Imaging experimental osteomyelitis using radiolabeled liposomes

We evaluated radiolabeled liposomes (liposomes labeled both with ^99mTc and ¹¹¹In) for the early detection of osteomyelitis in an experimental model. Methods: Liposomes, containing 5% polyethylene glycol- distearoyl phosphatidylethanolamine with encapsulated glutathione and deferoxamine, were prepared and labeled with ^99mTc and ¹¹¹In by a previously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and Staphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi 69^9mTc and 75-125 μCi ¹¹¹In), ^99mTc-methylene diphosphonate (MDP) (3-5 mCi) and ⁶⁷Ga- citrate (500 μCi), were performed starting at the third day after 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 histopathology. Results: For interpreting relative efficacy of individual radiopharmaceuticals, only animals showing positive histopathological findings (n = 9) were considered. Radiographs (Days 12, 13) were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though the lesion could be delineated as early as 8 hr postinjection in the ^99mTc window, the best target-to-nontarget ratio (T/NT) of 1.86 ± 0.19 was obtained at 48 hr in the ¹¹¹n window. Three-phase ^99mTc-MDP 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 results show liposomes are better than ^99mTc-MDP for imaging bone infection. Given the early localization and better quality of the images, radiolabeled liposomes also exhibited advantages over ⁶⁷Ga-citrate for detection of acute osteomyelitis.