TY - JOUR T1 - <sup>68</sup>Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 334 LP - 339 DO - 10.2967/jnumed.117.200048 VL - 59 IS - 2 AU - Thomas Ebenhan AU - Mike M. Sathekge AU - Thabo Lengana AU - Michel Koole AU - Olivier Gheysens AU - Thavendran Govender AU - Jan R. Zeevaart Y1 - 2018/02/01 UR - http://jnm.snmjournals.org/content/59/2/334.abstract N2 - Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has been functionalized with NOTA to allow complexation to 68Ga (68Ga-NOTA-UBI). We herein assess the cytotoxicity and radiation dosimetry for 68Ga-NOTA-UBI and a first-in-human evaluation to diagnose infectious processes. Methods: Cytotoxicity was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes. Tracer susceptibility was studied in vitro using different bacterial and fungal strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry were performed on nonhuman primates. Two healthy volunteers and 3 patients with suspected infection underwent 68Ga-NOTA-UBI PET/CT imaging. Results: Negligible cytotoxicity was determined for NOTA-UBI. 68Ga-NOTA-UBI showed moderate blood clearance (29-min half-life) and predominant renal clearance in nonhuman primates. Human radiation dose estimates indicated the bladder wall as the dose-critical tissue (185 μSv/MBq), followed by the kidneys (23 μSv/MBq). The total absorbed body dose was low (&lt;7 μSv/MBq); the effective dose was estimated at 17 μSv/MBq. 68Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3 patients. Conclusion: 68Ga-NOTA-UBI is considered a nontoxic, safe-to-administer radiopharmaceutical unlikely to cause adverse effects in humans. The favorable tracer biodistribution and the first-in-human results will make 68Ga-NOTA-UBI PET/CT an encouraging future diagnostic technique with auxiliary clinical relevance. ER -