First-in-human evaluation of 68Ga-FAP-2286, a fibroblast activation protein targeted radioligand (2024)

Abstract

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Introduction: 68Ga-FAP-2286 is a novel imaging agent under investigation for its ability to detect metastatic disease in patients with solid tumors. 68Ga-FAP-2286 is a peptidomimetic molecule that targets fibroblast activation protein (FAP), a transmembrane protein highly expressed in cancer-associated fibroblasts (CAFs). CAFs are present in many solid tumors, making FAP an ideal target for detecting sites of metastasis across a range of cancer types. Here, we present initial, first-in-human data on safety, biodistribution, and image quality in patients who received 68Ga-FAP-2286 (NCT04621435).

Methods: From December 2020 through December 2021, 26 patients were imaged by PET/CT or PET/MRI at a single center. On the day of imaging, patients were injected with 5.9 ± 1.3 mCi of 68Ga-FAP-2286 60 ± 13 minutes before scanning. Patients underwent pre- and post-imaging lab evaluations, physical exams, vital signs assessments, and ECGs to evaluate safety. Adverse event assessments were performed on the day of imaging and again 1-3 days later. Enrolled patients were grouped by administered dose ranges of 3-4.5 mCi (n=6), 4.5-6.5 mCi (n=10), and 6.5-8 mCi (n=10). The mean and standard deviation of the SUVmean in the kidneys, liver, spleen, and blood pool were recorded to investigate biodistribution and image quality. For qualitative analysis of image quality, images were graded on a five point Likert Scale (from 1-non-diagnostic to 5-good image quality). For quantitative analysis, the noise in the liver and blood pool were measured, where noise was defined as the standard deviation of the organ or blood pool divided by the mean.

Results: Among 26 participants, no serious adverse events were reported. Lab evaluations, physical exams, vital signs, and ECGs showed no clinically significant changes after imaging. Average SUVmean ± SD in the kidneys, liver, spleen, and blood pool was 4.6 ± 1.6, 2.2 ± 0.9, 1.0 ± 0.4, and 1.4 ± 0.4, respectively. The average uptake in tumor versus background (tumor-to-background ratio) was 14.4 (Figure 1). All images received Likert scores ≥ 4, consistent with diagnostic quality scans, with average scores of 4.8, 4.4, and 4.7 in the 3-4.5 mCi, 4.5-6.5 mCi, and 6.5-8 mCi dose groups. Likert scores stratified by scanner were 4.9 for PET/CT and 4.3 for PET/MRI. Noise measurements in the liver were 0.16 ± 0.04, 0.22 ± 0.08, and 0.16 ± 0.09 in patients who received 3-4.5 mCi, 4.5-6.5 mCi, and 6.5-8 mCi. Noise measurements in the blood pool were 0.20 ± 0.06, 0.26 ± 0.08, and 0.17 ± 0.07 in patients administered with 3-4.5 mCi, 4.5-6.5 mCi, and 6.5-8 mCi. There were no differences in noise measurements in the liver across dose groups (P > 0.05). In the blood pool, noise was higher in patients dosed with 4.5-6.5 mCi compared to 6.5-8 mCi (P = 0.025) but equivalent between all other groups.