With the aim to develop beneficial tracers for cerebral
tumors, we tested two novel
5-iodo-2'-deoxyuridine (
IUdR) derivatives, diesterified at the
deoxyribose residue. The substances were designed to enhance the uptake into
brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3',5'-di-O-acetyl-2'-
deoxyuridine (Ac2[125I]
IUdR), 5-[125I]iodo-3',5'-di-O-pivaloyl-2'-
deoxyuridine (Piv2[125I]
IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human
thymidine phosphorylase.
DNA integration of each tracer was determined in 2
glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted
brain tumors. Ac2[125I]
IUdR, Piv2[125I]
IUdR and [125I]
IUdR (control) were prepared with labeling yields of 31-47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by
thymidine phosphorylase. Ac2[125I]
IUdR and Piv2[125I]
IUdR were specifically integrated into the
DNA of all tested tumor cell lines but to a less extend than the control [125I]
IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]
IUdR>Ac2[125I]
IUdR>[125I]
IUdR. For Ac2[125I]
IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced
brain tumors, the uptake ratios of
tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]
IUdR, Ac2[125I]
IUdR and Piv2[125I]
IUdR, respectively. Esterifications of both deoxyribosyl
hydroxyl groups of the
tumor tracer
IUdR lead to advantageous properties regarding uptake into
brain tumor tissue and metabolic stability.