RT Journal Article SR Electronic T1 Initial clinical experience with 90Y-FAPI-46 radioligand therapy for advanced stage solid tumors: a case series of nine patients JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.121.262468 DO 10.2967/jnumed.121.262468 A1 Ferdinandus, Justin A1 Fragoso Costa, Pedro A1 Kessler, Lukas A1 Weber, Manuel A1 Hirmas, Nader A1 Kostbade, Karina A1 Bauer, Sebastian A1 Schuler, Martin A1 Ahrens, Marit A1 Schildhaus, Hans-Ulrich A1 Rischpler, Christoph A1 Grafe, Hong A1 Siveke, Jens T A1 Herrmann, Ken A1 Fendler, Wolfgang A1 Hamacher, Rainer YR 2021 UL http://jnm.snmjournals.org/content/early/2021/08/12/jnumed.121.262468.abstract AB Introduction: Fibroblast activation protein (FAP) is overexpressed in several solid tumors and therefore represents an attractive target for radiotheranostic applications. Recent investigations demonstrated rapid and high uptake of small-molecule inhibitors of FAP (68Ga-FAPI-46) for PET imaging. Here, we report our initial experience in terms of feasibility and safety of 90Y-labelled FAPI-46 (90Y-FAPI-46) for radioligand therapy (RLT) of extensively pretreated patients with solid tumors. Methods: Patients were considered for 90Y-FAPI-46 therapy in case of (a) exhaustion of all approved therapies based on multidisciplinary tumor board decision and (b) high FAP expression, defined as SUVmax ≥ 10 in more than 50% of all lesions. If tolerated, post-therapeutic 90Y-FAPI-46 bremsstrahlung scintigraphy was performed to visually confirm systemic distribution and focal tumor uptake, and 90Y-FAPI-46 PET scans at multiple time-points were performed to determine absorbed dose. Blood-based dosimetry was used to determine bone-marrow absorbed dose. Adverse Events were graded using CTCAE v.5.0. Results: Nine patients with either metastatic soft tissue or bone sarcoma (N = 6) and pancreatic cancer (N = 3) were treated between June 2020 and March 2021. Patients received a median of 3.8 (IQR 3.25-5.40) GBq for the first cycle and three patients received subsequent cycles with a median of 7.4 (IQR 7.3-7-5) GBq. Post-therapy 90Y-FAPI-46 bremsstrahlung scintigraphy demonstrated sufficient 90Y-FAPI-46 uptake in tumor lesions in 7 of 9 patients (78%). Mean absorbed dose was 0.52 Gy/GBq (IQR 0.41-0.65) in kidney, 0.04 Gy/GBq (IQR 0.03-0.06) in bone marrow and below 0.26 Gy/GBq in the lung and liver. Measured tumor lesions received up to 2.28 Gy/GBq (median 1.28 Gy/GBq). Hematologic G3/G4 toxicities were noted in four patients (44%), of which thrombocytopenia was most prevalent (N = 6; 67%), whereas other G3/G4 laboratory-based adverse events were N ≤ 2. No acute toxicities attributed to 90Y-FAPI-46 were noted. Radiographic disease control was noted in three patients (33 %). Conclusion: FAP-targeted RLT with 90Y-FAPI-46 was well tolerated with a low rate of attributable adverse events. Low radiation doses to organs at risk suggest feasibility of repeat cycles of 90Y-FAPI-46. We observe signs of clinical activity, but further studies are warranted to determine efficacy and toxicity profile in a larger cohort.