%0 Journal Article %A Heilinger, Jan %A Roth, Katrin Sabine %A Weis, Henning %A Fink, Antonis %A Weindler, Jasmin %A Dietlein, Felix %A Krapf, Philipp %A Schomäcker, Klaus %A Neumaier, Bernd %A Dietlein, Markus %A Drzezga, Alexander %A Kobe, Carsten %T 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 %J EJNMMI Research %V 15 %N 1 %@ 2191-219X %C Heidelberg %I Springer %M FZJ-2025-01118 %P 4 %D 2025 %X 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. %F PUB:(DE-HGF)16 %9 Journal Article %$ 39792324 %U <Go to ISI:>//WOS:001394361800001 %R 10.1186/s13550-024-01190-7 %U https://juser.fz-juelich.de/record/1038069