Biodistribution studies of Tc-99m-labeled myoblasts in a murine model of muscular dystrophy

The purpose of this study was twofold: first, to evaluate the myoblast labe ling of various Tc-99m complexes and to select the complex that best accomp lishes this labeling, and second to evaluate the biodistribution of myoblas ts labeled with this complex using mice with MDX muscular dystrophy (the mu rine homologue of Duchenne's muscular dystrophy). The following ligands wer e used to prepare the corresponding Tc-99m complexes: hexakis-methoxy-isobu tyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4, 8-diaza-3,6,6,9-tetramethyl-undecane-2, 10-dione-bisoxime (HM-PAO), bis(N-e thyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt ). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the Tc-99m complexes prepared from the above ligands. Viability wa s assessed by microscopic counting after trypan blue staining, and the radi oactivity absorbed in the cells was measured after centrifugation. The comp ound with the highest uptake in cellular pellets was [Tc-99m]N-NOEt. The bi odistribution of myoblasts labeled with this complex was evaluated after in traaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles la cking dystrophin. (C) 2001 Elsevier Science Inc. All rights reserved.