Validation of Radiosynthesis and First in-Human Dosimetry of ⁶⁸ Ga-NOTA-UBI-29-41: A Proof of Concept Study

<b><i>Background:</i></b> Antimicrobial peptides (AMPs) such as UBI-29-41 offer a distinctive approach for precise detection due to their unique interactions with bacteria and makes them promising candidates for specific and selective imaging. The study was aimed to corroborate the in-house manual synthesis of ⁶⁸Ga-NOTA-UBI-29-41, evaluate its uptake in patients with suspected infection, and estimate of patient-specific dosimetry to ensure optimal clinical application. <b><i>Materials and Methods:</i></b> ⁶⁸Ga-NOTA-UBI-29-41 was synthesized by using a variable amount of UBI-29-41 (60-90 μg) to 555 MBq of ⁶⁸Ga in 0.05 M hydrochloric acid (HCl) and heating the reaction sample for 12 min at 90°C at pH: 3.5-4 to obtain the radiopeptide with high yield and high radiochemical purity (RCP). ⁶⁸Ga-NOTA-UBI-29-41 positron emission tomography/computed tomography (PET/CT) scans at variable timepoints were done to evaluate its biodistribution and maximum uptake time. Furthermore, patient-specific dosimetric estimation was done using the HERMES software. <b><i>Results:</i></b> A total of 5 μg/37 MBq (5 μg/mCi) of NOTA-UBI-29-41 for 12 min at 90°C were the optimal parameters to obtain 88%-90% of yield and 98%-99 % of RCP. ⁶⁸Ga-NOTA-UBI-29-41 showed expeditious blood clearance and high renal excretion. The optimal time for imaging of infection with ⁶⁸Ga-NOTA-UBI-29-41 was found to be at 60 min postinjection (<i>n</i> = 8). The critical organ was the urinary bladder, receiving an average dose of 138.02 ± 45.92 µSv/MBq, followed by 53.81 ± 13.72 µSv/MBq for kidneys with a mean effective dose of 1.52 ± 0.64 mSv. <b><i>Conclusion:</i></b> The protocol for in-house manual labeling of ⁶⁸Ga-NOTA-UBI-29-41 was reproducible, providing high yield and RCP. ⁶⁸Ga-NOTA-UBI-29-41 administration was found to be safe and nontoxic. The favorable biodistribution and the first-in-human patient-specific dosimetry ensure optimal clinical application.