PSMA-Ligand PET for Early Castration-Resistant Prostate Cancer: A Retrospective Single-Center Study

Weber, Manuel; Kurek, Claudia Ewa; Barbato, Francesco; Eiber, Matthias; Maurer, Tobias; Nader, Michael; Hadaschik, Boris; Grünwald, Viktor; Herrmann, Ken; Wetter, Axel; Fendler, Wolfgang P.

doi:10.2967/jnumed.120.245456

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…Although some studies show that long-term use of ADT has no effect on 68 Ga-PSMA PET/CT, Afshar-Oromieh et al found that use of long-term ADT could reduce the PSMA uptake and the visibility of tumour lesions in castration-sensitive prostate cancer (8,9). Weber et al observed that 68 Ga-PSMA PET/CT were positive in 75% of early CRPC patients (10). These studies show that many CRPC patients might have negative 68 Ga-PSMA PET/CT findings.…”

Section: Introductionmentioning

confidence: 99%

The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

et al. 2021

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Purpose:The 68 Ga-prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between 68 Ga-PSMA and 18 F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of 18 F-FDG PET/CT compared to 68 Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional 18 F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both 68 Ga-PSMA and 18 F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results:Although both the detection rate (75.0% vs. 51.8%, P=0.004) and positive lesion number (135 vs. 95) of 68 Ga-PSMA PET/CT were higher than 18 F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P=0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and prostate specific antigen (PSA, ≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P=0.01 and P=0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and 3 PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion:Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional 18 F-FDG PET/CT.

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Section: Introductionmentioning

confidence: 99%

The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

et al. 2021

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“…Recent reports on cancer statistics show that prostate cancer (PCa) is the second most common cancer diagnosed in men and fifth leading cause of cancer-related deaths worldwide. , PSMA is overexpressed in hormone-refractory and metastatic prostate cancer and is an excellent target for the diagnostic and therapeutic applications. , Many 68 Ga-labeled PET imaging agents targeting PSMA expression for diagnosis of prostate cancer have been successfully tested clinically, including [ 68 Ga]Ga-PSMA-11, [ 68 Ga]Ga-PSMA-THP, [ 68 Ga]Ga-PSMA-I&T, [ 68 Ga]Ga-PSMA-617, , and [ 68 Ga]Ga-PSMA-093 (Figure ). There are several advantages of using HBED instead of commonly employed DOTA and NOTA for chelating Ga(III).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of ⁶⁸Ga- and ¹⁷⁷Lu-Labeled (R)- vs (S)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives

Zhao

Plöessl²,

Zha³

et al. 2020

Mol. Pharmaceutics

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Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and therefore is an attractive target for prostate cancer diagnosis and radionuclide therapy. Recently, published results from clinical studies using a new PSMA-targeting PET imaging agent, [68Ga]Ga-PSMA-093 ([68Ga]Ga-HBED-CC-O-carboxymethyl-Tyr-CO-NH-Glu), support the development of this agent for the diagnosis of prostate cancer. In this study, the HBED-CC chelating group in PSMA-093 was replaced by stereoselective (R)- or (S)-DOTAGA. This chelating group serves not only for chelating 68Ga but is also amendable for complexing other radioactive metals for radionuclide therapy. The corresponding optically pure (R)- and (S)-[68Ga/177Lu]-DOTAGA derivatives, (R)-[68Ga/177Lu]-13 and (S)-[68Ga/177Lu]-13, were successfully prepared. Comparison of radiolabeling, binding affinity, cell uptake, and biodistribution between the two isomers was performed. Radiolabeling of (R)-[177Lu]Lu-13 and (S)-[177Lu]Lu-13 at 50 °C suggested that rates of complex formation were time-dependent and the formation of (S)-[177Lu]Lu-13 was distinctly faster. The rates of complex formation for the corresponding 68Ga agents were comparable between structural isomers. The natGa and natLu equivalents showed high binding PSMA affinity (IC50 = 24–111 nM), comparable to that of the parent agent, [natGa]Ga-PSMA-093 (IC50 = 34.0 nM). Results of cell uptake and biodistribution studies in PSMA-expressing PC3-PIP tumor-bearing mice appeared to show no difference between the labeled (R)- and (S)-isomers. This is the first time that a pair of [68Ga/177Lu]-(R)- and (S)-DOTAGA isomers of PSMA agents were evaluated. Results of biological studies between the isomers showed no noticeable difference; however, the distinctions on the rate of Lu complex formation should be considered in the development of new 177Lu-DOTAGA-based radionuclide therapy agents in the future.

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“…Especially for recurrent prostate cancer, PSMA PET has demonstrated high sensitivity and specificity for localizing prostate cancer cells in the body (5,6). Growing evidence suggests that PSMA PET is also a useful clinical tool in patients with more advanced prostate cancer (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Repeatability of ⁶⁸Ga-PSMA-HBED-CC PET/CT-derived total molecular tumor volume

et al. 2021

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PSMA-Ligand PET for Early Castration-Resistant Prostate Cancer: A Retrospective Single-Center Study

Cited by 24 publications

References 15 publications

The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

Synthesis and Evaluation of ⁶⁸Ga- and ¹⁷⁷Lu-Labeled (R)- vs (S)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives

Repeatability of ⁶⁸Ga-PSMA-HBED-CC PET/CT-derived total molecular tumor volume

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PSMA-Ligand PET for Early Castration-Resistant Prostate Cancer: A Retrospective Single-Center Study

Cited by 24 publications

References 15 publications

The added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

The added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

Synthesis and Evaluation of 68Ga- and 177Lu-Labeled (R)- vs (S)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives

Repeatability of 68Ga-PSMA-HBED-CC PET/CT-derived total molecular tumor volume

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The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

The added value of ¹⁸F-FDG PET/CT compared to ⁶⁸Ga-PSMA PET/CT in patients with castration-resistant prostate cancer

Synthesis and Evaluation of ⁶⁸Ga- and ¹⁷⁷Lu-Labeled (R)- vs (S)-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives

Repeatability of ⁶⁸Ga-PSMA-HBED-CC PET/CT-derived total molecular tumor volume