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      Detection Efficacy of 18F-PSMA-1007 PET/CT in 251 Patients with Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

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          Abstract

          Prostate-specific membrane antigen (PSMA)–targeted PET imaging recently emerged as a new method for the staging and restaging of prostate cancer. Most published studies investigated the diagnostic potential of 68Ga-labeled PSMA agents that are excreted renally. 18F-PSMA-1007 is a novel PSMA ligand that has excellent preclinical characteristics and that is only minimally excreted by the urinary tract, a potential advantage for pelvic imaging. The aim of this study was to investigate the diagnostic efficacy of 18F-PSMA-1007 for biochemical recurrence (BCR) after radical prostatectomy. Methods: From 3 academic centers, 251 patients with BCR after radical prostatectomy were evaluated in a retrospective analysis. Patients who had received second-line androgen deprivation therapy (ADT) or chemotherapy were excluded, but prior first-line ADT exposure was allowed. The median prostate-specific antigen (PSA) level was 1.2 ng/mL (range, 0.2–228 ng/mL). All patients underwent PSMA PET/CT at 92 ± 26 min after injection of 301 ± 46 MBq of 18F-PSMA-1007. The rate of detection of presumed recurrence sites was correlated with the PSA level and original primary Gleason score. A comparison to a subset of patients treated previously with ADT was undertaken. Results: Of the 251 patients, 204 (81.3%) had evidence of recurrence on 18F-PSMA-1007 PET/CT. The detection rates were 94.0% (79/84), 90.9% (50/55), 74.5% (35/47), and 61.5% (40/65) for PSA levels of greater than or equal to 2, 1 to less than 2, 0.5 to less than 1, and 0.2 to less than 0.5 ng/mL, respectively. 18F-PSMA-1007 PET/CT revealed local recurrence in 24.7% of patients ( n = 62). Lymph node metastases were present in the pelvis in 40.6% of patients ( n = 102), in the retroperitoneum in 19.5% of patients ( n = 49), and in supradiaphragmatic locations in 12.0% of patients ( n = 30). Bone and visceral metastases were detected in 40.2% of patients ( n = 101) and in 3.6% of patients ( n = 9), respectively. In tumors with higher Gleason scores (≤7 vs. ≥8), detection efficacy trended higher (76.3% vs. 86.7%) but was not statistically significant ( P = 0.32). However, detection efficacy was higher in patients who had received ADT (91.7% vs. 78.0%) within 6 mo before imaging ( P = 0.0179). Conclusion: 18F-PSMA-1007 PET/CT offers high detection rates for BCR after radical prostatectomy that are comparable to or better than those published for 68Ga-labeled PSMA ligands.

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          F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients

          Purpose The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18F-PSMA-1007 in human volunteers and patients. Methods Radiation dosimetry of 18F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent 18F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining. Results With an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, 18F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. 18F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. Conclusion 18F-PSMA-1007 performs at least comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68Ga-labelled PSMA-targeted tracers. Electronic supplementary material The online version of this article (doi:10.1007/s00259-016-3573-4) contains supplementary material, which is available to authorized users.
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            Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer.

            Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of (18)F-DCFBC in men with metastatic PCa. Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of (18)F-DCFBC. Serial PET was performed until 2 h after administration. Time-activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radioactivity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Although further studies are needed for validation, our findings demonstrate the potential of (18)F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for (18)F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as (18)F-FDG.
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              [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH.

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                Author and article information

                Journal
                J Nucl Med
                J. Nucl. Med
                jnumed
                jnm
                Journal of Nuclear Medicine
                Society of Nuclear Medicine
                0161-5505
                1535-5667
                March 2019
                March 2019
                : 60
                : 3
                : 362-368
                Affiliations
                [1 ]Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany
                [2 ]German Cancer Consortium (DKTK), Heidelberg, Germany
                [3 ]CCU Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [4 ]Department of Nuclear Medicine, Technical University Munich, Munich, Germany
                [5 ]Department of Urology, Technical University Munich, Munich, Germany
                [6 ]Division of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [7 ]Department of Radiation Oncology, Technical University Munich, Munich, Germany
                [8 ]Center of Nuclear Medicine, PositronMed, FALP, Santiago, Chile; and
                [9 ]Molecular Imaging Program, National Cancer Institute, Bethesda, Maryland
                Author notes
                For correspondence or reprints contact: Frederik L. Giesel, Department of Nuclear Medicine, Heidelberg University Hospital INF 400, 69120 Heidelberg, Germany. E-mail: frederik@ 123456egiesel.com

                Published online Jul. 24, 2018.

                Article
                212233
                10.2967/jnumed.118.212233
                6424235
                30042163
                37e498ea-2b23-471b-8cf0-e9bc63ce2abf
                © 2019 by the Society of Nuclear Medicine and Molecular Imaging.

                Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.

                History
                : 02 April 2018
                : 23 June 2018
                Page count
                Pages: 7
                Categories
                Theranostics
                Clinical

                18f-psma-1007,pet/ct,hybrid imaging,prostate cancer,biochemical recurrence

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