Thomas Hope, MD, Associate Professor in Residence at UC San Francisco. In this video, he speaks about the ASCO 2022 Abstract – Imaging of solid tumors using 68Ga-FAP-2286.
Origins:
Fibroblast Activation Protein (FAP) is a transmembrane protein that is overexpressed on cancer-associated fibroblasts (CAFs) and is prevalent in many epithelial malignancies, implying that FAP is an appealing imaging and therapeutic target. FAP-2286 is a cyclic peptide that binds to FAP and is being tested as a radioligand therapy for patients with FAP-positive solid tumors. It is uncertain what role 68Ga-FAP-2286 plays as a diagnostic agent. We offer an interim investigation of 68Ga-ability FAP-2286’s to detect metastatic disease across several cancer types.
Methodology:
This is a first-in-human Phase I/II study using 68Ga-FAP-2286 (NCT04621435), with a total enrollment of 65 patients divided into three cohorts: dosimetry (n = 5), RECIST detectable disease (n = 30), and metastases at risk (n = 30). 27 points had been enrolled by the cutoff date of February 12, 2022. (3 in cohort 1, 15 in cohort 2 and 9 in cohort 3). The five largest lesions from each patient were included in the analysis, and the maximum standardized uptake value (SUVmax) of the 68Ga-FAP-2286 as well as the size (short axis for lymph nodes) were recorded for each lesion. The uptake on the two scans was compared in patients who had an accessible FDG PET performed within 8 weeks after the 68Ga-FAP-2286 PET.
Outcomes:
Nine patients had bladder cancer, five had sarcoma, four had head and neck squamous cell cancer (HNSCCA), three had breast cancer (BC), and three had castration resistant prostate cancer (CRPC) (CRPC). The majority of patients (89 percent, 24/27) had tumors that were positive for uptake on 68Ga-FAP-2286 PET, with 30 lesions measuring 1.5 cm and 17 measuring less than 1.0 cm. A paired FDG PET was performed on 16 subjects. The average SUVmax on 68Ga-FAP-2286 PET was 244 percent higher than on FDG PET in these patients. Only two points demonstrated higher FDG PET uptake than 68Ga-FAP-2286 PET uptake (HNSCCA and DSRCT). The greatest relative uptake was observed in two BC patients (both 3.4 times higher on 68Ga-FAP-2286 PET); the average SUVmax in BC was 16.6. CRPC had the lowest uptake on 68Ga-FAP-2286 PET, with an average SUVmax of 7.0. Sarcoma had uneven uptake, with one point having an SUVmax of 4.5 (Ewing’s) and two points having an SUVmax of more than 30. (both undifferentiated pleomorphic). Although sarcoma exhibited a significant 68Ga-FAP-2286 PET uptake, it was comparable to FDG PET uptake across the 5 points (ratio to FDG PET = 1.0).
Observations:
68Ga-FAP-2286 is a potential imaging agent for a variety of malignancies, albeit its benefit is not universal. When compared to FDG PET, BC had the highest absolute and relative uptake, while prostate cancer had the lowest. Further research should be conducted to clarify the scenarios in which 68Ga-FAP-2286 PET may be used to guide therapeutic decision making, as well as which patients may benefit from FAP-targeted radioligand therapy. NCT04621435 is the clinical trial number.