Clinical Nuclear Medicine

Thyroid Cancer Bone Metastasis: Survival and Genomic Characteristics of a Large Tertiary Care Cohort Purpose Bone metastasis (BM) in differentiated thyroid cancer (DTC) is the second most common site of metastasis after lung. Bone metastases are associated with worse prognosis in DTC. In this study, we examined risk factors for overall survival in patients with BM and for the first time explore the pattern of genomic alterations in DTC BM. Patients and Methods A Health Insurance Portability and Accountability Act (HIPAA) compliant, institutional review board–approved retrospective evaluation of the medical record was performed for all patients treated at a single institution for thyroid cancer over a 16-year period. Seventy-four patients met inclusion criteria. Multiple prognostic factors including age, sex, genes, radioactive iodine, and radiation or kinase inhibitor therapies were analyzed. Univariate and multivariate analyses were performed. Results Treatment with external beam radiation was found to significantly increase survival (P = 0.03). The 5-year survival rate was 59% and median survival was 92 months. Patients who developed bone metastasis earlier tend to live longer (P = 0.06). The presence of TERT and BRAF mutations did not significantly worsen the prognosis (P = 0.10). Conclusion Patients with DTC can benefit from early treatment with external beam radiation therapy, especially those who develop bone metastasis within 3 years of primary TC diagnosis. Kinase inhibitor treatment tended to prolong survival but not in a statistically significant manner. Sex, age, and TERT or BRAF genetic mutations did not significantly affect the prognosis. Received for publication October 26, 2018; revision accepted March 30, 2019. Conflicts of interest and sources of funding: This study was supported by R01 CA201250-01A1 “124I-NaI PET: Building block for precision medicine in metastatic thyroid cancer” Grant (JRO, RKG, SML) as well as by the Center for Targeted Radioimmunotherapy and Diagnosis and the Ludwig Center for Cancer Immunotherapy. This research was also funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. None declared to all authors. Correspondence to: Joseph R. Osborne, MD, PhD, Chief of Nuclear Medicine Department of Radiology New York—Presbyterian Weill Cornell Medical Center 520 E 70th Street, Starr-2, New York, NY 10021. E-mail: jro7001@med.cornell.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Comparison of 11C-Choline and 11C-Methionine PET/CT in Multiple Myeloma Purpose PET/CT with both 11C-choline and 11C-methionine has recently been reported to offer advantages over 18F-FDG for imaging in multiple myeloma (MM). The aim of this study was to directly compare the diagnostic performance of both non-FDG radiotracers in MM patients. Methods Nineteen patients with a history of MM (n = 18) or solitary bone plasmacytoma (n = 1) underwent both 11C-choline and 11C-methionine PET/CT for diagnostic imaging. In this retrospective analysis, scans were compared on a patient and on a lesion basis. In 12 patients, respective tracer uptake in the iliac crest was correlated with the extent of malignant bone marrow plasma cell infiltration. Results 11C-methionine detected more intramedullary MM lesions in 8 (42.1%) of 19 patients. In the remainder (11/19 [57.9%]), both 11C-choline and 11C-methionine provided equal results. 11C-methionine demonstrated higher lesion-to-muscle ratios (P = 0.0001). In the 12 patients in whom a recent bone marrow biopsy was available, SUVmean as well as SUVmax correlated significantly with the degree of malignant plasma cell infiltration for both 11C-methionine (SUVmean: r = 0.85, P < 0.001; SUVmax: r = 0.82, P = 0.001) and 11C-choline (SUVmean: r = 0.72, P < 0.008; SUVmax: r = 0.73; P = 0.006). Conclusions Our data suggest that 11C-methionine PET/CT might be more sensitive than 11C-choline PET/CT for the detection of active MM lesions. Received for publication January 23, 2019; revision accepted April 11, 2019. C.L. and M.K. contributed equally to this work. Author Contributions: Conception and design: C.L., M.K., L.R., H.H. Development of methodology: C.L., M.D.V., M.S., K.M.K., H.H., S.S. Acquisition of data: C.L., M.K., M.D.V., M.S., L.R., K.M.K. Analysis and interpretation of data: C.L., M.K., M.D.V., M.S., L.R., K.M.K., H.H. Writing, review and/or revision of the manuscript: all authors. Administrative, technical, or material support: HE, A.K.B., H.H., S.S. Supervision: H.E., A.K.B., HH, S.S. All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This work was supported by Wilhelm-Sander-Stiftung (grant 2017.061.1). Conflicts of interest and sources of funding: none declared. Correspondence to: Constantin Lapa, MD, Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacher Strasse 6, D-97080 Würzburg, Germany. E-mail: lapa_c@ukw.de. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma Purpose To retrospectively investigate the uptake of 18F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG). Methods Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth. Results All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1–20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1–84.4). In 4 patients, 18F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR. Conclusions The uptake of 18F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of 18F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis. Received for publication September 7, 2018; revision accepted April 11, 2019. Conflicts of interest and sources of funding: Blue Earth Diagnostics Ltd, marketer of 18F-fluciclovine (Axumin), has supported research funding to Oslo University Hospital, Oslo, Norway, for clinical studies using 18F-fluciclovine PET/CT in prostate cancer performed by the authors T.V.B. and T.B.-G. T.B.-G. has received honorarium from Blue Earth Diagnostics Ltd for giving user training lectures on 18F-fluciclovine in prostate cancer in June and November 2018. No financial support has been received for this retrospective registry study. Concerning this study, there is nothing to disclose for any of the authors. Correspondence to: Trond V. Bogsrud, MD, PhD, University Hospital of North Norway, Sykehusvegen 38, 9019 Tromsø, Norway. E-mail: Trond.Bogsrud@unn.no. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Interlesional Heterogeneity of Metastatic Neuroendocrine Tumors Based on 18F-DOPA PET/CT Purpose Neuroendocrine tumors (NETs) can produce neuroendocrine amines resulting in symptoms. Selecting the most active amine-producing tumor lesions for local treatment might be beneficial for patients with metastatic small intestinal NET. Tumor burden correlates with catecholamine pathway activity. We analyzed interlesional heterogeneity with 18F-DOPA PET scans in patients with small intestinal NET and investigated if lesions with substantially higher 18F-DOPA uptake could be identified. Methods In this retrospective, observational study, the 18F-DOPA uptake was calculated by dividing SUVpeak of the lesion by the SUVmean of the background organ. The magnitude of heterogeneity between lesions within a patient was calculated by dividing the lesion with the highest by the one with the lowest 18F-DOPA uptake. Lesions with a higher 18F-DOPA uptake than the upper inner or outer fence (>1.5 or 3 times the interquartile range above the third quartile) were defined as lesions with mild or extreme high 18F-DOPA uptake, respectively, and presence of these was determined in patients with 10 lesions or more. Results 18F-DOPA was detected over 680 lesions in 38 patients, of which 35 were serotonin producing. 18F-DOPA uptake varied with a median of 8-fold up to 44-fold between lesions within a patient. In 12 of 20 evaluable patients, lesions with mild high 18F-DOPA uptake were found, and in 5, lesions with extreme high 18F-DOPA uptake. Conclusions 18F-DOPA-PET showed considerable heterogeneity in 18F-DOPA uptake between tumor lesions and identified lesions within patients with mild or extreme high 18F-DOPA uptake. Received for publication October 26, 2018; revision accepted April 11, 2019. Aline M. van der Loo–van der Schaaf is now with the Medical Center Zuiderzee, Lelystad, the Netherlands. Conflicts of interest and sources of funding: none declared. Correspondence to: Annemiek M. E. Walenkamp, MD, PhD, Department of Medical Oncology, University of Groningen, University Medical Center Groningen, DA11 PO Box 30.001, 9700 RB Groningen, the Netherlands. E-mail: a.walenkamp@umcg.nl. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Rapid Decomposition of 99mTc-MAA Complex During Lung Perfusion Imaging A 30-year-old woman with a recent episode of dyspnea was presented. The lung perfusion scan using 99mTc-MAA (macro-aggregated albumin) initially revealed an acceptable lung-to-background activity ratio implying a proper radiopharmaceutical preparation and radiolabeling efficiency. Unexpectedly, later during the scan, rapidly increasing concentration of activity was observed in salivary glands, thyroid and stomach. Rapid breakdown of 99mTc-MAA complexes was considered as a likely explanation for the increase in the circulatory level of the free pertechnetate. Received for publication February 7, 2019; revision accepted April 22, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Mohsen Qutbi, Department of Nuclear Medicine, Taleghani Hospital, Yaman St., Velenjak, Tehran 1985711151, Iran. E-mail: mohsen.qutbi@gmail.com, mohsen.qutbi@sbmu.ac.ir. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Midgut NET With Orbital, Myocardial, Testicular, Lymph Nodal and Pulmonary Metastases Presenting With Bilateral Proptosis—Role of 68Ga-DOTANOC PET/CT Neuroendocrine tumors (NET) are rare neoplasms and commonly metastasize to liver, lymph nodes and less frequently to bones and lungs. Metastases to other organs are extremely rare and we report a case of NET clinically presenting with bilateral proptosis secondary to metastases in orbits. 68Ga-DOTANOC PET/CT demonstrated somatostatin receptor overexpressing lesions in bilateral orbits, small intestine, lymph nodes, lungs, heart and testes in the absence of liver metastases. Received for publication March 7, 2019; revision accepted April 13, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Dr Raja Senthil, Department of Nuclear Medicine and PET/CT, VPS Lakeshore Hospital, Maradu, Nettoor (PO), Kochi, Kerala 682040, India. E-mail: senthilrajapgi@yahoo.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Efficacy of 177Lu Peptide Receptor Radionuclide Therapy for the Treatment of Neuroendocrine Tumors: A Meta-analysis Objective The purpose of this study was to assess the efficacy of 177Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. Methods MEDLINE, EMBASE, and Ovid were systematically searched with keywords “lutetium,” “Lu-177,” “PRRT,” “neuroendocrine,” and “prognosis.” Studies evaluating treatment with 177Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models. Results Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%–38.9%), and disease control rate was 74.1% (95% CI, 67.8%–80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%–41.5%), and disease control rate was 81.1% (95% CI, 76.4%–85.4%). Conclusions Induction therapy, typically 4 treatments, with 177Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates. Received for publication March 19, 2019; revision accepted April 11, 2019. Conflicts of interest and sources of funding: T.P.W.M. is a paid consultant with Galapagos LLC and has received speaker fees from Novartis. The authors otherwise have none declared. Correspondence to: Todd P. W. McMullen, MD, PhD, Department of Surgery, University of Alberta Hospital, 8440-112 St NW, 2D4.41 Walter C. Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada T6G 2B7. E-mail: todd.mcmullen@ahs.ca. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Performance of 18F-FDG, 11C-Methionine, and 18F-FET PET for Glioma Grading: A Meta-analysis Purpose Gliomas constitute the most frequent primary brain tumors. Glioblastoma, the most common and malignant glioma in adults, has dismal prognosis with any current therapy. On the other hand, low-grade gliomas, the second most common type of gliomas, are potentially curative with appropriate treatment. Methods We conducted a meta-analysis to assess the performance of PET tracers with the best available evidence, namely, fluorodeoxyglucose (FDG), 11C-methionine (MET), and 18F-fluoroethyltyrosine (FET), in differentiating low- from high-grade gliomas. Results Twenty-three studies with a total of 994 participants were included in this meta-analysis. The pooled sensitivities of both MET PET and FET PET were found to be significantly higher than of FDG PET (94%, 88%, and 63% respectively, P < 0.001). The pooled specificity of FDG PET was found to be significantly greater compared with both MET PET and FET PET (89%, 55%, and 57%, respectively; P = 0.002). Fluorodeoxyglucose PET was superior in terms of higher positive likelihood ratio values compared with both FET PET and MET PET. Conclusions This meta-analysis indicated that both MET and FET were superior to FDG in terms of sensitivity for identifying glioma grade. Received for publication April 3, 2019; revision accepted April 23, 2019. Conflicts of interest and sources of funding: none declared. This article does not contain any studies with human participants or animals performed by any of the authors. Correspondence to: George A. Alexiou, MD, PhD, Department of Neurosurgery, University of Ioannina School of Medicine, Ioannina 45500, Greece. E-mail: alexiougr@gmail.com; alexiougrg@yahoo.gr. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Quality and Safety in Healthcare, Part LIV: The Need for Organizational Interventions to Prevent Burnout Physician burnout can be a contributing factor to depression, substance abuse, problems with relationships, and thoughts of suicide. Burnout of physicians also results in decreased quality, safety, and outcomes for patients and more financial costs for health-care institutions. It is not enough for health-care systems to focus on helping the individual; these organizations also need to understand that they are the main cause of physician burnout and take appropriate action to reform their processes. Received for publication April 21, 2019; revision accepted April 23, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Jay A. Harolds, MD, Division of Radiology and Biomedical Imaging, College of Human Medicine, Michigan State University, Advanced Radiology Services, PC, 3264 North Evergreen Dr. NE, Grand Rapids, MI 49525. E-mail: harolds112@cox.net. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

18F-FDG Whole-body PET/MRI of a 30-Week Pregnant Woman With Breast Cancer Revealed Interesting Fetal Findings A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body 18F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of neoadjuvant chemotherapy. Received for publication March 19, 2019; revision accepted May 1, 2019. Conflicts of interest and sources of funding: SyMPTOm PET/MRI platform was funded by the Assistance Publique-Hôpitaux de Paris, the Agence Régionale de Santé, and the Cancéropôle Ile-de-France. None declared to all authors. Correspondence to: Paul Blanc-Durand, MD, MSc, Department of Nuclear Medicine, CHU Henri Mondor, 51 avenue du Maréchal De-Lattre-De-Tassigny, Créteil, France. E-mail: paul.blancdurand@aphp.fr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.