99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer Objective This study aims to investigate the value of 99mTc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). Methods A total of 125 patients with biochemical recurrence of prostate cancer underwent 99mTc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)–positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent 99mTc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. Results Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent 99mTc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43–0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20–0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07–0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38–0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13–0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0–0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. Conclusions The results of our study show that 99mTc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1. Received for publication January 17, 2020; revision accepted April 4, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Christian Schmidkonz, MD, Clinic of Nuclear Medicine, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. E-mail: christian.schmidkonz@uk-erlangen.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Rare Case of Testicular Sarcoidosis Detected on FDG PET/CT in a Patient With PUO Genitourinary sarcoidosis is an uncommon entity, and testicular sarcoidosis is even rarer. We present a case of 66-year-old man who presented to our hospital as PUO (pyrexia of unknown origin) and later diagnosed as testicular sarcoidosis with the help of FDG PET/CT. Received for publication January 12, 2020; revision accepted April 10, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Girish Kumar Parida, MD, Department of Nuclear Medicine and PET/CT, Tata Main Hospital, Jamshedpur 831001, India. E-mail: grissh135@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Lenograstim-Induced Nodal Extramedullary Hematopoiesis: A Challenging Diagnosis in Lymphoma Evaluation With: 18: F-FDG PET/CT We report the case of a 23-year-old man with nodal EMH (extramedullary hematopoiesis) occurring during treatment for a stage IIA “gray-zone” lymphoma. Although it is often related to myeloproliferative bone marrow disease, benign etiologies such as lenograstim treatment after chemotherapy can also induce EMH and be responsible for false-positive 18F-FDG PET/CT examinations. In this respect, GLUT overexpression in hematopoietic lineages and macrophages of the inflammatory environment are responsible for increased 18F-FDG uptake. Histopathologic confirmation of new hypermetabolic lesions on follow-up PET/CT may be required when the new lesions do not conform with the treatment responses in the preexisting lesions. Received for publication January 30, 2020; revision accepted April 8, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Benjamin Leroy-Freschini, MD, Department of Nuclear Medicine and Molecular Imaging, ICANS, 17, Rue Albert Calmette, BP 23025, 67033 Strasbourg Cedex, France. E-mail: b.leroy-freschini@icans.eu. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Pitfalls in the Detection of Insulinomas With Glucagon-Like Peptide-1 Receptor Imaging Purpose Physiological pancreaticoduodenal uptake of radiolabeled exendin-4 in Brunner glands of the proximal duodenum is the most common pitfall for false interpretation of glucagon-like peptide-1 receptor (GLP-1R) imaging. The aim of this study was to analyze the pancreaticoduodenal uptake in GLP-1R PET/CT and SPECT/CT images and to identify additional potential reading pitfalls in patients with suspected insulinoma. Methods A post hoc analysis of a prospective study, including 52 consecutive patients, was performed. All patients underwent 1 68Ga-exendin-4 PET/CT and 2 111In-exendin-4 SPECT/CT scans (4 and 72 hours postinjection) in a randomized crossover order. Three board-certified nuclear medicine physicians read all scans independently. They were unaware of other results. Reference standard was surgery with histopathological confirmation of an insulinoma/nesidioblastosis and normalization of blood glucose levels after surgery. Results There were no false-positive readings. However, there were a number of false-negative PET/CT and SPECT/CT readings, respectively: (1) due to false interpretation of uptake in the pancreaticoduodenal region (falsely interpreted as physiological uptake in Brunner glands instead of an insulinoma in 0.6% vs 9.0%), (2) due to ectopic insulinoma (0% vs 2.6%), (3) due to small insulinoma (1.9% vs 5.1%), (4) due to insulinoma overlap with kidneys (1.9% vs 4.5%), and (5) due to nesidioblastosis (0.6% and 1.9%). Pitfalls were identified in all GLP-1R PET/CT and SPECT/CT scans. Conclusions Peripancreatic uptake, small size of an insulinoma, insulinoma overlap with kidneys, and presence of nesidioblastosis are potential pitfalls in GLP-1R imaging, which can lead to false reading results. Received for publication February 27, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: The study was supported by the Swiss National Science Foundation (grant 320030-152938) and the Desirée and Niels Yde’s Foundation (grant 389-12), which had no role in study design, data collection, analysis, interpretation, or writing of the report. No conflict of interest for all authors. The study was approved by the regional scientific ethics committee, and all procedures performed in studies involving human participants were in accordance with the ethical standards of the regional scientific ethics 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. Correspondence to: Damian Wild, MD, PhD, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, 4053 Basel, Switzerland. E-mail: damian.wild@usb.ch. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Superior Vena Cava Syndrome Induced Collateral Circulation on 99mTc–Macroaggregated Albumin Lung Perfusion Scintigraphy Perfusion lung scintigraphy using SPECT/CT is one mainstay in diagnosing pulmonary embolism. Although typically almost all tracer will be accumulated in the lung capillaries, occasionally abnormal uptake can be detected. As superior vena cava syndrome leads to aberrant blood flow, tracer injected to an arm vein might partly circumvent the pulmonary capillary bed and accumulate in well-perfused anatomical structures. In this case, next to the commonly described liver enhancement, more prominent pseudo-uptake of various thoracic vertebrae was observable. However, a time-related FDG PET/CT demonstrated only the hepatic pseudo-uptake. Taken together, careful assessment of superior vena cava syndrome patient studies is highly recommended. Received for publication January 21, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: David Kersting, MD, MSc, Department of Nuclear Medicine, University Hospital Essen, D-45147 Essen, Germany. E-mail: david.kersting@uk-essen.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients Purpose The primary aim of this multicenter retrospective analysis is to examine the role of 18F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive 18F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. Materials and Methods This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent 18F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. Results 18F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008–2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. Conclusions 18F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of 18F-choline images and in patient selection in the last 5 years. Received for publication March 10, 2020; revision accepted April 19, 2020. Conflicts of interest and sources of funding: none declared. Ethical statement: all patients gave their informed consent to 18F-choline PET/CT examination. Correspondence to: Laura Evangelista, MD, PhD, Nuclear Medicine, Department of Medicine–DIMED, University of Padua, Via Giustiani, 2 35128 Padua, Italy. E-mail: laura.evangelista@unipd.it. 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 © 2020 Wolters Kluwer Health, Inc. All rights reserved.

PET/CT-Guided Tissue Sampling in Patients With a Failed or Inconclusive CT-Guided Procedure: Outcomes and Contributing Factors Background CT-guided tissue sampling is a very effective tool. However, false-negative results are obtained when regions such as necrotic core or surrounding reactive fibrosis and inflammation are sampled. PET/CT-guided sampling can circumvent these limitations. Purpose The aim of this study was to analyze the effectiveness of PET/CT-guided sampling in patients with at least 1 instance of failed or inconclusive CT-guided procedure and factors determining the accurate sampling and complications. Methods One hundred eleven patients were prospectively included. After feasibility analysis in a diagnostic 18F-FDG PET/CT, sampling was performed in 106 patients (45 women, 61 men; mean age, 48.09 ± 15.42 years; biopsy in 80 and fine-needle aspiration cytology [FNAC] in 26 patients), using robotic arm and a lower IV injection dose of 74 to 111 MBq (2–3 mCi) 18F-FDG. In all patients, final check scans revealed needle at the target site. Using planned needle path as reference, deviations in first check scan were measured. Patient (n = 30) and respiratory motion (n = 57) were also recorded. Results Accurate lesion targeting was achieved in 81 cases (63 positive lesions, 12 confounding lesions, and 7 inadequate samples). Lesion was missed in 5 instances, and blood/necrotic tissue sampled in 19. Overall 18F-FDG–avid lesions were accurately targeted in 77.36% of patients (86.25% [biopsy] + 50% [FNAC]). Significant variables affecting targeting were needle gauge, deviation from intended entry point, procedure duration, procedure type, and patient movement. Using binomial regression, the significant parameters were procedure type (biopsy vs FNAC; odds ratio [OR], 5.916; P = 0.002), patient movement (OR, 0.275; P = 0.023), and procedure duration (OR, 1.195; P = 0.011). Overall complication rate was 21.70%, with 4.71% major complications. It was dependent on target depth (mean depth, 69.74 ± 20.29 mm [complications] vs 47.18 ± 22.60 mm; P < 0.001). Positive correlation was seen between the target depth and distance of needle from the intended target (Spearman ρ = 0.307; P = 0.001). In 28 procedures, the physician was asked to wear a pocket dosimeter, who received a mean dose of 2.52 (SD, 3.10) μSv. Conclusions PET/CT-guided sampling should be considered where CT-guided biopsy has failed or is inconclusive. The outcome is impacted by needle gauge and patient movement, and complication rate is dependent on target depth. Received for publication November 22, 2019; revision accepted April 19, 2020. The study was performed done in All India Institute of Medical Sciences, New Delhi, India. Conflicts of interest and sources of funding: none declared. Rakesh Kumar and Anshul Sharma contributed equally to this work. Correspondence to: Anshul Sharma, MD, Department of Nuclear Medicine, All India Institute of Medical Sciences, Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, India 110029. E-mail: anshul.aiims@gmail.com. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee (approval no. IESC/T-137/01.04.2011) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent (with translation in patients’ native language) was taken from every patient. This consent form and its translation were approved by the institutional ethical committee before the initiation of the study. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A Case of Localized Malignant Peritoneal Mesothelioma With Lung Cancer Detected by 18F-FDG PET/CT A 62-year-old woman was referred for cough and lower abdominal pain. 18F-FDG PET/CT showed strong uptake not only in the left lung mass and hilar and mediastinal lymph nodes, but also a huge lower abdominal mass. All lesions were initially thought to be multiple metastases because bronchial biopsy of the lung mass showed poorly differentiated adenocarcinoma. However, the abdominal mass was found to be malignant peritoneal mesothelioma after surgical resection. It was difficult to diagnose this case correctly before resection because localized malignant peritoneal mesothelioma is rare. Received for publication February 5, 2020; revision accepted April 18, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Shotaro Kobayashi Shimizu, MD, 2-10-39 Shibata, Kita-Ku, Osaka 530-0012, Japan. E-mail: shotaro.kb.shimizu@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Prominent Bone Marrow Metastases Without Concurrent Intra-Chest Metastasis in a Case of Cardiac Angiosarcoma Primary cardiac angiosarcoma is rare and often advances by dissemination. Lungs are the most common metastatic sites, especially when the tumor originates in the right side of the heart. Bone metastases from cardiac angiosarcoma very rarely occur without concurrent pulmonary metastases. We report a case of cardiac angiosarcoma having prominent bone metastases without concurrent pulmonary lesions, as demonstrated by FDG PET/CT scan. Conflicts of interest and sources of funding: none declared. Received for publication February 28, 2020; revision accepted April 18, 2020. Correspondence to: Xiaohong Ou, MD, Department of Nuclear Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu 610041, Sichuan, People’s Republic of China. E-mail: Xuqinmao@126.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Widespread Skin Infiltration of Leukemia Cutis on 18F-FDG PET/CT A 67-year-old man experienced multiple cutaneous nodules for 3 weeks. His initial skin biopsy only showed local inflammation. However, after a 2-week anti-inflammation therapy, the skin manifestations were not improved while the leukocyte count gradually increased. FDG PET/CT revealed widespread cutaneous and subcutaneous hypermetabolic lesions in many parts of the body, and heterogeneously increased uptakes in the bone marrow. Bone marrow biopsy and second skin biopsy were performed. Pathological examination from both specimen demonstrated acute monocytic leukemia. Received for publication February 25, 2020; revision accepted April 22, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Weibing Miao, MD, PhD, Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Rd, Fuzhou, 350005, Fujian, China. E-mail: miaoweibing@126.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.