Initial Clinical Experience with 90 Y-FAPI-46 Radioligand Therapy for Advanced-Stage Solid Tumors: A Case Series of 9 Patients

The Journal of Nuclear Medicine

article

Wolfgang P. Fendler¹  Rainer Hamacher²  Justin Ferdinandus¹  Pedro Fragoso Costa¹  Lukas Kessler¹  Manuel Weber¹  Nader Hirmas¹  Karina Kostbade²  Sebastian Bauer²  Martin Schuler²  Marit Ahrens³  Hans-Ulrich Schildhaus²  Christoph Rischpler¹  Hong Grafe¹  Jens T. Siveke⁴  Ken Herrmann¹ 

[1] Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen;German Cancer Consortium ,(DKTK), Partner Site University Hospital Essen, and German Cancer Research Center;Medical Clinic II, University Hospital Frankfurt;Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg–Essen;Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Medicine Essen;Division of Solid Tumor Translational Oncology, German Cancer Consortium ,(DKTK, Partner Site Essen) and German Cancer Research Center

关键词: FAPI;    theranostics;    fibroblast activation protein;    solid tumors;   

DOI  :  10.2967/jnumed.121.262468

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 of the feasibility and safety of 90Y-FAPI-46 for radioligand therapy of extensively pretreated patients with solid tumors. Methods: Patients were considered for 90Y-FAPI-46 therapy if they showed both an exhaustion of all approved therapies based on multidisciplinary tumor board decision, and high FAP expression, defined as SUVmax greater than or equal to 10 in more than 50% of all lesions. If tolerated, 90Y-FAPI-46 bremsstrahlung scintigraphy was performed after therapy to confirm systemic distribution and focal tumor uptake, and 90Y-FAPI-46 PET scans were performed at multiple time points to determine absorbed dose. Blood-based dosimetry was used to determine bone marrow absorbed dose. Adverse events were graded using Common Terminology Criteria for Adverse Events (version 5.0). Results: Nine patients either with metastatic soft-tissue or bone sarcoma (n = 6) or with pancreatic cancer (n = 3) were treated between June 2020 and March 2021. Patients received a median of 3.8 GBq (interquartile range [IQR], 3.25–5.40 GBq) for the first cycle, and 3 patients received subsequent cycles with a median of 7.4 GBq (IQR, 7.3–7.5 GBq). Posttreatment 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 Gy/GBq) in the kidney, 0.04 Gy/GBq (IQR, 0.03–0.06 Gy/GBq) in bone marrow, and less than 0.26 Gy/GBq in the lung and liver. Measured tumor lesions received up to 2.28 Gy/GBq (median, 1.28 Gy/GBq). New laboratory G3 or G4 toxicities were noted in 4 patients (44%, n = 2 patients with thrombocytopenia only, n = 2 patients with new onset of thrombocytopenia and anemia). Other G3 or G4 laboratory-based adverse events occurred in 2 patients or fewer. No acute toxicities attributed to 90Y-FAPI-46 were noted. Radiographic disease control was noted in 4 patients (50%). Conclusion: FAP-targeted radioligand therapy with 90Y-FAPI-46 was well tolerated, with a low rate of attributable adverse events. Low radiation doses to at-risk organs suggest feasibility of repeat cycles of 90Y-FAPI-46. We observed signs of tumor response, but further studies are warranted to determine efficacy and the toxicity profile in a larger cohort.

【 授权许可】

CC BY