Clinical Nuclear Medicine

Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-L-Tyrosine PET Purpose PET/CT using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). Methods Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. Results 18F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. Conclusions Irrespective of the analytical approach, 18F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers. Received for publication December 18, 2018; revision accepted April 11, 2019. P.T.M. and C.L. contributed equally to this work. Informed consent was obtained from all individual participants included in the study. 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. Conflicts of interest and sources of funding: none declared. Authorship: Conception and design: O.K., M.I.M., T.L., A.F.K., P.T.M., C.L. Development of methodology: O.K., M.K., J.B., S.S., M.L., P.T.M., C.L. Acquisition of data: O.K., M.I.M., M.K., J.B., C.M.M., C.L. Analysis and interpretation of data: O.K., M.I.M., J.T.-G., J.B., C.M.M., C.L. Writing, review and/or revision of the manuscript: all authors. Administrative, technical, or material support: J.T.-G., S.S., R.-I.E., M.L., P.T.M. Supervision: R.-I.E., M.L., P.T.M., C.L. Correspondence to: Constantin Lapa, MD, Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 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-DCFPyL PET/CT in a Single Large Metastasis With Prostate-Specific Antigen Level of 856 ng/mL Literature shows that prostate-specific membrane antigen (PSMA) PET/CT may detect biochemical recurrence of prostate cancer at low prostate-specific antigen (PSA) levels, including detection of oligometastatic disease and hence direct metastasis-directed therapy. Although it is generally accepted that higher PSA values indicate higher disease burden, few data are available on the relation between PSA levels and number of detected metastases on PSMA PET/CT. This report demonstrates a patient with high PSA levels (856 ng/mL) at time of biochemical recurrence that showed only 1 metastasis on PSMA PET/CT. Combined androgen deprivation therapy and radiation therapy resulted in a complete biochemical response. Received for publication March 5, 2019; revision accepted May 19, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Maurits Wondergem, MD, PhD, Wilhelminalaan 12 1815 JD Alkmaar, the Netherlands. E-mail: M.wondergem@nwz.nl. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

High-Resolution PET Cisternography With 64Cu-DOTA for CSF Leak Detection Intracranial hypotension may lead to chronic, debilitating symptoms, and severe complications. The underlying CSF leak may be difficult to localize. To establish a new diagnostic option for the detection of CSF leaks, 64Cu-DOTA was developed as a tracer for PET imaging. PET/CT imaging was possible with high resolution and without complications. In one patient, the exact site of a dural tear was identified, enabling successful surgical treatment. PET cisternography with 64Cu-DOTA appears to be safe and able to locate a CSF leak. It has the potential to be a problem-solving modality in cases with inconclusive CT, MR, and/or scintigraphic findings. Received for publication February 8, 2019; revision accepted May 19, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Martin Freesmeyer, MD, Clinic of Nuclear Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. E-mail: martin.freesmeyer@med.uni-jena.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Stepwise Approach to Identify the Clinical Role of 18F-FDG PET/CT in Patients With Suspicious Bone Metastasis From an Unknown Primary Site In patients with suspicious bone metastasis, the clinical impact of PET/CT for differential diagnosis and primary lesion identification could differ according to 18F-FDG uptake patterns. We report the findings in patients with suspicious bone metastasis who underwent PET/CT for the evaluation of the primary lesion site and were classified in a stepwise manner, first based on the multiplicity of positive bone uptake and then the presence of extraskeletal uptake. Received for publication December 4, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: This study was supported by a grant from KOICA and the Chonnam National University Hwasun Hospital Institute for Biomedical Science (HCRI 17 922-21). None declared to all authors. Correspondence to: Seong Young Kwon, MD, PhD, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, 58128, Republic of Korea. E-mail: kwonsy@jnu.ac.kr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Celiac Disease on FDG PET/CT An FDG PET with diagnostic CT was performed on a 52-year-old man for investigation of lymphocytosis and the clinical suspicion of lymphoma. The PET/CT demonstrated diffuse small bowel uptake, prominent mesenteric lymph nodes without significant FDG uptake, and other features suggestive of celiac disease. Subsequently, the patient was found to have markedly elevated celiac disease antibodies (deamidated gliadin IgG and tissue transglutaminase IgA) and to be HLA DQ2 and DQ8 allele positive on genotyping for celiac disease. Gastroscopy and duodenal biopsy also confirmed the diagnosed. Received for publication December 18, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Anthony Cardin, MBBS, Barwon Medical Imaging, University Hospital Geelong, Ryrie St, Geelong, Victoria, 3220, Australia. E-mail: ancardin@barwonhealth.org.au. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ileal Neuroendocrine Tumor With Bilateral Breast and Ovarian Metastases: Findings on 68Ga-DOTANOC PET/CT Scan Metastasis to the breast is a rare occurrence and constitutes less than 2% of all breast tumors. Similarly, ovarian metastases from neuroendocrine tumors are also uncommon, and if the adnexal masses are bilateral, then the chances of it being metastatic rather than being primary range from 88% to 94%. We present a case of 61-year-old woman who in the course of workup for abdominal pain and diarrhea was eventually diagnosed as ileal neuroendocrine tumor with breast, ovarian, and lymph nodal metastases on 68Ga-DOTANOC PET/CT scan. Received for publication December 30, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: none declared. Correspondence: Girish Kumar Parida, MD, Nuclear Medicine, Department of Nuclear Medicine, Delhi Institute of Functional Imaging, Hauz Khas, New Delhi 110016. E-mail: grissh135@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Adult Pancreatoblastoma With Liver Metastasis Diagnosed by 18F-FDG PET/CT and 2 Years' Postoperative Follow-up Pancreatoblastoma is an extremely rare malignant tumor of the pancreas. Most patients are infants and children; however, a few cases have been reported in adults. Herein, we present the case of a 49-year-old man with pancreatoblastoma and liver metastasis who underwent preoperative multimodal imaging, in which 18F-FDG PET/CT showed a markedly increased 18F-FDG uptake in the metastatic lesion and a slightly increased uptake in the primary lesion. Subsequently, the patient underwent complete resection of the primary and metastatic lesions. No recurrences or metastases were found in 2 years of follow-up. Received for publication March 27, 2019; revision accepted May 13, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Shu-Xia Wang, MD, PhD, Room 517, 5/F Weilun Building, Guangdong Provincial People's Hospital, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China. E-mail: shuxia_wangGGH@outlook.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Adenocarcinoma of the Stomach Leading to Recurrent Regurgitation and Muscular Hypermetabolism on 18F-FDG PET/CT Skeletal muscle uptake of 18F-FDG can result from a variety of physiologic and pathologic conditions. It is important for the physician to interpret these uptake patterns in the correct context to avoid a misdiagnosis. We present a case of a 36-year-old man with progressive, repeated episodes of regurgitation who was diagnosed with adenocarcinoma of the stomach. 18F-FDG PET/CT showed increased tracer uptake in the primary tumor and in the intercostal and sternocleidomastoid muscles. The pattern of tracer uptake along with the clinical history and examination of the patient helped differentiate a physiologic variant from a pathologic cause. Received for publication April 15, 2019; revision accepted May 11, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Bhagwant Rai Mittal, MD, DNB, Department of Nuclear Medicine, Ground Floor, A-Block, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. E-mail: brmittal@yahoo.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Evaluation of Lung Cancer and Neuroendocrine Neoplasm in a Single Scan by Targeting Both Somatostatin Receptor and Integrin αvβ3 Purpose This pilot study aimed to prove the complementary value of a novel 68Gallium-labeled heterodimeric peptide, 68Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvβ3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC). Methods With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo 68Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent 68Ga-NOTA-TATE PET/CT, the SCLC patients underwent 68Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent 18F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison. Results In the primary tumors of NSCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of 18F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of 68Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of 18F-FDG (3.56 ± 0.74, P = 0.1833). Conclusions This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan. Received for publication November 12, 2018; revision accepted May 9, 2019. Conflicts of interest and sources of funding: This study was partly supported by the Key Special Project on Inter-Governmental Scientific and Technological Innovation Cooperation in National Key Research and Development Plan (2016YFE0115400), the Chinese Academy of Medical Science Major Collaborative Innovation Project (2016-I2M-1-011), National Nature Science Foundation (81741142, 81871392), and Beijing Municipal Natural Science Foundation (7161012). None declared to all authors. Correspondence to: Zhaohui Zhu, MD, Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, People's Republic of China. E-mail: zhuzhh@pumch.cn. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Giant Melanotic Malignant Peripheral Nerve Sheath Tumor in the Pelvis: Contrast-Enhanced CT and 18F-FDG PET/CT Finding Melanotic malignant peripheral nerve sheath tumor is an extremely rare tumor, which originates from the neural crest, and more than half the cases are associated with Carney complex (myxomas, spotty pigmentation, and endocrine abnormalities). Herein, we have presented a case of a melanotic malignant peripheral nerve sheath tumor, which is not associated with Carney complex. The patient underwent preoperative nonenhanced CT, contrast-enhanced CT, and 18F-FDG PET/CT scans, which showed a large pelvic tumor with heterogeneous enhancement and increased 18F-FDG uptake. Subsequently, the patient underwent complete resection of the tumor. Received for publication April 4, 2019; revision accepted May 7, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Shuxia Wang, MD, PhD, Room 517, 5/F, WeiLun Building of Guangdong Provincial People's Hospital, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, People's Republic of China. E-mail: shuxia_wangGGH@outlook.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
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