BARC/PUB/2016/0545

 
 

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

 
     
 
Author(s)

Satpati, D.; Arjun, C.; Krishnamohan, R.; Samuel, G.; Banerjee, S.
(RPhCS)

Source

Chemical Biology and Drug Design, 2016. Vol. 87 (5): pp. 680-686

ABSTRACT

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-SCNBz- NOTA. The two ciprofloxacin conjugates, CP-PASCN- Bz-DOTA (1) and CP-PA-SCN-Bz-NOTA (2), were radiolabeled with 68Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of 68Ga-1 and 68Ga-2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9–1.0% for 68Ga-1 and 1.6–2.3% for 68Ga-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 nonviable bacterial cells. Bacterial infection targeting efficacy of 68Ga-1 and 68Ga-2 was tested in vivo in rats where the infected muscle-to-inflamed muscle (68Ga-1: 2± 0.2, 68Ga-2: 3 ±0.5) and infected muscle-to-normal muscle ratios (68Ga-1: 3± 0.4, 68Ga-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 68Ga-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.

 
 
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