Radiolabeling, quality control, and biological characterization of 177Lu‐labeled kanamycin

• Published in: Chemical biology & drug design 2017-09, Vol.90 (3), p.425-431
• Main Authors: Akbar, Muhammad Usman, Bokhari, Tanveer Hussain, Khalid, Muhammad, Ahmad, Muhammad Razeen, Roohi, Samina, Hina, Saira, Mehmood, Sajid, Sohaib, Muhammad, Jabbar, Tania
• Format: Article
• Language: English
• Subjects: 177Lu‐kanamycin; biodistribution; electrophoresis; HPLC; quality control; radiolabeling; scintigraphy
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12960

Kanamycin is an antibiotic, isolated from Streptomyces kanamyceticus, which is used to treat serious bacterial infections. The fact that the present radioligand 99mTc‐kanamycin used for diagnosis is short‐lived, raised a need to label and study kanamycin with one of the most important beta (β) radiation emitting isotope 177Lu. Labeling yield of 177Lu‐kanamycin was confirmed by different chromatography techniques such as paper chromatography, TLC, HPLC. Several experiments were performed to optimize labeling with changing reaction conditions such as pH, temperature, amount of ligand, and reaction time. In vitro stability analysis was performed incubation with human serum. Electrophoresis analysis was also conducted to determine the charge on 177Lu‐kanamycin. The biodistribution and scintigraphy were performed in normal mice and rabbit, respectively, at different time intervals of postinjection. 177Lu‐kanamycin was prepared with very high yield (~100%), with excellent stability in vivo and in vitro (>99% 6 hr postprep.), at pH 7. Maximum labeling was achieved at less reaction time (15 min), with maximum conjugation of the ligand (12.5 mg) with 177Lu. Electrophoresis analysis showed net neutral charge. The radioligand showed rapid clearance from body in biodistribution and scintigraphy studies. The preparation 177Lu‐kanamycin could be used as a radio‐pharmaceutical for infection imaging purpose, especially when transporting the radioligand to long‐range distances. 99mTc‐kanamycin, used for bacterial infection imaging, is short‐lived and cannot be transported over long distances. To resolve this, kanamycin was labeled with lutetium‐177, a long‐lived isotope that emits β‐ and γ‐radiation. Radiolabeling of 177Lu‐kanamycin was optimized. 177Lu‐kanamycin was prepared with a very high yield (~100%) and showed excellent stability in vitro. Biodistribution and scintigraphy studies in mice and rabbit showed rapid clearance from body, suggesting that 177Lu‐kanamycin could be used for medical imaging.