68 Ga‐labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection

• Published in: Chemical biology & drug design Vol. 87; no. 5; pp. 680 - 686
• Main Authors: Satpati, Drishty, Arjun, Chanda, Krishnamohan, Repaka, Samuel, Grace, Banerjee, Sharmila
• Format: Journal Article
• Language: English
• Published: 01.05.2016
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12701

With an aim of developing a bacteria‐specific molecular imaging agent, ciprofloxacin has been modified with a propylamine spacer and linked to two common bifunctional chelators, p‐ SCN ‐Bz‐ DOTA and p‐ SCN ‐Bz‐ NOTA . The two ciprofloxacin conjugates, CP ‐ PA ‐ SCN ‐Bz‐ DOTA ( 1 ) and CP ‐ PA ‐ SCN ‐Bz‐ NOTA ( 2 ), were radiolabeled with 68 Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of 68 Ga‐ 1 and 68 Ga‐ 2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9–1.0% for 68 Ga‐ 1 and 1.6–2.3% for 68 Ga‐ 2 ) could not be blocked in the presence of excess amount of unlabeled ciprofloxacin. However, uptake of radiotracers in live bacterial cells was significantly higher (p < 0.01) than that in non‐viable bacterial cells. Bacterial infection targeting efficacy of 68 Ga‐ 1 and 68 Ga‐ 2 was tested in vivo in rats where the infected muscle‐to‐inflamed muscle ( 68 Ga‐ 1 : 2 ± 0.2, 68 Ga‐ 2 : 3 ± 0.5) and infected muscle‐to‐normal muscle ratios ( 68 Ga‐ 1 : 3 ± 0.4, 68 Ga‐ 2 : 6.6 ± 0.8) were found to improve at 120 min p.i. Fast blood clearance and renal excretion was observed for both the radiotracers. The two 68 Ga‐labeled infection targeting radiotracers could discriminate between bacterial infection and inflammation in vivo and are worthy of further detailed investigation as infection imaging agents at the clinical level.