Macrophage targeting with technetium-99m labelled J001 acylated poly-galactoside for scintigraphy of inflammation: Optimization and assessment of imaging specificity in experimental arthritis

Abstract

J001, an acylated poly-(1,3)-galactoside purified from the membrane ofKlebsiella pneumoniae, associates selectively with macrophages via the binding to CD11b and CD14 molecules. Inflammatory foci known to recruit macrophages could thus be imaged with technetium-99m labelled J001. This study aims to define the optimal scintigraphic protocol for^99mTc-J001 imaging and to evaluate the specificity of J001 scans. A dose range study was conducted in rabbits with immunological arthritis using six different specific activities ranging from 370 to 11840 MBq·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^99mTc-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. Specificity of the macrophage imaging was assessed by comparison with scans obtained after administration of^99mTcO₄ ⁻ or^99mTc-albumin nanocolloids. A protocol of plasma transfusion was also used to inject^99mTc-J001 after complete removal of radioactive colloids likely to be generated during the labelling. For the higher specific activities (5920 and 11840 MBq·mg⁻¹), radiochemical purity degradation and in vitro^99mTc transchelation were noted. To prevent transchelation and^99mTc bond hydrolysis likely to impair imaging specificity, 1480 MBq·mg⁻¹ corresponding to 25 µg injected J001 was found to be the optimal usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor involved in the J001 imaging of arthritis.