCA, the labeling of monoclonal antibody with 177Lu was optimized by performing the experiment under the optimal conditions, with slight modifications on factors such as reaction time and molar ratio, which are known to be very critical in radiolabeling. The resulting labeling yield was greater than 99% for both the anti-VEGFR-1 and anti-CD105 monoclonal antibodies. Immunoactivity of the radioimmuno-conjugate was investigated using combinations of radioanalytical and bioanalytical techniques, such as ITLC-SG, Cyclone phosphor imager, SDS-PAGE and ELISA. For biological investigations, a cell binding assay and a biodistribution study was carried out using Calu-6 lung cancer cell xenograft implanted mice. 24 hours after injection, the tumor to blood ratio was 11.16:1 for anti-CD105. Using the same 24 hour post-injection period, for anti-VEGFR1, the biodistribution study showed higher specificity in accumulating within tumor tissues and the tumor to blood ratio was 3.25:1. In conclusion, both anti-VEGFR1 and the anti-CD105 monoclonal antibody was effectively radio-conjugated with 177Lu for angiogenesis targeting and the biodistribution study showed high specificity for accumulation within tumor tissues. The use of anti-CD105 monoclonal antibody as a radioimmuno-conjugate range from being able to detect angiogenesis sites in various diseases to treating tumors. Applications of the anti-VEGFR1 monoclonal antibody radioimmuno-conjugate are to detect angiogenesis sites in various diseases and to treat tumors containing over-expressed VEGFR-1.
Effect of Molecular Imaging on Evaluation of the Therapeutic Efficacy of VEGFR2 Blocking Antibody in a Sodium-iodide Symporter Gene Expressed Tumor Model
S. J. Cheong, C. M. Lee, D. Jang, E. M. Kim, M. H. Jeong, D. W. Kim, S. T. Lim, M. H. Sohn, H. J. Jeong
Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, South Korea
Purpose: Vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted tumor therapy is an effective anti-angiogenic strategy. The human sodium/iodide symporter (hNIS) gene is a useful reporter gene for tumor imaging and radiotherapy. In this study, we investigated the potential of molecular imaging to evaluate the therapeutic efficacy of VEGFR2 blocking antibodies on hNIS-transfected tumor models.
Materials and Methods: The correlation between the number of hNIS-transfected MDA-MB-231 cells and the uptake of 99mTc-pertechnetate or 125I was investigated in vitro by gamma imaging and counting. To generate xenografts, MDA-MB-231-hNIS cells were injected subcutaneously into mice. VEGFR2 blocking tumor therapy was initiated when the tumor volume reached approximately 130-180 mm 3. The antibodies were injected intravenously through the tail vein of the mice at 50, 100, or 150 μg/dose every 3 days for 16 days. One week and 2 weeks after the first injection of the antibodies, micro-single photon emission computed tomography (SPECT)/computed tomography (CT) imaging was performed to monitor the effects of the antibodies in tumor therapy. Mice were sacrificed 2 weeks after the first injection of the antibodies and the tumors were removed for RT-PCR and CD31 staining.
Results: Uptake of 125I and 99mTc-pertechnetate into MDA-MB-231-hNIS cells showed high correlation with the number of cells in vitro. In all of treatment groups, the antibodies reduced tumor growth compared to the control group. In vivo SPECT/CT imaging results showed that tumor uptake of 125I in the mice treated with the antibodies was lower than in the control group. CD31 staining and RT-PCR analyses indicated that blood vessel formation and expression of the hNIS gene were reduced in the tumor tissues of treatment group. Conclusion: This study demonstrated the feasibility of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of anti-tumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.
Diagnostic Efficacy of Scintimammography for the Detection of Malignant Tissue in the Breast Performed with Tc99m-MDP and Tc99m-Sestamibi
B. K. Das, P. K. Pradhan, S. Deswal
Department of Nuclear Medicine and Imaging Sciences, Utkal Institute of Medical Sciences, Bhubaneswar, India
Introduction: Breast cancer has been found to be the first cause of cancer death in women in urban areas in India. Most patients come in stage II and above, many times delayed due to absence of a definitive diagnostic procedure. X-ray mammography and other imaging modalities lack in specificity in comparison to recently introduced Scintimammography (SMG), which is performed using Sestamibi or Tetrofosmin. Efforts have been made to use MDP in place of Sestamibi which is otherwise used for bone scanning and is significantly cheaper and has also the advantage of obtaining bone scan on the same day in one go The purpose of this study is to compare the efficacy of both agents.
Materials and Methods: 123 consecutive patients with confirmed diagnosis of breast cancer clinically and histo-pathologically were subjected to Scintimammography using 20 mCi of Tc99m-MDP (BRIT, BARC, Mumbai) and a dual headed gamma camera using standard technique. Scintimammography was performed in another 105 consecutive similar patients using the same standard technique and equipment but with Tc99m-Sestamibi (Sanlar). 30 patients clinically suspected of having breast cancer and later confirmed were subjected to SMG using both agents on two separate days. Each scan was evaluated by two nuclear physicians. Ratio of tracer uptake in the lesion and normal tissue was calculated.
Results: Sensitivity and specificity was found to be 96.9 % and 92.2 % respectively in patients performed with Tc99m-MDP and 98.1 % and 93.7 % respectively in patients using Tc99m-Sestamibi. Out of 30 cases in which SMG was performed using both agents, 28 (93 %) showed concordant findings (both positive 16, both negative 12). In two patients Sestamibi scans were positive but MDP scans were negative. In 16 MIBI positive cases 3 showed concentration in axillary lymph nodes which was not seen in MDP scan. In 16 MDP positive cases 4 showed metastatic involvement of the skeletal system. The activity ratio in MIBI and MDP scans was similar and varied from 1.3 to 5.7. In one case a small lesion in the other breast was not visualized in MDP scan.
Conclusions: The sensitivity and specificity found in our studies is higher than in many multi-center studies which may be due to the fact that most patients were in stage II and higher at the time of diagnosis. Tc99m-Sestamibi is potentially better than Tc99m-MDP in detection of malignant lesions. However, MDP is not only cheaper, but the whole body bone scan, which can be performed in one sitting, can provide vital information regarding metastatic involvement of the skeletal system. Tc99m Sestamibi remains the choice radiopharmaceutical for early diagnosis of breast cancer. However, Tc99m-MDP can be recommended for diagnosis of breast cancer in cases suspected to be in stage II and higher with the additional benefit of getting vital information regarding involvement of skeletal system.
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