(68) Ga-labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection.
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| 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-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.
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| Authors | Drishty Satpati, Chanda Arjun, Repaka Krishnamohan, Grace Samuel, Sharmila Banerjee |
| Journal | Chemical biology & drug design (Chem Biol Drug Des) Vol. 87 Issue 5 Pg. 680-6 (May 2016) ISSN: 1747-0285 [Electronic] England |
| PMID | 26647765 (Publication Type: Journal Article) |
| Copyright | © 2015 John Wiley & Sons A/S. |
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