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Imaging Experimental Osteomyelitis Using Radiolabeled Liposomes

Department of Radiology and Lab Animal Resources, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Correspondence: For correspondence or reprints contact: William T. Phillips, MD, Department of Radiology, Universfty of Texas Health Science center at San Antonio, 7703 Floyd Curl Dr., San Antonio, Texas 78284.

ABSTRACT

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 ¹¹¹I and 75–25 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 ¹¹¹In 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.

Key Words: osteomyelitis • liposomes • technetium-99m • infection imaging

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