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ABSTRACT
Year : 2011  |  Volume : 10  |  Issue : 1  |  Page : 90-97

Abstracts of Poster Presentations (Ga-68 Imaging)


Date of Web Publication16-Jun-2011

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How to cite this article:
. Abstracts of Poster Presentations (Ga-68 Imaging). World J Nucl Med 2011;10:90-7

How to cite this URL:
. Abstracts of Poster Presentations (Ga-68 Imaging). World J Nucl Med [serial online] 2011 [cited 2019 Aug 21];10:90-7. Available from: http://www.wjnm.org/text.asp?2011/10/1/90/82110

P-031

Role of Ga-68 Somatostatin Receptor PET/CT in the Detection of Unknown Primary Neuroendocrine Tumors

Vikas Prasad 1 , U. Settmacher 2 , Merten Hommann 3 , Daniel Kaemmerer 3 , Dieter Hoersch 4 , T. Bert 4 , Richard P. Baum 1

1 Department of Nuclear Medicine and Centre for PET/CT, Zentralklinik Bad Berka, Germany; 2 Department of General and Visceral Surgery, University Hospital, Jena; 3 Department of General and Visceral Surgery, Zentralklinik Bad Berka, Germany; 4 Department of Internal Medicine/ Gastroenterology, Oncology and Endocrinology, Zentralklinik Bad Berka, Germany

Aim: Ga-68 Somatostatin-Receptor PET/CT (Ga-68 SMS-R) has been shown to be imaging method of choice for detection of unknown primary neuroendocrine tumor in our previous bicentric study. The aim of this study was confirm the results in a larger group of patients and to look into the possible reasons for the false negative findings of Ga-68 SMS-R PET/CT.

Materials and Methods: Overall 124 patients having neuroendocrine tumor of unknown primary (defined as no evidence of primary on the conventional morphological imaging) were included in this study. Ga-68 SMS-R PET/CT was performed for staging or restaging according to the guidelines published by the European Association of Nuclear Medicine (EANM). In addition MRI, CT-Abdomen, Ultrasound Abdomen and Endosonography and F-18 FDG PET/CT was performed wherever needed. The lesions detected on Ga-68 SMS-R PET/CT were confirmed either on follow-up or using other diagnostic modalities.

Results: Histopathological classification was available in 108 patients: 89% (n=94) had well differentiated tumor, 4% (n=5) had moderately differentiated and 6% (n=6) had poorly differentiated tumor while in the remaining 3% (n=3) the tumor was undifferentiated. In 109 patients liver metastases were present, 57 patients had lymph node metastases and 44 had skeletal lesions. Ga-68 SMS-R PET/CT could detect 69 primary tumors (56%) which correspond to our previously reported results (59% detection rate). Histopathological confirmation was available in 12/69 patients. 9 Patients were operated (5 pancreatic, three ileal/jejunum and one rectal tumor) and biopsy was performed in the rest three. The following primaries were detected: pancreas- 33, ileum-25, lung-4, colo-rectum-3, paraganglioma-1, ovary-1 and two patients had gastrinoma in the region of truncus celiacus/pancreatico-duodeno-gastro triangle; one patient had multiple sited of primary in pancreas and small intestine; one patient had MEN-1 syndrome. Proliferation rate was available in 53% (n=66) of the patients. In the patient group in which no primary was detected on Ga-68 SMS-R PET/CT, 43% (n=9/21) of the patients had Ki67 >20%. In 5/6 (83%) poorly differentiated NET, the Ga-68 SMS-R PET/CT was found to be false negative. In this subgroup, F-18 FDG PET/CT could detect the primary in the pancreas in 2 patients. In the undifferentiated / moderately group Ga-68 SMS-R PET/CT could not detect the primary in 3/4 patient (75%). There was no correlation between the SUV max and the proliferation rate. The SUV max in the primary tumors ranged from 3.3-85. Out of 33 pancreatic NETs detected, EUS was performed in 9 patients confirming the findings of PET/CT and additionally detecting. In one patient EUS detected three sites of primary less than 5 mm while PET/CT could detect only 1 of them.

Conclusion: This follow-up study confirm that Ga-68 SMS-R PET/CT is the imaging method of choice for the detection of unknown primary neuroendocrine tumors. Poorly and undifferentiated tumors having proliferation rate greater than 20% are primarily responsible for false negativity of Ga-68 SMS-R PET/CT. In patients with undifferentiated or poorly differentiated NET F-18 FDG PET should be performed to localize the site of primary tumor.

P-032

What Size of Metastases We Could be Missing in 99m Tc Tectrotide SPECT with Comparison to 68 Ga -DOATATE PET/CT in Diagnosis of Patients with Neuroendocrine Tumors?

Jolanta Kunikowska, Leszek Krolicki, Dariusz Pawlak, Renata Mikołajczak


Nuclear Medicine Department, Medical University of Warsaw, Poland and IEA POLATOM, Świerk, Poland

Introduction: Due to knowledge of overexpresion of somatostatin receptors (SSTR) imaging of neuroendocrine (NET) tumors with radiolabeled somatostatin analogs has become common practice. 111In-DTPA-octreotide (OctreoScan® ) and 99m Tc tectrotide scintigraphy are the nuclear medicine imaging modality for identifying neuroendocrine tumors. There are some limitations of those methods - higher physiologic uptake in liver and detection of smaller lesions. Because of better resolution of PET/CT 68 Ga-DOTATATE imaging open new modality tool for NET diagnosis. The aim of this study was to comparison the level size of visualized metastases in PET/CT 68 Ga-DOTATATE and 99mTc tectrotide SPECT in patients with metastatic neuroendocrine carcinoma.

Materials and Methods: 28 (14 men, 14 women; age range, 32-83 y; mean age ± SD, 60.3±13.2 y) patients with disseminated, histologically proven NET were enrolled to the study. All with previous 99mTc tectrotide scintigraphy (planar whole body and SPECT of abdomen using dual-head Varicam camera after 700-800 MBq injection of 99mTc tectrotide) underwent 68 Ga-DOTATATE PET/CT using a Siemens Biograph 64 PET/CT scanner, 60-80 minutes post injection of 120-185 MBq of 68 Ga -DOTA-TATE.Clinical history, previous imaging examinations and treatments were documented.PET/CT findings were compared by region with conventional scintigraphy.

Results: 99mTc tectrotide was negative in 7/28 patients. 68 Ga-DOTATATE PET/CT showed normal uptake in 2/7 and in 5 patients revealed focal uptake in liver 3 cases, bone 3 cases, intestine 1 pts and lymph node in 1 pts. The median size of not visualized lesions was 11 mm (range 6-15 mm). In 21/28 images of both modalities demonstrated focal uptake at multiple sites. 68 Ga-DOTATATE PET/CT images were better resolution and clearer than 99mTc tectrotide images for interpretation. Similar foci were identified with both modalities in 26 regions, with additional foci on 68 Ga-DOTATATE PET/CT 10 (38%) regions. New lesions were seen in bone 4 patients (median size 10 mm, range 7-13 mm), lymph node 4 patients (median size 9 mm, range 5-15 mm) and liver 2 patients (median size 12 mm, range 11-13 mm). In 3 cases 68 Ga-DOTATATE PET/CT clarified focal uptake in abdomen- 1 in pancreas and 2 in lymph node.

Conclusion: Major limitation of 99mTc-tectrotide SPECT is visualization foci lower than 12 mm. The bone and liver metastases is the most missing location in 99mTc-tectrotide. In patients with negative 99mTc-tectrotide SPECT PET/CT with 68 Ga-DOTATATE should be performed.

P-033

Performance of DOTATOC PET/CT for the Detection of Gastrinomas

Françoise Montravers, Valérie Nataf, Aurélie Prignon, Jimmy Rose, Sona Balogova, Khaldoun Kerrou, Virginie Huchet, Odile Pascal, Laure Michaud, Jean-François Grellier, Jean-Noël Talbot


Hôpital TENON, 4 rue de la Chine, F75020 Paris, France

Purpose: The purpose of this study was to evaluate the performance of DOTATOC-( 68 Ga) PET/CT in comparison with Somatostatin Receptor Scintigraphy (SRS) for the detection of gastrinomas.

Patients and Methods: Between February 2008 and February 2011, 15 adult patients were referred for localisation of a suspected sporadic gastrinoma (5 patients), to search for the primary after diagnosis of a lymph node metastasis (1 patient), for localisation of gastrinoma(s) in one patient with Multiple Endocrine Neoplasia type 1 (MEN-1), for suspicion of recurrence (6 patients) or for re-staging of metastatic gastrinoma in 2 patients. DOTATOC PET/CT and SRS were both performed in all patients.

Results: Of the 5 patients suspected of sporadic gastrinoma, the diagnosis was finally excluded in 1 patient (DOTATOC PET/CT and SRS both true negative). One case is still under investigation. Of the 3 patients with confirmed sporadic gastrinoma, DOTATOC PET/CT was true positive (TP) in 2 patients and false negative (FN) in one patient. SRS was TP in one patient and FN in 2 patients.

In the patient referred to search for the primary, DOTATOC PET/CT and SRS were both TP for the detection of the lymph node metastasis but both failed to detect the primary which remained unknown after surgery. - In the patient with MEN-1, DOTATOC PET/CT and SRS were both TP on a per patient basis but DOTATOC PET/CT was superior to SRS, showing multiple gastrinomas in the duodenum and in the pancreas, and several regional tumor lymph nodes, while SRS was positive only for the largest lesions. - In patients suspected of recurrence, DOTATOC PET/CT and SRS were FN in 2 patients. Two patients negative with morphological imaging, DOTATOC PET/CT and SRS are still under investigation. In two patients, DOTATOC PET/CT and SRS were both TP on a per-patient basis but DOTATOC PET/CT was superior to SRS on a per site basis. - In the 2 patients referred for re-staging, DOTATOC PET/CT and SRS were both TP on a per-patient basis but DOTATOC PET/CT showed more lesions than SRS.

Conclusion: In this prelimary series of gastrinomas, the sensitivity of detection of sporadic gastrinomas was 1/3 for SRS and 2/3 for DOTATOC PET/CT. In case of MEN-1 and for detection of recurrences, the sensitivities of SRS and DOTATOC PET/CT were identical (3/5) on a per-patient basis but DOTATOC PET/CT was clearly superior to SRS on a per-site basis.

P-034

Efficacy of Ga-68 Somatostatin Receptor PET/CT and Peptide Receptor Radionuclide Therapy in the Management of Neuroendocrine Tumors of the Rectum

Vikas Prasad, D. Kaemmerer, M. Hommann, D. Hoersch, H. Kulkarni, C. Zachert, R.P. Baum


IZentralklinik Bad Berka, Germany

Aims: To assess the role of Ga-68 somatostatin receptor PET/CT (SR-PET/CT) and Peptide Receptor Radionuclide Therapy (PRRNT) in the diagnosis and treatment in patients with neuroendocrine tumors of the rectum (rNET).

Materials and Methods: 24 patients (Male: Female 13:11; mean age 55.2 yrs) with rNET were referred for staging or restaging with SR-PET/CT and for evaluating the possibility of PRRNT (using Y-90 or Lu-177 DOTATATE). SR-PET/CT was also used for response assessment after PRRNT.

Results: Median duration of follow-up from first cycle of PRRNT was 14.7 months (3-39 months). Sites and numbers of metastases on detected on CT scan alone were the following: liver (15), lymph nodes (9), bone (1) and local recurrences (2). On the other hand SR-PET/CT detected 14 metastases in the liver, 9 lymph nodes, 10 in bone and 2 local recurrences in the same group of patients. Discordant results (SR-PET+ and CT-): bone 9/10 and lymph node 1. In 2 patients, SR-PET was negative and CT positive (1 liver and 1 lung lesion). 19 patients were treated by PRRNT (15 received >3 cycles). In total, 27% of patients achieved a partial remission/minor response, 40% had stable disease, whereas the remaining 33% had progressive disease. 7 patients showed a fall in tubular extraction rate (TER) of greater than 20% (Lu-177: n=3 and Lu-177 plus Y-90: n=4). Out of 7 patients with a TER fall of >20%, 3 had prior external radiation therapy (60 Gy), 2 had 5-FU/streptozotocin chemotherapy, and one patient had diabetic nephropathy and arterial hypertension. Anaemia grade 1-2 occurred in 14 patients (74%), grade 3 in four (21%), and grade 1 thrombocytopenia in one patient (5%).

Conclusions: Ga-68 somatostatin receptor PET/CT is superior to CT alone for staging of rectal neuroendocrine tumors, and especially for the detection of bone metastases. PRRNT is safe and effective in patients with progressive neuroendocrine rectal tumors.

P-035

Title of Presentation: EBUS and Biochemical Analysis in Workup of Cervical Lymph Node Metastasis of MTC, Positive on Ga-68-DOTATATE PET

Koen K. De Vis


Department Nuclear Medicine, AZ Turnhout, Belgium

Aim: Use of new armamentarium in order to obtain exact information about cervical lymph nodes.

Materials and Methods: In the followup of medullary thyreoid cancer (MTC) an increase of the tumor markers (calcitonin and CEA) may indicate locoregional recurrence or distant metastasis. If the rise of the marker is small, conventional imaging often is not contributory. Then molecular imaging with total body Ga-68-DOTATATE PET-CT is a sensitive tool. Suspect cervical lymph nodes in thyreoid cancer usually require fine needle aspiration cytology (FNAC) confirmation. Ultrasound guidance may not be possible for deep cervical nodes. EBUS is an elegant, lowly-invasive technique allowing FNAC of deep cervical paratracheal, especially posterolateral, and lower cervical or mediastinal lymph nodes. Vessels or bony structures may prohibit a percutaneous cytological aspiration. EBUS has a pretty good safety record in intrathoracic malignancies, especially lung cancer. (20 minutes, moderate sedation, local pharyngeal spray anesthesia). Cytological diagnosis of MTC may be difficult. As with thyreoglobulin in lymph nodes of differentiated follicular/papillary thyreoid cancer, a biochemical analysis of the rinsing fluid of the FNAC-syringe might be helpful. We aspirate 1 ml of saline after the emptying of the syringe for the cytological smears. We determine calcitonin and CEA on that fluid. These analyses are of course semiquantitative/qualitative and not quantitative.

Results: Case report: 71-year old male with non-familial left-sided MTC 19 years ago: total thyreoidectomy. A few months later he got a neck dissection (not exactly specified); negative followup for many years. After 17 years resection of an ipsilateral cervical lateral tumoral mass with phrenical nerve palsy. Calcitonin was persistently slightly elevated (60 ng/l) and was rising after 3 months (up to 95 ng/l). On PET-CT with Ga-68-DOTATATE a solitary, ipsilateral, hot, lower cervical, posterolateral, paratracheal lymph node. Percutaneous ultrasound-guided FNAC was technically impossible. With EBUS however, FNAC was quite easy. Immunocytochemistry was positive for chromogranin and calcitonin. The qualitative biochemical analysis of the rinsing fluid of the syringe was strongly positive for CEA and moderately for calcitonin. A minimally-invasive resection of the node was done because it was a solitary focus in a very slowly progressing tumor in an area with 2 previous operations: pathologically confirmed lymph node metastasis of MTC. Postoperative calcitonin dropped to 6.4 ng/l.

Summary: 1. EBUS may add to the workup of cervical (and mediastinal) foci on Ga-68-DOTATATE PET-CT, permitting FNAC of suspect nodes. Cervical nodes may be out of reach for percutaneous ultrasound guided FNAC. The EBUS option evidently applies to suspect cervical findings with other imaging modalities and probably all tumor types. 2. After FNAC the rinsing fluid can be qualitatively tested for MTC markers (calcitonin and CEA). This is a simple test for the presence of nodal metastasis, likewise the search for thyreoglobulin in FNAC of cervical nodes that are suspect for metastasis of follicular/papillary thyreoid cancer. This biochemical analysis especially helps to reduce sampling error in small metastatic foci in a lymph node and when cytological discrimination itself is difficult.

P-036

Comparison of 68 Ga-DOTA-TATE and 68 Ga-DOTA-NOC PET/CT Imaging in the same Patient Group with Neuroendocrine Tumors

Emre Demirci 1 , Meltem Ocak 2 , Levent Kabasakal 1 , Clemens Decristoforo 3, Burçak Güneş1 , Esra Arslan 1 , Ahmet Araman 2, İlhami Uslu1

1Department of Nuclear Medicine, Cerrahpaşa Medical Faculty, Aksaray Istanbul, Turkey; 2 Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, Istanbul, Turkey and 3 Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria

Aim of the Study: The application of 68 Ga-labelled somatostatin (sst) derivatives is becoming of increasing interest for cancer imaging and can be used for positron emission tomography (PET) imaging of tumors expressing sst receptors. Among the all available 68 Ga-labelled sst derivatives, DOTANOC has shown high affinity to sstr-2 and sstr-5, DOTATATE has shown high affinity to sstr-2 in sstr-positive tumors imaging. The aim of our study was to compare the diagnostic value of 68 Ga-DOTA-NOC and 68 Ga-DOTA-TATE in the same patient group with neuroendocrine tumors.

Materials and Methods: All patients had given written informed consent to participation in the study, which had been approved by the local ethics committee. Twenty patients (F/M: 13/7, mean age 55.33±12.65) with a diagnosis of primary or recurrent NET (8 unknown primary metastatic NET, 5 pancreas NET,1 Merkel cell carcinoma, 2 lung carcinoid tumor, 2 gastrinoma, 2 paraganglioma) were prospectively examined. Patients were intravenously injected 148±42 MBq 68 Ga-DOTA-NOC and 68 Ga-DOTA-TATE (which was synthesized by using Fractionated Moduler System with 30 mCi 68 Ga/ 68 Ge Generator, Eckert& Ziegler Eurotope, Berlin, Germany) at least in 8 hours intervals. 30-60 minutes after the injection of radiolabelled peptides, PET/CT images were obtained. PET imagings were obtained with both tracers and compared with each other.

Results: The image quality of 68 Ga-DOTA-NOC was not different than that of 68 Ga-DOTA-TATE PET/CT. With 68 Ga-DOTA-TATE physiological SUV max value of pituitary gland, parotid gland was found significantly higher (p <0.05). In 6 patients (30%) no pathologic uptake was seen with both tracers. The number of lesions detected by PET images with both tracers were not significiantly different (P >0.05). In 2 patients number of detected liver lesions were found higher with 68 Ga-DOTA-TATE. And also in 1 patient with pancreas NET, number of detected lenf node metastases was higher with 68 Ga-DOTA-TATE.

Summary: The results of the present study have suggested that 68 Ga-DOTA-NOC and 68 Ga-DOTA-TATE PET imaging is same in diagnosis sst expressing tumors. However in some tumors which have different subtype of sstr behavior of both 68 Ga-labelled peptides can be different.

Acknowledgement: This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number 3264

P-037

Comparison of 68 Ga-DOTA-TATE and 68 Ga-DOTA-LAN PET/CT Imaging in the same Patient Group with Neuroendocrine Tumors

Emre Demirci 1 , Meltem Ocak 2 , Levent Kabasakal 1 , Clemens Decristoforo 3, İlhami Uslu1

1Department of Nuclear Medicine, Cerrahpaşa Medical Faculty, Aksaray Istanbul, Turkey; 2 Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, Istanbul, Turkey and 3 Clinical Department of Nuclear Medicine, Medical University Innsbruck, Austria

Aim of the Study: 111In-DOTA-lanreotide (DOTA-LAN) have been reported with a high affinity to the somatostatin receptor (sstr) subtypes 2, 3, 4, 5 whereas 90Y-DOTA-LAN have been reported with a high affinity to the sstr subtypes 3,5. And also the comparison of 111In/90Y-DOTALAN with radiolabelled DOTATOC have been showed discordant results in vivo for detection of lesions and tumor uptake. In our study we aimed to compare tumor and organ distribution and visulation of 68 Ga-DOTA-LAN with 68 Ga-DOTA-TATE (characterized by a very high affinity for sstr2) in the same patient group.

Materials and Methods: All patients had given written informed consent to participation in the study, which had been approved by the local ethics committee. 15 patients (F/M: 8/7, mean age 49.8) with a diagnosis of primary or recurrent NET (3 pancreatic NET, 3 carcinoid tumor, 2 NET of unknown primary site, 1 medullary thyroid carcinoma, 1 Merkel cell carcinoma, 1 Insulinoma, 1 meningioma, 1 Periampullary NET, 1 pheochromocytoma, 1 gastrinoma) were prospectively examined. Patients were injected intravenously 125±25 / 122±29 MBq 68 Ga-DOTA-TATE and 68 Ga-DOTA-LAN at least in 8 hours intervals. 30-60 minutes after injection of radiolabelled peptides PET/CT images were obtained. Images were evaluated visually and SUV max value of bone marrow, pituitary gland, parotid glands, liver, spleen, adrenal glands and lesions was calculated.

Results: In 5 patients (33%) no pathologic uptake was seen with both tracers. In 4 patients only (27%) 68 Ga-DOTA-TATE was positive and in one patient (7%) with NET of unknown primary site only 68 Ga-DOTA-LAN was positive. And in 5 patients (33%) pathologic uptake was seen with both radiotracers. SUV max values of lesions with 68 Ga-DOTA-TATE were found significiantly higher than 68 Ga-DOTA-LAN (P<0.05). 68 Ga-DOTA-TATE also demonstrated higher SUV max value for pituitary gland, parotid glands, adrenal glands, liver and spleen (P<0.05). On the other hand bone marrow uptake of 68 Ga-DOTA-LAN was found significantly higher (P<0.05).

Summary: Based on possibly differences in sstr subtype expression, the image quality of 68 Ga-DOTA-LAN was found worse than that of 68 Ga-DOTA-TATE PET/CT with high bone marrow uptake. 68 Ga-DOTA-LAN may be of advantage in certain patient groups with tumors expressing predominantly other receptor subtypes than SSTR2. Our study will continue with in large number of patients.

Acknowledgement: This work was supported by Scientific Research Projects Coordination Unit of Istanbul University. Project number 3264

P-038

Title of Presentation: Effectiveness of PET / CT with 68 Ga-DOTA-d-Phe (1)-Tyr (3)-Octreotide (DOTATOC) Against Conventional Imaging Methods in Neuroendocrine Tumors

Irma Soldevilla Gallardo, GarcíaPérez Francisco Osvaldo, Estrada Lobato Enrique, Patiño Zarco Mario


Instituto Nacional de Cancerología, Avenida San Fernando No. 22 Colonia Sección XVI, México, D.F., C.P. 14080, Mexico

Introduction: The initial assessment of neuroendocrine tumors has been regularly performed using somatostatin analogs labeled with 111In or 99mTc. Nevertheless, the arrival of positron emission tomography has revolutionized the diagnostic-therapeutic approach, due to the increasing in specificity and sensitivity for this molecular imaging modality. The labeling of these new peptides with 68 Ga is considered a high accurate diagnostic study, and it provides a relatively low dosimetry and, as it is obtained by a generator, the availability has been improved.

Aim: To show the initial experience in the use of 68 Ga DOTATOC in patients with neuroendocrine tumors in the Instituto Nacional de Cancerología and compare the effectiveness versus other conventional imaging methods.

Materials and Methods: The study included 27 patients with histopathological diagnosis of neuroendocrine tumor and imaging study for initial evaluation. Then, the restaging and assessment of therapy response were done using 68 Ga-DOTATOC PET/CT. The regions of interest in the normal biodistribution structures and the tumor lesions were drawn. The results were compared to other conventional imaging methods. The verification was carried out by endoscopical or surgical findings with histopathological study.

Results: We studied 27 patiets (19 women and 8 men) with mean age 48 ± 11.7 years old. The 68 Ga DOTATOC PET/CT sensivity was 86% (32/37) and contrasted CT sensitivity was 78% (29/37). 6 patients (4 high-grade, 2 low grade) had supplementary 18FDG PET / CT, showing a statistically significant difference P=0.0442 ( P<0.05). The SUV max range of structures with normal uptake did not show any significant difference in all cases. Three patients with other molecular imaging studies (131I MIBG or 18 F-FDG) did not show the recurrence site, while using the 68 Ga DOTATOC the detection was effectively performed.

Conclusions: It was observed that the 68 GaDOTATOC PET/CT was useful in the evaluation of neuroendocrine tumors. Since it has high sensibility and specificity, it provides additional information not showed in conventional imaging methods. The gained medical impact, showed the advantages of the use of 68 Ga DOTATOC PET/CT in the neuroendocrine tumor evaluation.

P-039

Different Sites of Rare Metastases in Neuroendocrine Tumor Patients Detected by Ga-68 Somatostatin Receptor PET/CT

Vikas Prasad, Harshad Kulkarni, Richard. P. Baum


Zentralklinik Bad Berka, Bad Berka, Germany

Aim: The most common sites of metastases in neuroendocrine tumors are liver, lymph nodes, and bone. The aim of this study was to find out the incidence and location of other sites of metastases.

Materials and Methods: Out of 4210 Ga-68 somatostatin-receptor PET/CT studies have been performed at our centre starting between July 2004 and December 2009. We retrospectively looked into the reports of patients to check the rare sites of metatsases other than liver, bone and lymph nodes. The lesions were confirmed on follow-up and/or other imaging methods (MRI, echocardiograohy, ultrasound)

Results: The different sites of metatsases according to the frequency of occurrence were : cardiac metastases (n=29), breast metastases (n=21), retro-orbital (n=9), uterus (n=7), skin (n=8), brain (n=6), spleen (n=3), testes (n=1), seminal vesicle (n=1), intramuscular in psoas muscle (n=4).

Conclusion: Cardiac and breast metastases appears to be not so in-frequent in NET patient. Ga-68 somatostatin-receptor PET/CT enables detection of these rare sites of metastases.

P-040

Intraoperative Somatostatin Receptor Detection after Peptide Receptor Radionuclide Therapy with Lu-177 DOTATOC in Metastatic Gastroenteropancreatic Neuroendocrine Tumor

Mila Todorović-Tirnanić, Daniel Kammerer1 , Vikas Prasad 2 , Merten Hommann 1 , Richard P. Baum 2


Centre for Nuclear Medicine, Clinical Centre of Serbia and Faculty of Medicine University of Belgrade, 1 Department of Surgery and 2 Department of Nuclear Medicine and Centre for PET/CT, Zentralklinik Bad Berka, Germany

Aim: Presenting the results of the first intraoperative somatostatin receptor detection after peptide receptor radionuclide therapy (PRRNT) with Lu-177 DOTA-TOC and their comparison with the findings of pre-operative Ga-68 DOTA-TOC PET/CT in a patient with metastatic neuroendocrine tumor (NET) of ileum.

Materials and Methods: A 56 years old female patient with Karnofsky index of 90 - 100, who already received 2 PRRNT, was admitted for the third PRRNT and surgery. She was without therapy for three months. Preoperative tumor markers, abdominal ultrasonography, Tc-99m MAG3+TER, Ga-68 DOTA-TOC PET/CT, abdominal magnetic resonance imaging, Tc-99m DTPA+GFR and F-18 fluoride PET/CT were performed. After that patient received the third (TANDEM) PRRNT cycle with 3000 MBq Y-90 DOTA-TOC and 6000 MBq Lu-177 DOTA-TOC. WB scintigrams were performed 23 h and 43 h thereafter. Five days after PRRNT patient was operated and gamma probe was used for guiding the surgeon. Immunohistochemistry and PH of the obtained material were performed.

Results: Ga-68 DOTA-TOC PET/CT detected primary tumor in ileocecal region with bilobar liver and right iliac bone metastases (osteoblastic lesion on F-18 fluoride PET/CT). Compared to previous findings it was partial remission. MR registered regression of predescribed liver metastases. Kidney scintigraphies, GFR and TER were normal. Chromogranin A=836μg/l (normal<100) serotonin=852μg/l (normal:40-200). Patient tolerated well the third cycle of PRRNT, which showed intensive binding to somatostatin receptors. Intraoperative gamma probe localized the primary tumor, liver metastases, but also bilateral ovarian metastases not visualized at Ga-68 DOTA-TOC PET/CT imaging. Bilateral adnexectomy was performed (with right hemicolectomy, excision of hepatic S3 and peritoneum-partly). Histopathology confirmed subperitoneal metastases in both ovaries.

Conclusion: Intraoperative somatostatin receptor detection of primary NET and meatastases after Lu-177 PRRNT is feasible and more sensitive than Ga-68 DOTA-TOC PET/CT. It might aid surgeon for more complete tumor resection and in localization of small lesions (<5mm).

P-041

Title of Presentation: A Case of Two Well-differentiated Not Related Neuroendocrine Tumors Detected by 68 Gallium-SSTR-PET/CT

Karl Khatib, Kaemmerer Daniel


Department of Digestive Surgery Bad Berka, Eberhard Hasche Weg 7. 99437 Bad Berka, Germany

Introduction: There is few information concerning the follow-up of the typical carcinoids of the lung (TCL) and more generally of the neuroendocrine tumors (NET) after surgery. The purpose of this case report is to show that TCL patients are at risk to develop metastases as well as primar NETs of other organs, especially from the gastro-intestinal tract. We will present the case concerning a patient, who developed, 4 years after a resected TCL, an ileum-NET with a single peripancreatic lymphonodular metastasis, and how this new occurence has been efficiently detected by a 68 Ga-SSTR-PET/CT and surgically removed by using Gamma probe detection. Furthermore we want to introduce some suggestions for the follow up of such patients underlining the importance of the somatostatin receptor PET/CT.

The typical carcinoid tumors of the lung (TCL) are rare and sometimes considered as local disease. They are growing slowly (low Ki-67 <2%) and have a good prognosis (88%, 5 years survival) [1] . Surgery is the treatment of choice and could be performed mostly with curative intent. TCLs represent a very little subgroup of brochopulmonary neuroendocrine tumors which contain atypical carcinoid tumors, large cell neuroendocrine carcinomas and small-cell lung carcinomas. The TCLs share histological characteristics, resembling NETs found elsewhere in the body, however they seem having a reduced tendancy to disseminate, and can be differentiated from NETs of other origins true their immunohistochemical pattern [2, 4, 5] . Even if the malignancy potential is low, the patients having a TCL are at risk for rare tumor recurrence and metastatic disease. [9] Currently, there are no specific guidelines for the follow-up of typical lung carcinoids. Based on the poor capacity to disseminate, the follow-up of these patients is often subject to negligence. If any follow-up has been done, it mostly consists in bronchoscopy and computed tomography. In the overwhelming majority the laboratory investigations (chromogranin A) and molecular imaging studies, using somatostatin analogs, are missing, whereas topical recommendations are already existing in some single studies!

Case Report: January 2007, an 68 years old woman was admitted in the thoracic surgery for a bisegmental left lungresection. This resection was decided after a hasardous discovery of a 1,4 cm nodule in the lingula. This nodule was showing criterions of malignancy in the computed tomography of the thorax. The bronchoscopic findings were normal. Preceeding surgery an F-18 FDG-PET was performed as recommended in staging of pulmonary tumors. Itshowed a discreetly augmented glucose uptake from this nodule without associated suspicious mediastinal lymphadenopathies. The resection of the lingula and the mediastinal lymphadenectomy was done on January 2007. The anatomopathological expertise concluded on a 12 mm typical carcinoid (Ki-67 less than 5%) with positive expression of chromogranin A, synaptophysin and TTF1. [2] None of he lymhnodes was invaded, the final staging was pT1 pN0 cM0. Afterwards the follow-up was planed trimestrially. [8] End of 2010 as the tumormarkers were rising up (CgA, specially serotonin) and the patient complained about recurrent abdominal pain, a 68 Gallium-DOTATOC PET-CT was realised and stated the presence of a tumor in the terminal ileum associated with a single parapancreatic lymphadenopathy. [3] The rest of staging showed no suspicious metastases. February 2011, a radical right hemicolectomy and an extended lymphadenectomy was performed, using a Gallium-68-labeled gamma probe. The gamma probe enabled to locate this peripancreatic single lymphnode metastasis in real time. The histological statement brought a well differentiated NET from the ileocoecal valve with a single lymphnode metastasis. The final UICC staging was pT2, pN1, pM0, L0, V0, R0. The immunohistological marker screening was positive for chromogranin A, synaptophysin, SST2A and CDX-2, negative for TTF1. This immunohistochemical pattern was proving the intestinal appartenance of this second tumor and exclude any correspondance with the first pulmonary NET. [4,5] 14 days after surgery the patient left the hospital.

Discussion: This case report is exposing two independant NET from different origins occuring in the same patient in a 4 years delay. The first one was a typical carcinoid of the lung and the second one, a neuroendocrine tumor of the ileum which has been detected by a 68 Gallium-somatostatin receptor PET-CT ( 68 Gallium-SSTR-PET/CT) made in the follow-up. The possible interdependance of this tumors has been ruled out true the immunohistochemical patterns of each one. The metastatic extension of the gastrointestinal NET obtained after surgical and anatomo-pathological examination was fully concording with preoperative findings given by the 68 Gallium-PET-CT. Such accurate results have been also reported by Frilling et al. [3] However it is still known that the 68 Ga-SSTR-PET/CT has a lower sensitivity in small primaries and metastasis. In such cases it has been reported by Kaemmerer et al. [10] that an intraoperative use of a 68 Gallium-labelled gamma probe could improve the detectability of small lesions. Prooving a largest extension of the lymphatic infiltration than as expected prior to surgery true the 68 Ga-SSTR-PET/CT staging, the intraoperative use of a gamma probe often results in the extension of the planed lymphadenectomy. Identification of previously occult metastases and localization of hidden lymphatic lesions are principle reasons for using the gamma probe detection. [10] Despite the fact that there is no literature about the risk of occurence of a second independant NET by non-MEN-patients, we think that a 68 Ga-SSTR-PET/CT has to be planned and should take part of the regularly follow-up of every TCL patient, whether the tumor markers are augmented or not. [8] In our case an somatostatin-receptor-imaging should have been performed after the histopathological finding resulted in the diagnosis of a NET. With regard to the low KI-67 it can be assumed that the ileum-NET could have been detected much earlier. A simultaneous appearance of both different tumor entities cannot be excluded. The 68 Ga-SSTR-PET/CT has an excellent sensibility (95%) and sensitivity. [6,7] It permits an accurate preoperative staging, a postoperative comparative study from the resection results, and can be very usefull in the follow-up, detecting metastases or a new recurrence. The frequency of this technical sophisticated and molecular imaging procedure has still to be determined.

References

1. Gustafsson BI, Kidd M, Chan A, Malfertheiner MV, Modlin IM. Bronchopulmonary neuroendocrine tumors. Cancer. 2008 Jul 1;113(1):5-21. Review.

2. Du EZ, Goldstraw P, Zacharias J, Tiffet O, Craig PJ, Nicholson AG, Weidner N, Yi ES. TTF Expression is specific for Lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location. Hum Pathol. 2004 Jul;35(7):825-31

3. The impact of 68 Ga-DOTATOC positron emission tomography/ computed tomography on the multimodal management of patients with neuroendocrine tumors. Frilling A, Sotiropoulos GC, Radtke A, Malago M, Bockisch A, Kuehl H, Li J, Broelsch CE. Ann Surg. 2010 Nov;252(5):850-6

4. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neo-plasms of unknown origin. Lin X, Saad RS, Luckasevic TM, Silverman JF, Liu Y. Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):407-14

5. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Srivastava A, Hornick JL. Am J Surg Pathol. 2009 Apr;33(4):626-32

6. Gallium-68 PET: a new frontier in receptor cancer imaging, Al-Nahhas A, Win Z, Szyszko T, Singh A, Nanni C, Fanti S, Rubello D. Anticancer Res. 2007 Nov-Dec;27(6B):4087-94

7. Role of ( 68 )Ga-DOTATOC PET/CT in the evaluation of primary pulmonary carcinoids. Jindal T, Kumar A, Venkitaraman B, Dutta R, Kumar R. Korean J Intern Med. 2010 Dec;25(4):386-91. Epub 2010 Nov 27

8. Tumor markers in neuroendocrine tumors. Eriksson B, Oberg K, Stridsberg M. Digestion. 2000;62 Suppl 1:33-8

9. Long-term outcomes and prognostic factors of patients with surgically treated pulmonary carcinoid: our institutional experience with 104 patients. Aydin E, Yazici U, Gulgosteren M, Agackiran Y, Kaya S, Gulhan E, Tastepe I, Karaoglanoglu N. Eur J Cardiothorac Surg. 2011 Apr;39(4):549-54.

10. Kaemmerer et al. NET-Surgery using Gamma Probe 2011 Clin Nucl Med [In press]

P-042

One Day Protocol: Dual Tracer/Dual Isotope FDG-18 and Ga-68 DOTA-NOC PET/CT Study of a Child with Neuroblastoma to Determine the Metabolic Tumor Status

Juan P. Oliva, Richard P. Baum 1


Nuclear Medicine Clinic, National Institute of Oncology, Havana, Cuba, 1 Department Nuclear Medicine/PET Center, Central clinic Bad Berka, Germany

We report on a 6 year-old boy with a history o neuroblastoma. The tumor was first diagnosed in March 2004, arising from the right adrenal gland as confirmed by fine needle aspiration biopsy, Ultrasound, CT scan as well as tumor markers. Due to the size and extension, the tumor was inoperable at his time and two cycles of chemotherapy (vincristin, cisplatin, etopoxid, and cyclophosphamide alternating with vincristin, carboplatin, etopoxid and cyclophosphamide) were given. Then, the patient underwent retroperitoneal surgery and the right adrenal gland and the tumor were completely resected. After the operation, the patient received 4 additional cycles of chemotherapy until March 2005. During August and September 2005 the patient complained about abdominal pain and recurrence was suspected. Ultrasound and CT scan were repeatedly performed, but were unclear. In December 2005, an I-131 MIBG scan(148MBq, 4mCi iv, planar images and SPECT from 24 hrs until 6 d p i) revealed only a normal left adrenal gland but no recurrence, proving that the tumor had no MIBG uptake. In January 2006 the child (121 cm height, weight 21 kg) was submitted to the PET/CT Center of the Central clinic Bad Berka, Germany for receptor PET/CT using 68-Ga/DOTA-NOC, a high affinity pansomatostatin analogue. NSE was determined in serum prior to the PET/CT study and was elevated (24.8 ng/ml, cutoff 15) The patient received 46 MBq (1.24 mCi) Ga-68 DOTA-NOC i.v. and a whole-body PET/CT was performed 75 min p.i. There was no abnormal uptake proving that the recurrence had no somatostatin receptors. After this negative result it was decided to perform additionally a F-18 FDG PET/CT study(with contrast enhanced low dose CT scan). After a fasting time of 6 hours, the patient received 151 MBq (4.1 mCi)F-18 FDG. Whole-body PET/CT was performed 75 min.p.i and a recurrence was clearly depicted as hypermetabolic tumor(SUV max . 8.1, molecular tumor volume(MTV) 15,2 cm 3 , 27×27×40mm in diameter, craniocaudal extension 4,5 cm) between the vena cava inferior and the aorta with extension to the psoas muscle and infiltration of the right renal artery. Additionally, a weak hypermetabolic focus was detected in the right spinailiaca anterior superior(SUV 2.0). The results of the F-18 FDG study were confirmed by surgery performed 1 week later. To our best knowledge, this is the first report on a one day protocol applying two different PET tracers labeled with two different radionuclides in a neuroblastoma patient. This study confirms previous reports stating that some neuroblastoma recurrences may have undifferentiated cells that do not express somatostatin receptors, but show high glucose consumption which has also significant(adverse) impact on prognosis.

References

1. Ruffini V, Calcagni ML, Baum RP. Imaging of neuroendocrinicine tumors. Semin Nucl Med 2006; 36:228-47

2. Chueung, NV. Neuroblastoma. Pediatric Oncology. Springer, Berlin, Heidelberg, 2005

 
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