DETECTING INFECTION AND INFLAMMATION WITH TC-99M-LABELED STEALTH(R) LIPOSOMES

The performance of Tc-99m Stealth(R) liposomes was investigated in var ious rat models, Methods: Preformed polyethyleneglycol-containing lipo somes with encapsulated reduced glutathione, were radiolabeled using t he lipophilic Tc-99m-HMPAO. The labeled liposomes were intravenously a dministered to rats with focal S. aureus or E. coli infection, or turp entine-induced inflammation. For comparison, Tc-99m-nanocolloid- and T c-99m-labeled nonspecific IgG were tested, In rats with Pneumocystis c arinii pneumonia (PCP), Tc-99m-liposomes were directly compared to In- ill labeled nonspecific IgG. Results: Technetium-99m-liposomes accumul ated in the infectious and inflammatory muscle foci over 24 hr (0.59% injected dose per gram tissue (%ID/g) for E. coli; 0.98%ID/g for S. au reus; 1.18%ID/g for turpentine), Abscess-to-muscle ratios increased to values as high as 24.0, 41.7 and 44.5 for the respective models at 24 hr postinjection, Technetium-99m-liposomes visualized the foci as ear ly as 1 hr postinjection. Technetium-99m-IgG visualized S. aureus infe ction, but abscess-to-muscle ratios and abscess uptake at the later ti me points were significantly lower, Technetium-99m-nanocolloid failed to visualize any of the muscle foci. In PCP however, Tc-99m-liposomes did not show preferential localization in the infection, The control a gent In-111-lgG showed a significant, two-fold increase in lung uptake . Conclusion: Technetium-99m-Stealth(R) liposomes preferentially accum ulated in abscesses, leading to very high target-to-nontarget ratios, This property appears to be related to a process based on uptake of lo ng-circulating particles, In a specific type of infection, i.c. PCP, T c-99m-liposomes did not accumulate in diseased lung tissue, thus mimic king the in vivo behavior of labeled leukocytes.