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   Table of Contents - Current issue
Coverpage
July-September 2018
Volume 17 | Issue 3
Page Nos. 131-210

Online since Thursday, June 21, 2018

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EDITORIAL  

Red flag or red herring Highly accessed article p. 131
John Richard Buscombe
DOI:10.4103/wjnm.WJNM_25_18  
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REVIEW ARTICLE Top

188Re-HEDP therapy in the therapy of painful bone metastases Highly accessed article p. 133
Knut Liepe
DOI:10.4103/wjnm.WJNM_85_17  
For bone-targeted radionuclide therapy (BTRT), different commercial radiopharmaceuticals are available such as strontium-89, 186Rhenium-hydroxyethylidene diphosphonate (186Re-HEDP), Samarium-153-ethylenediamine tetramethylene phosphonic acid, and radium-223. Unfortunately, the commercial available radiopharmaceuticals are very expensive (from 1,200 to 36,000€ per patient in Europe). The 188W/188Re generator is an ideal source for the long-term (4–6 months) continuous availability of 188Re suitable for the preparation of radiopharmaceuticals for different radionuclide therapies. Labeling at HEDP, it can use cost-effective for BTRT, if enough patients are available for therapy. And so, 188Re-HEDP is the ideal candidate in developing countries which high population to replace the other agents. Two German groups documented a response rate of 80% without any severe side effects and similar bone marrow toxicity compared to the other compounds for 188Re-HEDP. Using 188Re-HEDP in repeated treatments, a prolonged overall survival of repeated to single application was observed (from 4.5 months for single to 15.7 months using ≥≥3 applications).
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ORIGINAL ARTICLES Top

Positron emission tomography-computed tomography for inguinal nodes in vulvar cancer p. 139
Jorge Daniel Oldan, Stephanie A Sullivan
DOI:10.4103/wjnm.WJNM_32_17  
We aimed to determine the sensitivity and specificity of fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) for the spread of disease to inguinal lymph nodes in vulvar cancer. A retrospective review of vulvar cancer patients who underwent both inguinal nodal sampling and dissection as well as FDG PET-CT was performed, with 21 patients meeting criteria. The sensitivity and specificity of the FDG PET-CT imaging was performed using a combination of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Using an SUVmaxcutoff of 4.5 or of two times the average liver uptake, we had a 100% sensitivity and 89% specificity for positive inguinal nodes. MTV and TLG did not add to sensitivity or specificity. We conclude that FDG PET-CT has good sensitivity for inguinal nodal spread in vulvar cancer, and either a quantitative or semiquantitative approach is effective.
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Multipurpose computed tomography window for fusion display with functional imaging p. 145
Nghi C Nguyen, Kaveh Vejdani
DOI:10.4103/wjnm.WJNM_34_17  
Current positron emission tomography/computed tomography (PET/CT) and single photon emission CT (SPECT)/CT displays have major drawbacks, in that the CT only shows one tissue type at a time, which leads to a suboptimal fusion display. We developed a multipurpose CT level/window aiming at enhancing fusion display. A total of thirty CT examinations as part of fluorodeoxyglucose PET/CT examinations (15 were open source from the OsiriX website and 15 from our PET facility) and the open-source software MIPAV were used. During the development phase, a nuclear medicine physician manually modified the lookup table in a way that preserved the soft tissue contrast as well as enhanced the lung and bone tissue as much as possible. The developed multipurpose CT window was used in the subsequent validation phase and scored by two nuclear medicine physicians, who scored the image quality based on a 3-point score. Descriptive statistics was used to summarize the visual scores. The multipurpose CT window is a composite of several segments of linear CT levels/windows and contains an inverted linear level/window in the low range of Hounsfield unit designed to enhance lung/soft tissue contrast. In doing so, the multipurpose CT window preserves the high soft tissue contrast; the visualization of the lung parenchyma is satisfactory; the contrast for the bone tissue is improved but remains suboptimal when compared with conventional bone window. The multipurpose CT window was found to be “very useful” (median score 3; 95% confidence interval [CI] 2.0–3.0) for the purpose of fusion with functional imaging, with a prevalence asymmetry index 0.97 (95% CI 0.83–1.0). The multipurpose CT window was developed for image fusion and is not intended for diagnostic purposes. It shows favorable similarities to conventional CT windows with only minor artifacts and allows for enhanced visualization of fused PET/CT and SPECT/CT images. The multipurpose CT window is particularly valuable for case review/demonstrations on standard personal computers and handheld devices (smartphones, tablets).
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99mTc-Hynic-TOC imaging in the diagnostic of neuroendocrine tumors p. 151
Knut Liepe, Andreas Becker
DOI:10.4103/wjnm.WJNM_41_17  
The aim of this study was to assess the potential of 99mTc-Hynic-TOC imaging in the primary diagnosis and follow-up of midgut neuroendocrine tumors (NETs). In comparison to 111In-octreotide, 99mTc-Hynic-TOC has a higher imaging quality and leads to a lower radiation absorption in patients. 99mTc-Hynic-TOC was used for assessing primary diagnosis (n = 14) and during follow-up (n = 17) in patients with NETs. The scintigraphic findings were compared with computed tomography scans and follow-up. In 31 patients, 34 somatostatin receptor scans using 99mTc-Hynic-TOC were performed. The primary diagnoses were midgut NET. The scintigraphy was true positive in 17 patients, true negative in 9, false negative in 4, and false positive in 1. From these data, a sensitivity of 81%, specificity of 90%, positive predictive value of 94%, and negative predictive value of 69% were calculated. In summary, 99mTc-TOC represents a useful radiotracer in imaging SSTR-expressing tumor lesions with slightly higher sensitivity, higher imaging quality, and lower radiation exposure for patients compared to 111In-octreotide. A 1-day double-acquisition protocol should be used to reduce false-positive findings of the gut.
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The use of Deauville 5-point score could reduce the risk of false-positive fluorodeoxyglucose-positron emission tomography in the posttherapy evaluation of patients with primary bone lymphomas p. 157
Luigi Rigacci, Sofia Kovalchuk, Valentina Berti, Benedetta Puccini, Lara Mannelli, Gemma Benelli, Catia Dini, Alberto Pupi, Alberto Bosi
DOI:10.4103/wjnm.WJNM_42_17  
Primary bone lymphoma (PBL) is a rare disease. Little is reported about response evaluation procedures in these patients. Our aim was to evaluate response to therapy according to fluorodeoxyglucose-positron emission tomography (FDG-PET) results, and in particular to test the Deauville 5-point scale as compared to the visual evaluation of FDG-PET scans in PBL. In this single-center study, we diagnosed 31 consecutive patients with PBL, of which 24 were evaluated with end-of-treatment FDG-PET. Patients' ages ranged from 19 to 82 years. Six patients were treated with chemotherapy, 24 with chemotherapy and radiotherapy, and one patient with radiotherapy alone. Six patients were affected by a pathological fracture. Four patients died within the range of 3 to 36 months after diagnosis. The average follow-up of the remaining patients was 70 (24–173) months. Overall survival was 87% at 5 years. The only positive prognostic factor was complete remission after chemotherapy. According to visual criteria, end-of-treatment FDG-PET was evaluated in 24 patients and it was positive in 11 (46%) and negative in 13 patients. We organized a retrospective central-blinded revision of end-of-therapy FDG-PET scans using the 5-point Deauville Score (DS). We reviewed 17 out of 24 patients and obtained the following results: at the end of therapy, 12 patients with DS score 2, three patients with DS score 3, one patient with DS score 4, and none with DS score 5. Considering that all the 24 patients achieved complete remission after treatment, visual interpretation produced 11/24 false-positive results, and DS interpretation produced 1/17 false-positive results, thus significantly reducing the number of false positives. In PBL, the final evaluation at the end of therapy with FDG-PET should be evaluated using Deauville 5-point scale in order to significantly reduce the risk of false-positive scans.
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Higher event rate in patients with high-risk Duke Treadmill Score despite normal exercise-gated myocardial perfusion imaging p. 166
Maseeh uz Zaman, Nosheen Fatima, Areeba Zaman, Unaiza Zaman, Rabia Tahseen, Sidra Zaman
DOI:10.4103/wjnm.WJNM_43_17  
This prospective study was carried out to find the negative predictive value of various Duke Treadmill Scores (DTSs) in patients with normal myocardial perfusion imaging (MPI). This study was conducted from August 2012 to July 2015, and 603 patients having normal exercise MPIs were included. Patients were followed for 2 years for fatal myocardial infarction (FMI) and nonfatal myocardial infarction (NFMI). Follow-up was not available in 23 patients, leaving a cohort of 583 participants. DTS was low risk (≥5) in 286, intermediate risk (between 4 and − 10) in 211, and high risk (≤−11) in 86 patients. Patients with high- and intermediate-risk DTS were significantly elder than low-risk DTS cohort. Patients with high-risk DTS had significantly higher body mass index with male preponderance compared to other groups. No significant difference was found among three groups regarding modifiable or nonmodifiable risk factors and left ventricular ejection fraction. On follow-up, single FMI was observed in high-risk DTS group (log-rank test value = 5.779, P = 0.056). Five NFMI events were observed in high-risk DTS (94.2% survival; log-rank test value = 19.398, P = 0.0001; significant) as compared to two events each in low- and intermediate-risk DTS (nonsignificant). We conclude that patients with normal exercise MPI and low-to-intermediate risk DTS have significantly low NFMI. High-risk DTS despite normal exercise MPI had high NFMI. Further, validation studies to find the predictive value of symptomatic and asymptomatic ST deviation resulting in high-risk DTS in patients with normal exercise MPI are warranted.
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Use of 18F FDG PET and the short temporal response of Hodgkin's disease to RIT p. 171
Ewa Nowosinska, Pei San Chan, John R Buscombe
DOI:10.4103/wjnm.WJNM_50_17  
Radioimmunotherapy (RIT) has been available for some time to treat patients with non-Hodgkin's lymphoma, but its use in Hodgkin's lymphoma has been less available, partly because of the need to find an appropriate antibody. A new radioiodinated chimeric antibody directed against the CD25 epitope (131I basiliximab) seems promising, but assessment of response has been difficult. 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) has become a standard method by which the response of Hodgkin's disease to chemotherapy is both predicted and assessed with well-understood criteria of response. The aim of this study is to determine18F-FDG-PET can be used to assess response to RIT. Pre- and post-treatment 18F-FDG-PET imaging was performed in a series of 13 patients with advanced Hodgkin's disease who had failed conventional therapy and had been enrolled on a compassionate use program for treatment with 131I basiliximab. The 131I basiliximab was given at an activity of 1200MBq/m2 with one patient receiving 2 cycles and the rest a single cycle. The 18F-FDG-PET studies were compared using the “Deauville” criteria and by comparing the maximum standardized uptake value (SUVmax) of target tumors before and 4 and 8 weeks after treatment. All patients survived long enough for their initial 18F-FDG-PET-computed tomography scan at 4 weeks after their 131I basiliximab therapy. One out of ten patients with “Deauville” Grade 4 or 5 response died during the 6-month follow-up period. Two out of three patients with a “Deauville” Grade 2 or 3 response died in the follow-up period. The mean SUVmax pretreatment was 11.9 (±4.7); at 4-week posttreatment, the mean SUVmax was significantly lower at 6.5 (±5.8) (P = 0.02). At 8 weeks, the mean SUVmax was 8.8 (±7.0), which was not significantly different from the pretreatment level. 18F-FDG-PET imaging is able to predict the short-term response to treatment of Hodgkin's disease by RIT, and an initial poor response appears to predict poor outcome. Early changes in 18F-FDG-PET uptake did not predict sustained response and by 8 weeks all but one patient had recurrent disease.
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The association of human immunodeficiency virus and skeletal metastases in breast cancer using Tc-99m methyl diphosphonate bone scan Highly accessed article p. 178
Masha Maharaj, Nisaar Korowlay
DOI:10.4103/wjnm.WJNM_58_17  
Skeletal involvement occurs in 30%–70% of all cancer patients, with breast cancer (BC) being the leading cause for bone metastases in women and prostate cancer in men followed by lung cancer. Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome. It is yet unknown what is the impact of HIV to the onset and progression of bone disease in BC. The purpose of the study was to determine the association of HIV infection and skeletal metastases in BC using skeletal scintigraphy. A retrospective analysis of 25 female BC patients' bone scans was performed. The 25 bone scans of 12 patients known HIV positive and 13 patients who were known HIV negative, of similar age and histology, were compared. All 13 HIV negative patients had a positive bone scan. Of the 12 HIV-positive patients, 4 patients on highly active antiretroviral therapy (HAART) had positive bone scans for skeletal metastases. The remaining eight HIV-positive patients had negative bone scans, of which six were on HAART and two were not on HAART. In our study, HIV infection was not found to be a contributing risk factor for skeletal metastases. From our small series, it appears that HIV patients and on HAART have a delay in the onset of skeletal metastases in BC.
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The minimum amount of fluids needed to achieve the fastest time to reach permissible level for release in well-differentiated thyroid patients undergoing high-dose I-131 therapy p. 182
Alex Khoo Cheen Hoe, Lee Yeong Fong, Fatin Nadhirah Abdul Halim, Quek Kia Fatt, Fadzilah Hamzah
DOI:10.4103/wjnm.WJNM_59_17  
Radioiodine (131I) therapy is the mainstay of treatment for patients who had undergone total thyroidectomy for well differentiated thyroid carcinoma. Increased fluid intake has always been encouraged to minimize the risk of non-target organ exposure to I-131radiation. This study aimed to determine the minimum amount of fluids needed for patients to have the fastest time to achieve permissible level for release after high dose I-131therapy. Methodology: All the patients who were treated with high dose I-131from 18th January 2016 till 31st December 2016 in Hospital Pulau Pinang, Malaysia were recruited. The data from 126 patients on thyroxine hormone withdrawal (THW) group and 18 patients on recombinant human thyroid stimulating hormone (rhTSH) group were analysed. There is no change in patient management in terms of preparation, dose or post therapy whole-body scan. Fluid intake of patients were monitored strictly and whole-body retention of I-131are measured using ionizing chamber meter immediately after ingestion of I-131then at 1 hour, 24 hours, 48 hours, 72 hours and 96 hours. Results: The median time to achieve permissible release limit (50 μSV/hr at 1 meter) was 21.6 hours and 22.1 hours post-ingestion of I-131in the THW and rhTSH group respectively. The minimum amount of fluid needed to reach permissible release limit in the fastest time was 2,103 ml and 2,148ml for the THW and TSH respectively. Conclusion: Clinicians would be able to evidently advise their patient on the amount of fluid to consume and utilize their isolation wards faster to treat more patients.
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Visual detection of regional brain hypometabolism in cognitively impaired patients is independent of positron emission tomography-magnetic resonance attenuation correction method p. 188
Ana M Franceschi, Valentino Abballe, Roy A Raad, Aaron Nelson, Kimberly Jackson, James Babb, Thomas Vahle, Matthias Fenchel, Yiqiang Zhan, Gerardo Hermosillo Valadez, Timothy M Shepherd, Kent P Friedman
DOI:10.4103/wjnm.WJNM_61_17  
Fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/MR) is useful for the evaluation of cognitively-impaired patients. This study aims to assess two different attenuation correction (AC) methods (Dixon-MR and atlas-based) versus index-standard computed tomography (CT) AC for the visual interpretation of regional hypometabolism in patients with cognitive impairment. Two board-certified nuclear medicine physicians blindly scored brain region FDG hypometabolism as normal versus hypometabolic using two-dimensional (2D) and 3D FDG PET/MR images generated by MIM software. Regions were quantitatively assessed as normal versus mildly, moderately, or severely hypometabolic. Hypometabolism scores obtained using the different methods of AC were compared, and interreader, as well as intra-reader agreement, was assessed. Regional hypometabolism versus normal metabolism was correctly classified in 16 patients on atlas-based and Dixon-based AC map PET reconstructions (vs. CT reference AC) for 94% (90%–96% confidence interval [CI]) and 93% (89%–96% CI) of scored regions, respectively. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% (P = 0.669) and 90%/91% (P = 0.937) for atlas-based and Dixon-based AC maps. Interreader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% (Κ =0.82) and 93% (Κ =0.84) of regions, respectively. Intrareader agreement for detection of regional hypometabolism was high, with concordant outcome assessments when using atlas- and Dixon-corrected data in 93%/92% (Κ =0.79) and 92/93% (Κ =0.78). Despite the quantitative advantages of atlas-based AC in brain PET/MR, routine clinical Dixon AC yields comparable visual ratings of regional hypometabolism in the evaluation of cognitively impaired patients undergoing brain PET/MR and is similar in performance to CT-based AC. Therefore, Dixon AC is acceptable for the routine clinical evaluation of dementia syndromes.
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CASE REPORTS Top

Metastatic clear cell renal cell carcinoma demonstrating intense uptake on 68Ga-DOTATATE positron emission tomography: Three case reports and a review of the literature p. 195
David P Nadebaum, Sze Ting Lee, Mehrdad Nikfarjam, Andrew M Scott
DOI:10.4103/wjnm.WJNM_38_17  
68Ga-DOTATATE positron emission tomography (PET) is a molecular imaging technology which has shown superiority over 111In-octreotide scanning for the detection and staging of neuroendocrine tumors. We report three patients with pancreatic masses that were ultimately diagnosed as clear cell renal cell carcinoma (ccRCC) metastases on histopathology. During their initial diagnostic assessment, the three patients underwent both 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATATE PET. While all three patients' lesions showed variable 18F-FDG avidity, uptake on 68Ga-DOTATATE PET was comparatively intense. The small case series illustrates the need to consider ccRCC in the differential diagnosis of 68Ga-DOTATATE avid lesions.
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Massive pericardial effusion: A rare and easily missed finding in myocardial perfusion scintigraphy p. 198
Kwan Kit Wu, Boom Ting Kung, Ting Kun Au Yong
DOI:10.4103/wjnm.WJNM_39_17  
A 72-year-old gentleman underwent myocardial perfusion scintigraphy (MPS) for sinus tachycardia of unknown cause. Baseline electrocardiography (ECG) showed sinus tachycardia and electrical alternans. Thallium-201 stress-redistribution MPS was performed with dipyridamole stress. On the raw projection images, a photopenic “halo” was noted surrounding the heart. Reconstructed slices showed small left ventricle with no obvious perfusion defect. Review of single-photon emission computed tomography/computed tomography images showed suspected large pericardial effusion. The patient was admitted and Echocardiography showed significant circumferential pericardial effusion with early tamponade effect. Subsequent bedside pericardiocentesis aspirated 800 ml blood-stained fluid and the cytology yielded metastatic adenocarcinoma with features suggestive of pulmonary primary. Pericardial effusion is a rare finding in MPS. Finding of a “halo” around the heart should raise suspicion on the presence of pericardial effusion and confirmatory investigation such as ECG may be warranted.
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Gallbladder activity on sodium fluoride positron emission tomography/computed tomography bone scan p. 201
Ismet Sarikaya, Abdelhamid H Elgazzar, Mahmoud A Alfeeli, Ali Sarikaya
DOI:10.4103/wjnm.WJNM_45_17  
We incidentally identified gallbladder activity on 18F sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) bone images in five patients. Variable degree of bowel activity is usually seen on NaF PET/CT images, and its mechanism is unknown. Gallbladder activity in our cases may indicate that hepatobiliary excretion of the 18F NaF is the reason for bowel activity on NaF PET/CT images. However, excretion of radiotracer through bowel may also contribute to the bowel activity.
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Use of radioguided surgery in abdominal wall endometriosis: An innovative approach p. 204
Geraldo Sérgio Farinazzo Vitral, Hakayna Calegaro Salgado, João Matheus de Castro Rangel
DOI:10.4103/wjnm.WJNM_47_17  
Endometriosis is characterized by the presence of endometrial glands and stroma outside the uterine cavity. The occurrence of endometriosis in the anterior abdominal wall is often associated with previous cesarean section, once the spread of endometrial cells during the surgical procedure is a biologically fact possible. A 43-year-old patient, with cesarean section history and pelvic endometriosis diagnosed for over 10 years, presented with progressive abdominal pain. Tests showed cystic image with 1.6 cm of diameter and debris, located in mid-lower portion of the rectus abdominis left, suggesting abdominal wall endometriosis. This abdominal wall lesion was not identifiable in the clinical examination (impalpable), which is why we opted for the use of preoperative marking technique with radioisotope called Radioguided Occult Lesion Localization (ROLL). The use of ROLL in this case allowed rapid surgical identification of endometriotic lesion and its complete excision.
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Fluorodeoxyglucose, sodium fluoride, and prostate-specific membrane antigen positron emission tomography studies for treatment response assessment in prostate cancer p. 207
Ismet Sarikaya, Abdelhamid Elgazzar, Ali Sarikaya, Mahmoud Alfeeli
DOI:10.4103/wjnm.WJNM_51_17  
Various positron emission tomography (PET) studies are available for prostate cancer which show various successes at demonstrating primary, recurrent, or metastatic tumor and assessing response to treatment. In this case report, we will present and compare pre- and post-therapy fluorodeoxyglucose, sodium fluoride, and gallium-68 prostate-specific membrane antigen PET images of a patient with prostate cancer.
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