A Microdose PET Study of the Safety, Immunogenicity, Biodistribution, and Radiation Dosimetry of 18F-FB-A20FMDV2 for Imaging the Integrin αvβ6

Abstract

The αvβ6 integrin is involved in the pathogenesis of cancer and fibrosis. A radio-labelled 20-amino acid αvβ6-binding peptide, derived from the foot and mouth virus (A20FMDV2), has been developed to image αvβ6 levels pre-clinically. This study was designed to translate these findings into a clinical PET imaging protocol to measure the expression of αvβ6 in humans. Methods: Pre-clinical toxicology was undertaken and a direct immunoassay was developed for FB-A20FMDV2. A first time in human study of [¹⁸F]FB-A20FMDV2 was conducted in four healthy subjects (two males and two females). Each subject received a single microdose of [¹⁸F]FB-A20FMDV2. Subjects underwent a multibed positron emission tomography (PET) scan of the whole body over 3+ hours. Results: There were no findings in the pre-clinical toxicology assessments and no anti-A20FMDV2 antibodies were detected before or after dosing with the PET ligand. The mean and standard deviation of the administered mass of [¹⁸F]FB-A20FMDV2 was 8.7 ± 4.4 µg (range, 2.7–13.0 mg). The mean administered activity was 124 ± 20 MBq (range, 98–145 MBq). There were no adverse or clinically detectable pharmacologic effects in any of the [4] subjects. No significant changes in vital signs or the results of laboratory studies or electrocardiograms were observed. Uptake of radioactivity was observed in the thyroid, salivary glands, liver, stomach wall, spleen, ureters and bladder. Time-activity curves indicated that the highest activity was observed in the bladder content, followed by the kidneys, small intestine, stomach, liver, spleen, thyroid and gallbladder. The largest component of the residence times was the voided urine, followed by muscle, bladder and liver. Using the mean residence time over all subjects as input to Organ Level INternal Dosimetry Assessment/EXponential Modelling software (OLINDA/EXM), the effective dose was determined to be 0.0217 mSv/MBq; using residence times from single subjects gave a standard deviation of 0.0020 mSv/MBq from the mean. The critical organ was the urinary bladder, with an absorbed dose of 0.18 mGy/MBq. Conclusion: [¹⁸F]-FB-A20FMDV2 successfully passed toxicology criteria, showed no adverse effects in healthy subjects and has an effective dose that enables multiple scans in a single subject.