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

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.