The high-LET conversion electron (C.E.) emitter Sn-117m (t� 14d, ? 159keV, 86%), in addition to being a good therapeutic agent for cancer, also shows considerable promise for the noninvasive molecular imaging and treatment of active atheromatous disease [vulnerable plaque (VP), also known as thin-cap fibroatheroma (TCFA)], in the coronary and carotid arteries. The VP's form below the lumen in coronary artery walls, and inflammation is the main driver. Unfortunately, a majority of all significant cardiac events (~70%) leading to MI, including sudden death, are caused by the rupture of these thin-cap fibroatheroma lesions, not lumen atherosclerosis. The C.E. from Sn-117m are ideal for treating VP's, as their discrete range in tissue (~300 �m) is approximately the same as the VP thickness in human carotid and coronary arteries. We have developed and used (i) Sn-117m electroplated coronary stents (Sn-117m stents), and (ii) Sn-117m-DOTA �Annexin [TA] for evaluating the possibility of simultaneous imaging and therapy of VP with this dual-purpose (theragnostic) radionuclide.The TA was synthesized by attaching Sn-117m to a bifunctional chelating agent (aminobenzyl-DOTA) using a microwave reactor at elevated temperatures and then purified using HPLC. Conjugation of this chelate to the biological molecule (annexin V-128) was accomplished by preparing the isothiocyanate version of the chelate and then reacting it with lysine residues on the annexin for 90 min at 37�C. Several analytical methods (cell binding, electrophoresis, gel permeation chromatography) were used to evaluate the cGMP TA that was produced.Studies in a hyperlipidemic rabbit model, 3d after Sn-117m- stent implantation [4 doses: 0 (cold tin), 30, 60, and 150�Ci Sn-117m per 15-mm stent], upon histochemical analysis of proliferating macrophages and smooth muscle cells, demonstrated that inflammatory cells in the Sn-117m-stented segments were dramatically reduced in a dose-dependent manner. In recent studies in an Apo-E mouse VP model, systemically administered TA has demonstrated a significant anti-inflammatory therapeutic effect. The plaque composition showed significantly less expression of macrophages in all treatment groups as compared to the control group. A phase I clinical trial with TA, in which human carotid endarterectomy patients were dosed and imaged for VP, with histology as the comparison, has demonstrated promising results.

Enabling personalized medicine: Simultaneous imaging and treatment with tin-117m based radiopharmaceuticals

248th National Meeting (2014)

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