Abstract
1173
Objectives Uptake of F-18 FDG in highly glycolytic areas could not differentiate infection and/or inflammation which cause false positive results. An alternative way is to target cell proliferation via nucleoside analogues. This study was aimed to synthesis a guanine analog for cell nucleus activity assessment.
Methods N4-Guan is synthesized through a 9-step reaction. The hydroxyl groups of penciclovir was selectively protected. The unprotected hydroxyl group was converted to an amino group. The carboxyl acid group of the N4 mono-acid was reacted with amino-penciclovir to form amide linage. N4amG was obtained after deprotection and purification. Radiolabeling of N4amG with Tc-99m was performed in a standard manner. Cell uptake assay and cytoplasm/nucleus isolation was performed using breast cancer cell line. Biodistribution and planar imaging (n=3/time interval) of Tc-99m N4amG were conducted in breast tumor-bearing rats from 0.5-4hrs. Computer outlined region of interest (counts per pixel) was used to determine tumor-to-muscle (T/M) count density ratios. Dosimetry estimates were computed from respective biodistribution data using Olinda software.
Results Mass spectronmetry, NMR and HPLC analysis for N4amG were performed to determine the structure. The purity was >97%. The total synthetic yield was 6%. Radiochemical purity of Tc-99m N4amG determined by ITLC was >95% (in saline). There was 2.3%ID uptake in cytoplasm and 1.5%ID in nucleus after 4 hours incubation indicated Tc-99m N4amG was involved in cell nucleus activity. In the breast tumor-bearing rat planar imaging from 0.5-4 hours, T/M ratio was 3.65+0.18 to 5.02+0.41. In the rat biodistribution from 0.5-4hrs, tumor, tumor/blood and tumor/muscle count density ratios were 0.32+0.06 to 0.43+0.04, 0.29+0.02 to 0.52+0.02 and 3.24+0.38to 4.30+0.59, respectively. Tc-99m N4amG showed total rad absorbed by each organ was below the proposed annual and total limits after dosimetry estimation.
Conclusions Our data indicate that it is feasible to assess tumor nucleus activity with Tc-99m N4amG.