Initial clinical experience with ⁹⁰Y-FAPI-46 radioligand therapy for advanced stage solid tumors: a case series of nine patients

Abstract

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 ( 68 Ga-FAPI-46) for PET imaging. Here, we report our initial experience in terms of feasibility and safety of 90 Y-labelled FAPI-46 ( 90 Y-FAPI-46) for radioligand therapy (RLT) of extensively pretreated patients with solid tumors. Methods: Patients were considered for 90 Y-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, posttherapeutic 90 Y-FAPI-46 bremsstrahlung scintigraphy was performed to visually confirm systemic distribution and focal tumor uptake, and 90 Y-FAPI-46 PET scans at multiple timepoints 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 90 Y-FAPI-46 bremsstrahlung scintigraphy demonstrated sufficient 90 Y-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 1.28Gy/GBq). Hematologic G3/G4 toxicities were noted in four patients (44%), of which

Multimodal Imaging-Based Potential Visualization of the Tumor Microenvironment in Bone Metastasis

“…Sodium-iodide symporter (NIS) expressed on the cell membrane is an important tool for the diagnosis ( 123 I) and therapy ( 131 I) of DTC. NIS expression in tumor cells is maintained in the early phase of distant metastasis, where 131 I therapy contributes to patient outcomes [93]. However, when the degree of differentiation is poor, the expression level of NIS and iodine uptake decreases.…”

“…Conversely, glucose metabolism, which is visualized as FDG uptake on 18 F-FDG PET/CT, increases (Figure 3) [94]. This flip-flop phenomenon is important for further management plans for patients with distant metastasis, including BM, as 131 I therapy is highly limited in DTC patients with poor differentiation. (E-H) A 66-year-old female patient with PTC.…”

“…(E-H) A 66-year-old female patient with PTC. 131 I whole-body scan (E) and SPECT/CT (F) show multiple iodine uptake in metastatic bone lesions, including those in the T1 vertebra (arrowhead). However, 18 F-FDG PET/CT (G,H) shows no significant uptake at the same site.…”

“…Different tracer avidities in bone metastases from papillary thyroid carcinoma (PTC) according to differentiation status. (A-D) A 79-year-old male patient with PTC 131. I whole-body scan (A) and single-photon emission computed tomography (SPECT)/computed tomography (CT) (B) show little iodine uptake in metastatic lesions located in the sternum (arrow).…”

“…In contrast,18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT (C,D) shows intense FDG uptake in the sternum (arrow). (E-H) A 66-year-old female patient with PTC 131. I whole-body scan (E) and SPECT/CT (F) show multiple iodine uptake in metastatic bone lesions, including those in the T1 vertebra (arrowhead).…”