Fibroblast activation protein (FAP) is highly expressed in many cancers, especially sarcomas, and represents a promising theranostic target. We present an updated retrospective analysis of 90Y-FAP inhibitor (FAPI)-46 treatment in patients with sarcoma or other solid tumors. Methods: We performed monocentric analysis of patients with progressive sarcoma or metastatic cancer who were eligible for 90Y-FAPI-46 therapy after approved treatments had been exhausted and who showed high FAP expression (SUVmax, ≥10 in over 50% of lesions on 68Ga-FAPI-46 PET). After therapy, 90Y-FAPI-46 scintigraphy confirmed distribution and uptake, and serial 90Y-FAPI-46 PET/CT scans measured absorbed doses. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. Tumor responses were evaluated using RECIST and PERCIST. Results: Thirty patients-23 (77%) with sarcoma, 3 (10%) with pancreatic cancer, 1 (3%) with prostate cancer, 1 (3%) with gastric cancer, 1 (3%) with nonmelanoma skin cancer, and 1 (3%) with cholangiocarcinoma-received a total of 77 cycles of 90Y-FAPI-46 radiopharmaceutical therapy between June 2020 and December 2023 and were followed until death or the last follow-up (April 2024). The median interval between cycles was 5 mo (interquartile range [IQR], 4 mo). Of the 30 patients, 11 (37%) received 4 or more cycles. A median of 3.7 GBq (IQR, 3.7-3.8 GBq) was administered during the first cycle, and a median of 7.4 GBq (IQR, 7.2-7.4 GBq) was administered for subsequent cycles. The mean absorbed dose was 0.48 Gy/GBq (SD, 0.06 Gy/GBq) in the kidneys and 0.04 Gy/GBq (SD, 0.01 Gy/GBq) in the bone marrow. Lesions with the highest uptake absorbed a mean dose of 2.4 Gy/GBq (SD, 1.04 Gy/GBq). After treatment, hematotoxicity of any grade was observed in 20 of 30 (67%) patients. Eight of 30 (27%) patients reached a Common Terminology Criteria for Adverse Events grade of at least 3, experiencing adverse events that included thrombocytopenia in 2 (6%), neutropenia in 2 (6%), anemia in 2 (6%), leukopenia in 1 (3%), and elevated γ-glutamyl transferase in 1 (3%) patient. RECIST (n = 25) and PERCIST (n = 20) responses after treatment were assessed. Disease control according to RECIST was 48% (12/25), including 3 partial responses (12%). Disease control correlated with extended overall survival (median, 14.6 vs. 1.9 mo). Metabolic response per PERCIST was observed in 12 of 20 (60%) patients. Conclusion: With long-term follow-up, the favorable safety profile of 90Y-FAPI-46 therapy is confirmed. Nearly half of the patients demonstrated disease stabilization, almost exclusively in sarcomas. Our findings support the role of FAP-directed radiopharmaceutical therapy in patients with metastatic sarcoma.

Solitary fibrous tumor (SFT) is a rare soft-tissue sarcoma with limited treatment options, especially in advanced or metastatic cases. Fibroblast activation protein α (FAPα) is overexpressed in certain sarcomas, including SFTs, making it a promising target for diagnostics and radiopharmaceutical therapy (RPT). We present the cases of 3 patients with metastatic SFTs who, after exhausting standard treatments, underwent molecular profiling and showed elevated FAPα expression. Methods: Messenger RNA and protein expression of FAPα were examined in biopsy samples from 3 patients participating in the Molecularly Aided Stratification for Tumor Eradication Research program, a multicenter observational study focused on biology-driven stratification of adults with advanced cancer. Messenger RNA expression levels were quantified as transcripts per million, with RNA extraction, sequencing, and data processing performed using established protocols. Protein expression was assessed and stained with FAPα immunohistochemistry using a recombinant anti-FAPα antibody. Following the recommendation of the molecular tumor board, these patients received 90Y-labeled fibroblast activation protein inhibitor (FAPI)-46 RPT because of the high uptake observed in 68Ga-FAPI-46 PET/CT scans. Results: 90Y-FAPI-46 RPT led to substantial clinical benefits, including metabolic resolution and symptom relief, with disease control confirmed using RECIST and PERCIST. Treatment was well-tolerated, with only minor adverse events observed. Conclusion: Our findings underscore the utility of FAPα screening as a predictive biomarker and the potential of FAP-targeted RPT as a viable treatment for advanced SFT.

Ziel/Aim: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are a rare disease [1] [2]. Current guidelines recommend treatment with somatostatin receptor (SSTR) targeting radioligand therapy (RLT) [1] [3]. SSTR-RLT is available as 177Lu-radiolabeled somatostatin analogues locally compounded by hospitals (non-licensed product) and as EMA approved product with standardized formulation and application. Limited real-world data exist on the German care situation with SSTR-RLT.

Patients with bulky neuroendocrine liver metastases (NELM) undergoing PRRT with [ 177 Lu]Lu‐DOTATATE have a worse survival than patients with limited liver metastases. Previously, the safety and efficacy of additional selective internal radiotherapy (SIRT), using holmium‐166 ( 166 Ho)‐microspheres, directly following PRRT in patients with NELM were confirmed in the prospective HEPAR PLuS study. The aim of the current study was to provide insight into the efficacy and survival benefit of PRRT + 166 Ho‐SIRT over PRRT‐only by means of a propensity score matched historical cohort. A multicenter retrospective data collection was performed to match patients treated with PRRT‐only to the prospectively collected HEPAR PLuS study patients. Demographic, clinical, laboratory, and imaging data were collected. The primary endpoint was the proportion of patients with progression‐free survival (PFS) at 2 years after the start of PRRT. Secondary endpoints included the proportion of patients with 2‐year hepatic PFS (hPFS), general PFS and hPFS, objective response rates (ORR), and overall survival (OS). Twenty‐four patients were 1:1 matched and included in the analysis. All key matching criteria were balanced between cohorts if feasible. The proportion of patients with PFS and hPFS at 2 years was 68% and 82% after PRRT + 166 Ho‐SIRT versus 55% and 50% after PRRT only. Time to median PFS was comparable (31 vs. 30 months). An initial delay in hepatic progression or death of any cause was observed in PRRT + 166 Ho‐SIRT mNET patients (75% probability of PFS at 27 vs. 22 months), most notably in intestinal tumors (75% probability of PFS at 26 vs. 15 months). Best ORR was 71% after PRRT + 166 Ho‐SIRT versus 25% after PRRT only. This study showed that 166 Ho‐SIRT after PRRT (vs. PRRT‐only) had a positive effect on the liver disease progression in patients with NELM, increasing the 2‐year hPFS rate and tumor response and delaying hepatic progression or death. However, this effect did not translate into improving general PFS and OS.

Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is an approved treatment for metastatic neuroendocrine tumors (NETs). Although the therapy is effective, hematologic toxicity, particularly leukopenia, remains a significant concern. The spleen, which accumulates radiolabeled somatostatin analogs, may play a critical role in modulating this toxicity. This study investigates whether patients undergoing PRRT after splenectomy exhibit lower hematologic toxicity. Methods: This multicenter retrospective study included 68 patients with metastatic NETs treated with PRRT between 2009 and 2022. Splenectomized patients (n = 34) were matched to nonsplenectomized patients on the basis of age, sex, tumor location, grading, metastatic pattern, and treatment cycles. Hematologic parameters (leukocytes, lymphocytes, neutrophils, hemoglobin, and platelets) were assessed at baseline and 12 and 24 mo after PRRT. Hematotoxicity was graded using Common Terminology Criteria for Adverse Events. Statistical analyses included t test, Mann-Whitney U test, and Fisher exact test, with an α of 0.05 and Bonferroni adjustment applied. Results: Splenectomized patients had significantly lower rates of leukopenia, with a mean decline of 12.8% in leukocyte count at 24 mo versus 47.2% in nonsplenectomized patients (P < 0.001), and a higher median absolute leukocyte count (7.2 vs. 4.2 × 10³/mm³, P < 0.001). Leukopenia occurred in 2 splenectomized patients compared with 20 in the control group (P < 0.001). Lymphocyte decline was also less pronounced, with higher absolute counts at 24 mo. Platelet counts were consistently higher postsplenectomy, although relative changes over time were not significant. Neutrophil counts and hemoglobin levels remained comparable between groups. Conclusion: Splenectomy appears to reduce leukopenia and improve hematologic tolerability in NET patients undergoing PRRT, highlighting the spleen's role in leukocyte regulation. These patients may better tolerate intensified PRRT regimens, including additional cycles or reinduction, with minimal toxicity. This is particularly relevant for patients with pancreatic NETs, who frequently undergo splenectomy and face a poorer prognosis. Prospective studies are needed to further clarify the spleen's impact on PRRT-related hematotoxicity and guide treatment optimization.

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP14)1 May 2024MP14-18 ONCOLOGICAL OUTCOMES OF PN1 PROSTATE CANCER PATIENTS TREATED WITH RADICAL PROSTATECTOMY: DOES MOLECULAR IMAGING HAVE A PROGNOSTIC IMPACT? RESULTS OF A LARGE, MULTI-INSTITUTIONAL SERIES Francesco Barletta, Giorgio Gandaglia, Pawel Rajwa, Juan Gomez Rivas, Luca Afferi, Claudia Kesch, Christopher Darr, Junlong Zhuang, Fabio Zattoni, Helena Lanzafame, Giancarlo Marra, Nicolai Huebner, Steven Joniau, Eugenio Brunocilla, Agostino Mattei, Cristian Fiori, Cabrera Maria, Enrico Checcucci, Maria Picchio, Arturo Chiti, Roderick van den Bergh, Shahrok Shariat, Francesco Montorsi, and Alberto Briganti Francesco BarlettaFrancesco Barletta , Giorgio GandagliaGiorgio Gandaglia , Pawel RajwaPawel Rajwa , Juan Gomez RivasJuan Gomez Rivas , Luca AfferiLuca Afferi , Claudia KeschClaudia Kesch , Christopher DarrChristopher Darr , Junlong ZhuangJunlong Zhuang , Fabio ZattoniFabio Zattoni , Helena LanzafameHelena Lanzafame , Giancarlo MarraGiancarlo Marra , Nicolai HuebnerNicolai Huebner , Steven JoniauSteven Joniau , Eugenio BrunocillaEugenio Brunocilla , Agostino MatteiAgostino Mattei , Cristian FioriCristian Fiori , Cabrera MariaCabrera Maria , Enrico CheccucciEnrico Checcucci , Maria PicchioMaria Picchio , Arturo ChitiArturo Chiti , Roderick van den BerghRoderick van den Bergh , Shahrok ShariatShahrok Shariat , Francesco MontorsiFrancesco Montorsi , and Alberto BrigantiAlberto Briganti View All Author Informationhttps://doi.org/10.1097/01.JU.0001009428.69695.82.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nodal metastases (pN1) represent a predictor of adverse cancer control outcomes in prostate cancer (PCa) patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). Among pN1 patients, cN status has not been shown to impact on cancer control in the conventional imaging era. However, it is unclear whether these findings are applicable to patients staged with PSMA. We tested whether the presence of PSMA-PET nodal lesions (miN1) and their number have a prognostic impact in pN1 patients. METHODS: Overall, we retrieved 106 pN1 PCa patients with preoperative PSMA-PET treated with RP+ePLND without neoadjuvant therapies at 9 referral centres between 2016-2023. Study outcome was biochemical failure (BCF) after RP defined as a PSA value≥0.1 ng/ml at 6-week or two consecutive PSA values ≥0.2 ng/ml. Kaplan-Meier (KM) plots depicted BCF-free survival. Multivariable Cox-regression (MCR) models were fitted to test for the impact of miN1 stage and nodal burden at PSMA-PET (0 vs ≥1; 0 vs 1 vs ≥2) on BCF. In MCR models covariates consisted of: PSA at diagnosis, biopsy grade group (GG; 1-3 vs 4 vs 5), and MRI stage (organ-confined vs extracapsular-extension vs seminal vesicles invasion). Accuracy of MCR models without (model 1) vs including PET-PSMA information (model 2) vs stratifying PSMA-PET results according to number of nodal lesions (0 vs 1 vs ≥2, model 3) were assessed with models derived C-index. RESULTS: Median age and PSA at diagnosis were 67 (62-71) and 10 (7-22) ng/ml. A total of 50 (47%) patients had miN1 disease, with 21 (42%) vs 29 (58%) of these exhibiting 1 vs ≥2 lesions. The 2-yr BCF-free rates were 48% for miN0 vs 29% for miN1 patients. In MCR models miN1 stage (HR: 2.6, 95% CI 1.4-4.9, p=0.003) achieved independent predictor status for higher BCF risk. When stratifying patients according to the number (0 vs 1 vs ≥2) of suspicious nodal lesions at PSMA-PET, only the presence of ≥2 nodal lesions achieved independent predictor status for BCF (HR: 5.4, 95% CI 2.4-12.2, p<0.001). MCR models derived C-index were respectively 68 (model 1) vs 77 (model 2) vs 84% (model 3). CONCLUSIONS: In pN1 patients, the presence of visible nodal lesions at PSMA-PET is associated with BCF after RP+ePLND. Inclusion of information on PSMA-PET nodal burden increased the accuracy of MCR models predicting BCF. Presence of multiple PSMA-PET uptakes in the pelvis, but not a single positive spot, was associated with adverse cancer control and might prompt the use of early intensification approaches. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e227 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Francesco Barletta More articles by this author Giorgio Gandaglia More articles by this author Pawel Rajwa More articles by this author Juan Gomez Rivas More articles by this author Luca Afferi More articles by this author Claudia Kesch More articles by this author Christopher Darr More articles by this author Junlong Zhuang More articles by this author Fabio Zattoni More articles by this author Helena Lanzafame More articles by this author Giancarlo Marra More articles by this author Nicolai Huebner More articles by this author Steven Joniau More articles by this author Eugenio Brunocilla More articles by this author Agostino Mattei More articles by this author Cristian Fiori More articles by this author Cabrera Maria More articles by this author Enrico Checcucci More articles by this author Maria Picchio More articles by this author Arturo Chiti More articles by this author Roderick van den Bergh More articles by this author Shahrok Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

291 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior diagnostic accuracy for detecting regional and distant metastases compared to conventional imaging (CT, bone scan, and MRI) in men with prostate cancer. This has the potential to guide definitive radiation therapy (dRT) patient selection and planning. Whether the use of improved diagnostic accuracy imaging improves patient outcomes remains to be demonstrated in clinical trials. Methods: This multi-institutional phase III randomized clinical trial (PSMA-dRT, NCT04457245) was designed to randomize 312 men with unfavorable intermediate-risk or high-risk prostate cancer 1.08:1 between receiving (n=162) and not receiving (n=150) a PSMA PET/CT prior to starting dRT. Treating radiation oncologists incorporated the PSMA PET/CT into radiotherapy planning. All other imaging modalities were allowed in the control arm. There were no prespecified androgen deprivation therapy (ADT) or dRT dose and volumes protocols. The primary endpoint was 5-year progression-free survival (PFS). Results: 54 patients were randomized between November 2020 and December 2021 (25 to PSMA PET/CT and 29 to control). The trial closed early following FDA approval and insurance coverage of PSMA PET/CT, since treatment without PSMA PET/CT in the control group was no longer acceptable for many patients and physicians. Among patients staged with PSMA PET/CT in the intervention group, 14 patients (58.3%) had localized miT2b-cN0M0 disease, 6 (25.0%) had locally advanced disease (miT3a-bN0M0), 3 (12.5%) had regional disease (miN1M0), and 1 (4.2%) had nodal and distant disease (miN1M1b). Four patients (16.7%) were upstaged relative to their staging at time of randomization. All three patients with miN1M0 disease received pelvic lymph node irradiation as part of their dRT course. The patient with miN1M1b disease received upfront ADT with abiraterone acetate and prednisone followed by consolidative radiotherapy to the prostate and pelvic lymph nodes. With a median follow-up of 21 months (interquartile range: 17.6-26.3 months), there were no cases of biochemical failure (PSA >2 ng/mL above nadir), radiographic or biopsy-proven recurrence, salvage therapy, or prostate cancer death in either arm. Two-year PFS was 93.8% in the PSMA PET/CT arm (due to 2 non prostate cancer deaths) and 100% in the control arm. There was no significant difference in PFS between the PSMA PET/CT and control arms ( P=0.13). Conclusions: PSMA PET/CT upstaged 17% of patients compared to prior baseline staging, which allowed for more accurate treatment planning. Due to early termination, this trial was underpowered to assess the effect of PSMA PET/CT on PFS. PSMA-dRT is currently under submission for complete enrollment and data pooling at German sites. Clinical trial information: NCT04457245 .

5016 Background: Prostate Specific Membrane Antigen Positron-Emission-Tomography (PSMA-PET) was introduced for prostate cancer staging in 2012. PSMA-PET reported by standardized PROMISE criteria delivers accurate staging with potential prognostic value. Here we assess the prognostic value of PSMA-PET including tumor volume in a large prostate cancer dataset with overall survival follow-up and compare it head-to-head to clinical risk scores. Methods: Prostate cancer patients, who underwent PSMA-PET between October 2014 and December 2019 at the Essen University Hospital, were analyzed retrospectively. We collected PSMA-PET stage using the molecular imaging TNM system (miTNM), tumor volume, SUVmean and overall survival follow-up. The dataset was split into development and validation cohorts (2:1). We created a visual and quantitative nomogram based on Cox regression models with LASSO penalty using the development cohort. Performance of nomograms in the validation cohort were measured using C-index and calibration plots. Head-to-head comparison to clinical risk scores for each staging group was examined using ROC-curves and C-index. Results: The cohort includes 1612 prostate cancer patients across all disease stages with 567 (35.2%) recorded deaths. PSMA-PET based predictors included into the quantitative PSMA-PET nomogram were locoregional lymph node metastases (miN2), distant metastases (miM1a, miM1b pattern, miM1c), tumor volume and tumor SUVmean (Table). The visual nomogram includes distant metastases and total tumor lesion count. Overall C-indices were 0.81 or 0.78 for the quantitative or visual nomogram, respectively. The quantitative PSMA-PET nomogram was superior to STARCAP at initial staging (AUC: 0.72 vs. 0.53; p=0.02), to EAU risk score at BCR (AUC: 0.69 vs. 0.52; p<0.001), and to NCCN groups at any timepoint (AUC: 0.81 vs. 0.73; p<0.001). The visual PSMA-PET nomogram was superior to EAU risk score (AUC: 0.64 vs. 0.52; p<0.001) and NCCN groups (AUC: 0.79 vs. 0.73 p<0.001). Conclusions: Our prognostic PSMA-PET nomograms based on PROMISE criteria were accurate in early and late stages of prostate cancer. Prediction of overall survival was superior when compared to clinical risk tools. Multi-center validation in the PROMISE registry is ongoing. Development cohort (n=1110 patients) univariate regression findings for PROMISE variables included in the quantitative PSMA-PET nomogram for prediction of overall survival.[Table: see text]

To assess the diagnostic accuracy of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68Ga-FAPI and 18F-FDG PET and had adequate lesion validation for accuracy analysis. Each scan was evaluated for the detection of primary tumor, lymph nodes, and visceral and bone metastases. True or false positivity and negativity to detected lesions was assigned on the basis of histopathology from biopsies or surgical excision, as well as imaging validation. Results:68Ga-FAPI PET revealed higher accuracy than 18F-FDG PET in the detection of colorectal cancer (n = 14; per-patient, 85.7% vs. 78.6%; per-region, 95.6% vs. 91.1%) and prostate cancer (n = 22; per-patient, 100% vs. 90.9%; per-region, 96.4% vs. 92.7%). 68Ga-FAPI PET and 18F-FDG PET had comparable per-patient accuracy in detecting breast cancer (n = 16, 100% for both) and head and neck cancers (n = 10, 90% for both modalities). 68Ga-FAPI PET had lower per-patient accuracy than 18F-FDG PET in cancers of the bladder (n = 12, 75% vs. 100%) and kidney (n = 10, 80% vs. 90%), as well as lymphoma (n = 9, 88.9% vs. 100%) and myeloma (n = 10, 80% vs. 90%). Conclusion:68Ga-FAPI PET demonstrated higher diagnostic accuracy than 18F-FDG PET in the diagnosis of colorectal cancer and prostate cancer, as well as comparable diagnostic performance for cancers of the breast and head and neck. Accuracy and impact on management will be further assessed in an ongoing prospective interventional trial (NCT05160051).

To assess the diagnostic accuracy of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68Ga-FAPI and 18F-FDG PET and had adequate lesion validation for accuracy analysis. Each scan was evaluated for the detection of primary tumor, lymph nodes, and visceral and bone metastases. True or false positivity and negativity to detected lesions was assigned on the basis of histopathology from biopsies or surgical excision, as well as imaging validation. Results: 68Ga-FAPI PET revealed higher accuracy than 18F-FDG PET in the detection of colorectal cancer (n = 14; per-patient, 85.7% vs. 78.6%; per-region, 95.6% vs. 91.1%) and prostate cancer (n = 22; per-patient, 100% vs. 90.9%; per-region, 96.4% vs. 92.7%). 68Ga-FAPI PET and 18F-FDG PET had comparable per-patient accuracy in detecting breast cancer (n = 16, 100% for both) and head and neck cancers (n = 10, 90% for both modalities). 68Ga-FAPI PET had lower per-patient accuracy than 18F-FDG PET in cancers of the bladder (n = 12, 75% vs. 100%) and kidney (n = 10, 80% vs. 90%), as well as lymphoma (n = 9, 88.9% vs. 100%) and myeloma (n = 10, 80% vs. 90%). Conclusion: 68Ga-FAPI PET demonstrated higher diagnostic accuracy than 18F-FDG PET in the diagnosis of colorectal cancer and prostate cancer, as well as comparable diagnostic performance for cancers of the breast and head and neck. Accuracy and impact on management will be further assessed in an ongoing prospective interventional trial (NCT05160051).

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of 68Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of 68Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent 68Ga-FAPI PET/CT and 18F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUVmax) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of 68Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of 68Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUVmax greater than 10 for all tumor regions. Results: 68Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUVmax ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of 68Ga-FAPI versus 18F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of 68Ga-FAPI was higher than that of 18F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). 68Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, 68Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18F-FDG PET. 68Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.