Clinical Nuclear Medicine

Minimal-Invasive Robot-Assisted Image-Guided Resection of Prostate-Specific Membrane Antigen–Positive Lymph Nodes in Recurrent Prostate Cancer With the rapid expansion of robot-assisted surgical procedures, the need for robot-compliant image guidance technologies has also increased. Examples hereof are the integrated firefly fluorescence camera, the drop-in ultrasound probe, and the recently introduced DROP-IN gamma probe. Combined with 68Ga–prostate-specific membrane antigen–(PSMA)–11 PET/CT (staging) and 99mTc-PSMA-I&S SPECT/CT (preoperative imaging), the latter DROP-IN gamma probe technology recently allowed us to perform the first clinical cases of robot-assisted PSMA-guided salvage surgery of lymphatic metastases. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Received for publication December 7, 2018; revision accepted March 3, 2019. Conflicts of interest and sources of funding: This research was supported by an NWO-TTW-VICI grant (TTW 16141). Material support was provided by Eurorad (Eurorad S.A., Eckbolsheim, France) supporting our study with a prototype DROP-IN gamma probe. None declared to all authors. Correspondence to: Fijs W. B. van Leeuwen, PhD, Interventional Molecular Imaging Laboratory, Department of Radiology, C2-S zone, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, the Netherlands. E-mail: F.W.B.van_Leeuwen@lumc.nl; or Tobias Maurer, MD, PhD, FEBU, Leitender Arzt, Universitätsklinikum Hamburg-Eppendorf, Martini-Klinik am UKE GmbH, Martinistraße 52 Gebäude Ost 46, 20246 Hamburg, Germany. E-mail: t.maurer@uke.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

FDG PET/CT in a Case of Bilateral Tuberculous Epididymo-orchitis Isolated genital tuberculosis is rare. We present a case of bilateral tuberculous epididymo-orchitis showing high FDG uptake on FDG PET/CT. In addition, the patient had a prostatic FDG-avid lesion, consistent with tuberculous prostatitis. This case indicates tuberculous epididymo-orchitis, especially in tuberculosis-endemic regions, should be considered as a differential diagnosis in patients with hypermetabolic epididymal or testicular lesions, including benign and malignant tumors, bacterial epididymo-orchitis, abscess, idiopathic granulomatous orchitis, and sarcoidosis. Received for publication March 4, 2019; revision accepted March 21, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Pengcheng Ran, MM, Department of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou 510120, Guangdong Province, China. E-mail: cmurpc@163.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

64CuCl2 PET/CT in a Hyperfunctioning Parathyroid Gland We report a case of incidental 64CuCl2 uptake at PET/CT imaging in a 61-year-old man with a biochemical recurrence of prostate cancer. Parathyroid hormone was slightly elevated (92.4 pg/mL; reference range, 18.4–80.1 pg/mL); serum calcium was in reference range (9.5 mg/dL; reference range, 8.6–10.6 mg/dL), whereas serum phosphate was slightly low (2.6 mg/dL; reference range, 2.7–4.5 mg/dL). This case highlights the ability of 64CuCl2, similar to radiolabeled choline, to identify the presence of hyperfunctioning parathyroid glands in patients undergoing PET/CT examination. Received for publication January 12, 2019; revision accepted March 24, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Laura Evangelista, MD, PhD, Nuclear Medicine Unit, Veneto Institute of Oncology IOV–IRCCS, Via Gattamelata, 64 35128 Padova, Italy. E-mail: laura.evangelista@iov.veneto.it. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

18F-FACBC PET/MRI in Diagnostic Assessment and Neurosurgery of Gliomas Purpose This pilot study aimed to evaluate the amino acid tracer 18F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas. Materials and Methods Eleven patients with suspected primary or recurrent low- or high-grade glioma received an 18F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference. Results Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5–2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%). Conclusions Low- versus high-grade glioma differentiation may be possible with 18F-FACBC using TBR. 18F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate 18F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Received for publication January 23, 2019; revision accepted March 24, 2019. Conflicts of interest and sources of funding: This work was supported by the Norwegian National Advisory Unit for Ultrasound and Image Guided Therapy, St Olavs Hospital, Trondheim, Norway. The authors report no conflicts of interest. Correspondence to: Anna Karlberg, MSc, Department of Radiology and Nuclear Medicine, St Olavs Hospital, Olav Kyrres gt 17, N-7006 Trondheim, Norway. E-mail: annamka@stud.ntnu.no. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Compressed Central Zone Uptake on PSMA PET/CT—A Potential Pitfall in Interpretation The case of a 66-year-old man undergoing a staging PSMA PET/CT after a recent diagnosis of prostate carcinoma is presented. In addition to uptake within the prostate consistent with primary tumor activity, mild symmetrical and diffuse uptake is also noted within central zone. The appearance is not consistent with likely tumor activity. Comparison is made with histopathology after a radical prostatectomy, and no correlating tumor is noted in the region of central zone uptake. Increased PSMA uptake within the compressed central zone of the prostate may represent a potential pitfall in PSMA PET/CT imaging. Received for publication August 15, 2018; revision accepted March 24, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Rueben Ganeshalingam, MBBS, Nuclear Medicine, Royal North Shore Hospital, Reserve Rd, St Leonards, New South Wales, Australia 2065. E-mail: Rueben.ganeshalingam@health.nsw.gov.au. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Complete Metabolic Response Assessed by FDG PET/CT to FOLFIRI-Aflibercept in Second-Line Treatment of Metastatic Colorectal Cancer FOLFIRI-aflibercept chemotherapy is indicated in second-line treatment of metastatic colorectal cancer (mCRC) after progression under FOLFOX (±bevacizumab). Nevertheless, its proven therapeutic efficacy in clinical trials was based on partial responses. And to date, only 2 cases of complete response assessed by CT were reported in literature. We report a complete metabolic response assessed by FDG PET/CT in a 50-year-old woman with mCRC treated by FOLFIRI-aflibercept. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC. Received for publication December 2, 2018; revision accepted March 26, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Karim Amrane, MD, Department of Oncology, University Hospital of Brest, 2 Ave Foch, 29609 Brest Cedex, France. E-mail: karim.amrane@chu-brest.fr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Critical Assessment of the Linear No-Threshold Hypothesis: Its Validity and Applicability for Use in Risk Assessment and Radiation Protection The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region. Received for publication February 20, 2019; revision accepted March 27, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Bennett S. Greenspan, MD, MS, 150 River Club Lane, North Augusta, SC 29841. E-mail: bengreenspan0708@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Predictive Value of 16α-[18F]-Fluoro-17β-Estradiol PET as a Biomarker of Progestin Therapy Resistance in Patients With Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer For early-stage endometrial cancer patients who wish to preserve fertility, progestin treatment is effective. However, repeated endometrial curettage to evaluate treatment response may cause infertility. The clinical courses of 3 patients who were treated with fertility-sparing progestin treatment and underwent serial 18F-FES PET before and after treatment are presented. The SUVmean decreased greatly in patients with pathologically complete response (44.2%, 46.2%), whereas there was only a small change (22.5%) in the patient with pathologically stable disease who finally underwent hysterectomy. 18F-FES PET can be a noninvasive method to evaluate response to fertility-sparing progestin treatment. Received for publication November 14, 2018; revision accepted March 25, 2019. Conflicts of interest and sources of funding: This study was partly supported by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (nos. 15H04981, 16K20181, and 16K10345). None declared to all authors. Correspondence to: Hideaki Tsuyoshi, MD, Department of Obstetrics and Gynecology, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. E-mail: go242h@yahoo.co.jp. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Critical Assessment of the Linear No-Threshold Hypothesis: What Is the Evidence? The Linear No-Threshold (LNT) hypothesis regarding low-level radiation is based on expert opinion. As more experts critically evaluate the absence of convincing evidence supporting the LNT hypothesis, the more likely we will recognize that LNT may create more risk than it mitigates. Received for publication March 28, 2019; revision accepted March 29, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Patrick M. Colletti, MD, FACNM, FSNMMI, Keck School of Medicine of USC, 1500 San Pablo St, Los Angeles, CA 90033. E-mail: colletti@usc.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Thyroid Cancer Brain Metastasis: Survival and Genomic Characteristics of a Large Tertiary Care Cohort Purpose Brain metastases (BMs) in patients with differentiated thyroid cancer (DTC) are rare but associated with poor prognosis. We examined risk factors for overall survival (OS) in this population and explored the pattern of genomic alterations. Methods Single-institution, retrospective review of all patients with DTC from January 2000 to November 2016 identified 79 patients for analysis. Multiple prognostic factors, including age, gender, distal metastasis (DM), diagnosis time, DM sites, BM diagnosis time, BM number and size, genomic sequencing data, craniectomy, external beam radiation therapy, and kinase inhibitor therapies, were evaluated. Univariate and multivariate analyses were performed. Results Median survival after BM was 18 months. One- and 3-year survival rates were 63% and 33%, respectively. Univariate analysis identified 4 covariates correlated with prolonged survival: time between DTC diagnosis and BM for less than 3 years (P = 0.01), time from initial DM diagnosis to BM for 22 months or less (P = 0.03), 3 BM sites or fewer (P = 0.002), and craniectomy (P = 0.05). Multivariate model revealed 3 variables associated with OS: DTC diagnosis to BM time of less than 3 years (P = 0.04), craniectomy (P = 0.06), and patients with fewer than 3 BM sites (P = 0.06). The majority of patients with BM had a telomerase reverse transcriptase promoter mutation, However, mutational status was not an independent predictor of survival. Conclusions For BM from DTC, time interval between DTC diagnosis and BM, number of BM sites, and craniectomy were independently associated with OS. Further studies are needed to define the role of genomic mutations in advanced cancer. Received for publication October 26, 2018; revision accepted March 30, 2019. J.R.O. and J.D.K., co–first authors, contributed equally to this work. 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 (to J.R.O., R.K.G., S.M.L.), as well as by the Center for Targeted Radioimmunotherapy and Diagnosis and the Ludwig Center for Title page 2 Cancer Immunotherapy. This research was also funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support grant P30 CA008748. The authors declare no conflict of interest. Correspondence to: Joseph R. Osborne, MD, PhD, Department of Radiology, New York–Presbyterian Weill Cornell Medical Center, 520 E 70th St, Starr-2, New York, NY 10021. E-mail: jro7001@med.cornell.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
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alsfakia@gmail.com