Synthesis and preliminary evaluation of 99mTc-spermine as a tumor imaging agent

Abstract

Polyamines are essential for the growth and survival of all cells with biosynthesis and transportation of polyamines being very active in tumors. With the aim of developing a new tumor imaging agent, the endogenous polyamine, spermine was labeled with 99mTc, and its characters were also evaluated via in vitro and in vivo studies. 99mTc-labeled spermine probe (99mTc-spermine) was synthesized by the direct pretinning procedure and the labeling procedure was optimized with regard to the pH, reaction time, amounts of spermine and SnCl2. The stability of the 99mTc-spermine and its capacity to accumulate into 4T1 tumor cells were also evaluated. Biodistribution of 99mTc-spermine was studied in 4T1 tumor-bearing mice. In the optimal conditions, the whole radiosynthesis was accomplished within 10 min with a decay-corrected yield of 96.5 ± 1.3 % and radiochemical purity of >95 %.99mTc-spermine was stable at both 37 and 4 °C for at least 6 h. In vitro tests revealed that the ability of 99mTc-spermine to penetrate in 4T1 tumour cells and an excess of spermine blocked the accumulation of the compound in the models. Biodistribution studies showed a high tumor uptake peaked at 30 min post-injection with 1.82 ± 0.19 % ID%/g. The tumor to muscle uptake ratios of the probe were 3.60 ± 0.51, 4.48 ± 0.29, 4.82 ± 0.18, 5.64 ± 0.10, respectively at 30 min, 1, 2 and 4 h postinjection. Block studies indicated that 99mTc-spermine had specific binding of tumor via polyamine transport systems. 99mTc-spermine is a promising radiopharmaceutical in tumor imaging. Further studies are required to determine the usability of 99mTc–spermine for diagnosis purposes.