Current Society of Nuclear Medicine and Molecular Imaging Appropriate Use Criteria (SNMMI, AUC) highlights that all FDA approved tracers and the ones that are undergoing phase III trials are considered to be clinically similar in the staging of prostate cancer (PCa).4 However, with the aim of increasing the ubiquity of PSMA PET imaging globally, there is value in establishing whether radiotracers are truly equivalent. As more evidence becomes available assessing different 18F based radiotracers against [68Ga]Ga-PSMA-11 on both primary staging and restaging following biochemical recurrence, we conducted a systematic review and meta-analysis to collate the study findings.
Our meta-analysis provided important findings assessing intra-individual comparisons as well as matched pair comparisons between 18F and 68Ga tracers. Given that many studies had small sample sizes, our study allowed for a comprehensive assessment of the current tracer landscape. The primary meta-analysed outcome was the lesion SUVmax. Only [18F]DCFPyL and [18F]PSMA-1007 had enough studies reported on them to be meta-analysed on this parameter. The secondary outcome was the benign bone SUVmax of [18F]PSMA-1007 as positive bone uptake is associated with significant clinical impact.5 The effect size was measured by standard difference in means of SUVmax. A paired-sample t-test was used for studies that conducted intra-individual comparisons whereas an independent sample t-test was used for studies that compared [18F]PSMA-1007 or [18F]DCFPyL, and [68Ga]Ga-PSMA-11 in different patient cohorts with matched characteristics. Subgroup analysis for primary staging and restaging after biochemical recurrence (BCR) of PCa was performed. Original investigators were contacted in dealing with missing data hence three more studies were able to be included in the meta-analysis.6 We have provided a qualitative summary of the normal organ SUVmax and the lesion detection rate defined as the number of PSMA avid lesions.
In total, 24 studies met our inclusion criteria. Five different 18F based radiotracers were assessed, including [18F]DCFPyL, [18F]PSMA-1007, [18F]JK-PSMA-7, [18F]rhPSMA-7 and [18F]AlF-PSMA-11. On meta-analysis comparing [18F]DCFPyL with [68Ga]Ga-PSMA-11, we found that they have a high concordance in metastatic lesion detection. The lesion SUVmax is also similar between [18F]DCFPyL and [68Ga]Ga-PSMA-11 from the meta-analysis (standard difference in means = 0.121, 95% CI -0.080 – 0.322). In examining the physiologic organ distribution pattern, we found that [18F]DCFPyL behaves similarly to [68Ga]Ga-PSMA-11. They are both excreted through the urinary tract.
With respect to [18F]PSMA-1007, we observed that it has a greater locoregional lesion detection rate. Our meta-analysis shows that [18F]PSMA-1007 has a greater lesion SUVmax in comparison with [68Ga]Ga-PSMA-11. The standard difference of means was 0.279 (95% CI 0.115 – 0.442). Nevertheless, [18F]PSMA-1007 and [68Ga]Ga-PSMA-11 had a high concordance in both primary staging and restaging of PCa after BCR. There was insufficient data to comment on the clinical impact of the aforementioned SUVmax difference. In examining its normal organ distribution, we found that [18F]PSMA-1007 has a predominant hepatobiliary excretion route. It also has a significantly greater benign bone uptake which may be mistaken as bone lesions (standard difference in means = 1.568, 95% CI 0.403–2.734).
Analysis of [18F]JK-PSMA-7, [18F]rhPSMA-7 and [18F]AlF-PSMA-11 were limited given only one study was reported on each tracer. They all demonstrated marginally greater detection rates in comparison with [68Ga]Ga-PSMA-11, however further studies are required to validate these findings.
In examining the cost of the radiotracers, the production of Gallium-68 was found to be more challenging as it requires an on-site generator.7 The transportation of Gallium-68 from another site is difficult due to its short half-life.7 However, for sites that already have a 68Ge/68Ga generator, cost and access may be cheaper when using Gallium-68 in comparison with Fluorine-18.
We conclude that [18F]DCFPyL is a suitable alternative to [68Ga]Ga-PSMA-11 in PCa staging due to its similar lesion uptake rate with no increase in benign uptakes. However, [18F]PSMA-1007 is less preferable to [68Ga]Ga-PSMA-11 due to its high benign bone uptake which may require additional confirmatory imaging. The main advantage of [18F]PSMA-1007 is its greater locoregional lesion detection rate, which is likely secondary to its predominant hepatobiliary excretion route. However, [68Ga]Ga-PSMA-11 is able to achieve a similar detection rate after administering patients with diuretics pre-scan. Overall, more evidence is needed to compare the radiotracers based on their clinical impacts and logistical considerations.
Written by: Siyu Huang, Department of Surgery, University of Melbourne, Parkville, Victoria, Australia.
References:
- Office of the Commissioner. U.S. Food and Drug Administration. FDA; 2020 [cited 2023 Nov 30]. FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer.
- Center for Drug Evaluation, Research. U.S. Food and Drug Administration. FDA; 2021 [cited 2023 Nov 30]. FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer.
- Rosa K. OncLive. 2023 [cited 2023 Nov 30]. FDA approves first radiohybrid PSMA-targeted PET imaging agent for prostate cancer.
- Appropriate use criteria for prostate-Specific Membrane Antigen (PSMA) PET imaging [Internet]. [cited 2023 Dec 18].
- Kuten J, Dekalo S, Mintz I, Yossepowitch O, Mano R, Even-Sapir E. The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0. EJNMMI Res. 2021 Jan 6;11(1):3.
- Chapter 10: Analysing data and undertaking meta-analyses [Internet]. [cited 2023 Dec 1].
- Maisto C, Aurilio M, Morisco A, de Marino R, Buonanno Recchimuzzo MJ, Carideo L, et al. Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer. Molecules [Internet]. 2022 Jun 16;27(12).