Comparative Detection Performance of PSMA and Non-PSMA PET Tracers in Recurrent and Primary Prostate Cancer: A Systematic Review and Network Meta-Analysis

Huang, Yu-Erh MD¹; Huang, Cheng-Kai RT^2; Huang, Ya-Ting RN, NP, PhD³; Tseng, Jing-Ren MD, PhD⁴

¹Department of Nuclear Medicine, Jen-Ai Hospital, Taichung

²Department of Nuclear Medicine, Chung-Kang Branch, Cheng-Ching General Hospital, Taichung

³Primo Biotechnology Co., Ltd, Taipei

⁴Department of Nuclear Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City

Published by Clinical Nuclear Medicine March 25, 2026. 

| DOI: 10.1097/RLU.0000000000006349

Purpose: 

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) tracers have reshaped prostate cancer (PC) imaging, supplementing non-PSMA options such as choline-based agents. However, direct comparative performance data across tracers remain scarce, leaving the optimal choice uncertain. We therefore conducted a systematic review and network meta-analysis (NMA) to assess detection rates (DRs) among PET tracers used for primary and biochemically recurrent PC.

Methods: 

Following PRISMA-NMA guidelines, we systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through March 2025 for studies comparing 2 PET tracers for prostate cancer. The primary outcome was DR, defined as the proportion of PET-positive patients or lesions. Two reviewers independently extracted data on study design, patient demographics, and imaging parameters, and evaluated quality with QUADAS-2. We performed frequentist random-effects NMA to calculate relative risks (RRs) with 95% CIs, using ⁶⁸Ga-PSMA-11 as reference.

Results: 

Nineteen studies (1681 patients) addressed biochemical recurrence, and 6 (271 patients) targeted primary PC, with 2 overlapping. Risk of bias was low for most domains, though some uncertainty remained for reference standards and timing. In biochemically recurrent PC, PSMA-directed tracers achieved higher DRs than non-PSMA probes. Within the PSMA tracers, ⁶⁴Cu-PSMA-617 achieved the highest estimated DR, followed by ¹⁸F-DCFPyL, ¹⁸F-PSMA-1007, and ⁶⁸Ga-PSMA-11. Both ¹⁸F-PSMA-1007 and ¹⁸F-DCFPyL showed higher DRs than ⁶⁸Ga-PSMA-11 in primary and recurrent PC.

Conclusions: 

PSMA tracers outperform non-PSMA alternatives for detecting biochemical recurrence. Among PSMA tracers, ¹⁸F-labeled agents consistently surpass ⁶⁸Ga-PSMA-11 in both biochemically recurrent and primary PC. When available, ¹⁸F-labeled PSMA tracers should be preferred.

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