MACROPHAGE TARGETING WITH TC-99M LABELED J001 ACYLATED POLY-GALACTOSIDE FOR SCINTIGRAPHY OF INFLAMMATION - OPTIMIZATION AND ASSESSMENT OF IMAGING SPECIFICITY IN EXPERIMENTAL ARTHRITIS

J001, an acylated poly-(1,3)-galactoside purl fled from the membrane o f Klebsiella pneumoniae, associates selectively with macrophages via t he binding to CD11b and CD14 molecules. Inflammatory foci known to rec ruit macrophages could thus be imaged with technetium-99m labelled J00 1. This study aims to define the optimal scintigraphic protocol for Tc -99m-J001 imaging and to evaluate the specificity of J001 scans. A dos e range study was conducted in rabbits with immunological cal arthriti s using six different specific activities ranging from 370 to 11840 MB q . mg(-1) while the intravenously injected activity was constant (37 MBq) Radiochemical purity for each preparation was documented together with the in vivo stability of the Tc-99m-J001 complex using exclusion -diffusion radioHPLC of serum collected 1 h after radiopharmaceutical administration. Scintigraphic images were recorded at 2, 3 and 4 h and analysed using indexes calculated from regions of interest. Specifici ty of the macrophage imaging was assessed by comparison with scans obt ained after administration of (TCO4-)-T-99m or (TC)-T-99m-albumin nano colloids. A protocol of plasma transfusion was also used to inject Tc- 99m-J001 after complete removal of radioactive colloids likely to be g enerated during the labelling. For the higher specific activities (592 0 and 11840 MBq . mg(-1)), radiochemical purity degradation and in vit ro Tc-99m transchelation were noted. To prevent transchelation and Tc- 99m bond hydrolysis likely to impair imaging specificity, 1480 MBq . m g(-1) corresponding to 25 mu g injected J001 was found to be the optim al usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor i nvolved in the J001 imaging of arthritis.