IMAGING EXPERIMENTAL OSTEOMYELITIS USING RADIOLABELED LIPOSOMES

We evaluated radiolabeled liposomes (liposomes labeled both with (TC)- T-99m and In-111) for the early detection of osteomyelitis in an exper imental model. Methods: Liposomes, containing 5% polyethylene glycol-d istearoyl phosphatidylethanolamine with encapsulated glutathione and d eferoxamine, were prepared and labeled with Tc-99m and In-111 by a pre viously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and St aphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi Tc-99m and 75-12 5 mu Ci In-111), Tc-99m-methylene diphosphonate (MDP) (3-5 mCi) and Ga -67-citrate (500 mu Ci), were performed starting at the third day afte r injection. Each radionuclide study was separated by at least 2 days. The animals also underwent radiography of the lower extremities. The animals were then killed and the infected tibia was excised for histop athology. Results: For interpreting relative efficacy of individual ra diopharmaceuticals, only animals showing positive histopathological fi ndings (n = 9) were considered. Radiographs (Days 12, 13) were conclus ive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Thoug h the lesion could be delineated as early as 8 hr postinjection in the Tc-99m window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained at 48 hr in the In-111 window. Three-phase Tc-99m-MD P scan (Day 7) was positive in only 5 rabbits with 3 hr T/NT of 1.6 +/ - 0.23. Galium-67-citrate images (Days 9-11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74 +/- 0.24. These res ults show liposomes are better than Tc-99m-MDP for imaging bone infect ion. Given the early localization and better quality of the images, ra diolabeled liposomes also exhibited advantages over Ga-67-citrate for detection of acute osteomyelitis.