Comparison of 99mTc-alafosfalin and 67Ga-citrate in a mouse model of bacterial infection

The antibiotic-peptide (99m)Tc-alafosfalin was assessed as an infection imaging agent in Staphylococcus aureas infected mice by comparison with (99m)Ga-citrate, and also examined for influence of septic status on tracer biodistribution by comparison with normal mice.

Intramuscular doses of S. aureus were administered into the right thigh muscle of mice and the infection was allowed to develop for 20 hours. In separate experiments, (99m)Tc-alafosfalin and (67)Ga-citrate were subsequently administered and allowed to localise. Quantitative organ distribution studies were performed in conjunction with scintigraphic images at 1 and 4 hours post injection. An additional biodistribution with (99m)Tc-alafosfalin in normal mice was also performed.

(99m)Tc-alafosfalin was predominantly renal excreted, with low liver, intestine and bone uptake. There was no difference in the uptake of these organs when infected mice were compared with normal mice. (99m)Tc-alafosfalin activity in the intestine at 1 and 4 hours was substantially less than (67)Ga-citrate. For (99m)Tc-alafosfalin, infected/non-infected thigh ratios of 2.8/1.0 and 3.6/1.0 were determined at 1 and 4 hours post injection respectively. (67)Ga-citrate gave ratios of 1.6/1.0 and 3.7/1.0 at the corresponding time points.

(99m)Tc-alafosfalin uptake was more rapid than (67)Ga-citrate, yet diffuse at the infectious sites in mice. The small and juvenile mouse model resulted in uptake of the phosphonic acid tracer by active bone growth areas which may be a disadvantage. This (99m)Tc-antibiotic peptide has potential as an infection imaging agent, and will be investigated further in another rodent infection model in the future.