Markers of Tumor Cell Proliferation

Noninvasive imaging assessment of tumor cell proliferation could be helpful in the evaluation of tumor growth potential, the degree of malignancy, and could provide an early assessment of treatment response prior to changes in tumor size.99mTc-EC-adenosine and 99mTc-EC-guanosine analogs were synthesized for this purpose. These radioligands could improve the understanding of the biological behavior of malignant tumors, and lead to better prognostic evaluation, treatment follow-up, and patient management. To assess tumor proliferative activity and cellular uptake, autoradiographs and radionuclide imaging of these ligands were performed.

Figure 20 In vitro cell culture assays indicate more uptake in PC-3 cells (androgen independent) than LNCap cells (androgen dependent).

The synthesis of EC-guanosine analog (EC-Guan) is shown in Fig. 22. In vitro thymidine incorporation assays indicated that 99mTc-EC-Guan was involved in DNA/RNA cell nuclei activities (Fig. 23). Cellular uptake of 99mTc-EC-Guan was time dependent and proportional to cellular uptake (Fig. 24). Such an agent has also been used as a reporter molecule for HSV-tk expression in reporter-gene constructs. In this setting, the herpes simplex thymidine kinase phosphorylates 99mTc-EC-Guan leading to accumulation within the cell. Thus,99mTc-EC-Guan acts as a "reporter" for the presence of HSV-tk and other genes cotransfected with the same viral transcript. There was no marked difference in cellular uptake of 99mTc-EC-Guan pre- and post-viral transfection of prostate cancer cells (Fig. 25). Planar imaging in tumor-bearing rabbits showed that tumors could be visualized with

Figure 21 Planar images of breast tumor-bearing rats after administration of 99mTc-EC and 99mTc-EC-LHRH (100 mCi/rat, IV) show that the tumor could be well visualized from 0.5 to 2 hours post injection.
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