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Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

INTRODUCTION: [(111)In]XYIMSR-01 is a promising single-photon emission computed tomography (SPECT) imaging agent for identification of tumors that overexpress carbonic anhydrase IX. To translate [(111)In]XYIMSR-01 to phase I trials, we performed animal toxicity and dosimetry studies, determined the maximum dose for human use, and completed the chemistry, manufacturing and controls component of a standard regulatory application. METHODS: The production process, quality control testing, stability studies, and specifications for sterile drug product release were based on United States Pharmacopeia chapters and , FDA 21 CFR part 212. Toxicity was evaluated by using non-radioactive [(113/115)In]XYIMSR-01 according to 21 CFR part 58 guidelines. OLINDA/EXM was used to calculate the maximum single dose for human studies. RESULTS: Three process validation runs at starting radioactivities of ~ 800 MBq were completed with a minimum concentration of 407 MBq/mL and radiochemical purity of ≥ 99 % at the end-of-synthesis. A single intravenous dose of 55 μg/mL of [(113/115)In]XYIMSR-01 was well-tolerated in male and female Sprague-Dawley rats. The calculated maximum single dose for human injection from dosimetry studies was 390.35 MBq of [(111)In]XYIMSR-01. CONCLUSION: We have completed toxicity and dosimetry studies as well as validated a manufacturing process to test [(111)In]XYIMSR-01 in a phase I clinical trial.

Additional file 1: Table 1. Patients’ Characteristics Data.

Pharmacokinetic model equations for premature infants and newborn through 5-year-olds. Equations from SAAM II compartment model used to derive TIAC in each source tissue (or sample) for brain, lungs, heart wall, kidneys, and liver are also provided. For each source organ or each sample, qi represents the differential equations created internally and solved by SAAM II. (DOCX 290 kb)

Pharmacokinetic model equations for premature infants and newborn through 5-year-olds. Equations from SAAM II compartment model used to derive TIAC in each source tissue (or sample) for brain, lungs, heart wall, kidneys, and liver are also provided. For each source organ or each sample, qi represents the differential equations created internally and solved by SAAM II. (DOCX 290 kb)