[en] To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [${}^{68}$Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC). Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [${}^{68}$Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed. The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [${}^{68}$Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC. Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.

[en] Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. In 81 patients receiving either one of the following molecular imaging probes, [${}^{68}$Ga]Ga-FAPI, [${}^{68}$Ga]Ga-PSMA, or [${}^{68}$Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. We found a negative correlation between GFR and [${}^{68}$Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [${}^{68}$Ga]Ga-DOTATOC and [${}^{68}$Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [${}^{68}$Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. There is a significant negative correlation between renal parenchymal [${}^{68}$Ga]Ga-FAPI uptake and GFR, which was not the case for [${}^{68}$Ga]Ga-DOTATOC and [${}^{68}$Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [${}^{68}$Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis.

[en] ${}^{68}$Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer ${}^{18}$F-FDG was performed in selected cases. A total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent ${}^{68}$Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional ${}^{18}$F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group. In 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in ${}^{68}$Ga-FAPI compared to ${}^{18}$F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of ${}^{68}$Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to ${}^{18}$F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed. Due to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than ${}^{18}$F-FDG-PET/CT, ${}^{68}$Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.

[en] FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of ${}^{68}$Ga-FAPI versus standard-of-care ${}^{18}$F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both ${}^{68}$Ga-FAPI and ${}^{18}$F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. ${}^{68}$Ga-FAPI uptake in primary tumors and metastases was comparable to ${}^{18}$F-FDG in most cases. The SUVmax was significantly lower for ${}^{68}$Ga-FAPI than ${}^{18}$F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, ${}^{68}$Ga-FAPI TBRs were significantly higher than ${}^{18}$F-FDG TBRs in some sites, including liver and bone metastases. Quantitative tumor uptake is comparable between ${}^{68}$Ga-FAPI and ${}^{18}$F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for ${}^{68}$Ga-FAPI. Thus, ${}^{68}$Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological ${}^{18}$F-FDG uptake.