Journal Article

FZJ-2025-01118

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy

Heilinger, J. ; Roth, K. S. ; Weis, H. ; Fink, A. ; Weindler, J. ; Dietlein, F. ; Krapf, P.FZJ* ; Schomäcker, K. ; Neumaier, B.FZJ* ; Dietlein, M. ; Drzezga, A.FZJ* ; Kobe, C. (Corresponding author)Extern*

2025
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1186/s13550-024-01190-7  doi:10.34734/FZJ-2025-01118

Abstract: Background In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinctbiodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directedradioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In thisstudy, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid glandand spleen as well as the respective tumor-to-background ratios (TBR) of different 18F-labeled PSMA ligands to today’sstandard radiopharmaceutical 68Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancerwho underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.Results Differences in background activity among different PSMA-PET tracers lead to variations in tumor-tobackgroundratios (TBR). In [18F]F-DCFPyL-PET, TBR with the liver as the reference organ (TBRliver) was comparableto [68Ga]Ga-PSMA-11-PET, while [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET showed significantly lower values.Using the parotid gland as the reference (TBRparotidgland), [18F]F-DCFPyL-PET exhibited significantly higher values,whereas [18F]F-PSMA-1007-PET and [18F]F-JK-PSMA-7-PET were comparable. For the spleen (TBRspleen), [18F]F-JK-PSMA-7-PET was comparable, but [18F]F-DCFPyL-PET and [18F]F-PSMA-1007-PET showed significantly higher and lowervalues, respectively. An additional Bland-Altman analyses revealed low bias for [18F]F-DCFPyL-PET in TBRparotidgland,whereas significant differences in TBRliver and TBRspleen for the other tracers resulted in higher bias.Conclusion Different PSMA-PET tracers exhibit distinct biodistribution patterns, leading to variations in tumor-tobackgroundratios (TBR) in reference organs such as the liver, parotid gland, and spleen. Patient selection for PSMA-directed radioligand therapy is currently based on a semiquantitative approach using the liver as a reference regionin [68Ga]Ga-PSMA-11-PET. Thus, the use of alternative [18F]-labeled tracers may result in under- or overestimation of apatient’s suitability for therapy. This highlights the importance of a comprehensive understanding of the differencesin tracer-specific uptake behavior for accurate decisions regarding PSMA-expression levels. However, as the patientcohort in this study is at earlier disease stages, the generalizability of these findings to later-stage patients remainsunclear and requires further investigation.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)
2. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2025

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