A phase I study to evaluate the dosimetry and safety of [⁸⁹Zr]Zr-DFO-AP-101, a new antibody-based radiopharmaceutical to detect misfolded SOD1 in amyotrophic lateral sclerosis.

Abstract

PURPOSE: Misfolded superoxide dismutase-1 (mSOD1) is an abnormal protein observed in amyotrophic lateral sclerosis (ALS) and constitutes a therapeutic target. The present study evaluated the biodistribution, dosimetry, and safety of a new antibody-based radiopharmaceutical, [89Zr]Zr-DFO-AP-101, targeting mSOD1. METHODS: Seven control participants and one patient with ALS received 41 ± 3 MBq of [89Zr]Zr-DFO-AP-101. They were followed up with five whole-body positron emission tomography (PET) scans over 10 days. Semi-automatic segmentation was performed on the images to derive time-activity curves, radiotracer effective half-life and dose exposure. RESULTS: Total elimination of the radiotracer (urinary and hepatobiliary) was 25–30% after three days and reached a plateau after a week. At 2 h post-injection, ~ 60% of the radiopharmaceutical remained in the blood pool, with a biological half-life of 53 h. The liver was the dose-limiting organ with 0.84 mSv/MBq in males, 1.07 mSv/MBq in females, and 1.23 mSv/MBq in the female ALS patient. The spleen, adrenal glands, kidney, and heart wall were the other most irradiated organs. Average effective doses were 0.21 mSv/MBq for males, 0.28 mSv/MBq for females, and 0.31 mSv/MBq for the female ALS patient. Tracer uptake in the spinal cord and vertebrae of the ALS patient, on Days 7 and 10, was more than one standard deviation higher than for the control female participants. No serious adverse event was observed. CONCLUSIONS: The single dose of [89Zr]Zr-DFO-AP-101 was safe for all participants. It provided good image quality for the biodistribution and dosimetry analysis over 10 days. Further studies are needed to demonstrate the efficacy of ALS diagnosis through PET imaging. https://www.clinicaltrials.gov/study/NCT05974579.