Technetium-99m-cyclam AK 2123: a novel marker for tumor hypoxia

Technetium-99m labeled cyclam N-2'-methoxyethyl-2-(3'-nitro-1'-triazole) acetamide (cyclam AK 2123) has been synthesized, radiolabeled and characterized as a hypoxic tumor imaging agent. Radiochemical purity was greater than 95%. Marker biodistribution was measured in normal Wistar strain rats at different time intervals after intra venous (i.v.) administration. In vivo distribution and scintigraphic imaging studies were performed after i.v. injection into mammary tumor-bearing rats using a gamma camera and associated computer. Intratumor partial oxygen pressure (pO(2)) and oxygen saturation measurements were performed to estimate the oxygenation status of the tumors. Tumor to muscle ratio (T/M) of Tc-99m-cyclam AK 2123 was 8.5 which was compared with other tumor seeking radiopharmaceuticals, viz. Tc-99m-(V) DMSA (3.07), Tc-99m-citrate (5.29) and (201)T1C1 (3.29). T/M ratios were also evaluated in comparison with radioiodinated iodoazomycin galactopyronoside (I-125-IAZG). The ratio obtained was 18 for Tc-99m-cyclam AK 2123 and 20 for I-125-IAZG, respectively. The increased concentration of radioactivity in these tumors suggests that this agent could be labelling hypoxic cells and have utility as an imaging agent. (C) 2000 Elsevier Science Ltd. All rights reserved.