SYNTHESIS OF 3 NO CARRIER-ADDED O-6-4-[I-125]IODOBENZYLGUANOSINE DERIVATIVES, NEW REAGENTS FOR THE ASSAY OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY

O-6-alkylguamine-DNA alkyltransferase (AGT) is mainly responsible for tumour resistances observed in chemotherapeutic treatments by chloroet hylnitrosoureas (CENUs). Measurement of AGT activity is thereby essent ial to predict the response of the patients to therapy with CENUs. In order to develop a sensitive and easy new assay for AGT, previously un described O-6-4-[I-125]iodobenzyl-2'-deoxyguanosine, O-6-4-[I-125]iodo benzyl-N-acetylguanosine and O-6-4-[I-125] iodobenzylguanosine labelle d with high specific activity were prepared. The most convenient synth etic route appeared to be a rapid and high yield iododestannylation of a tri-n-butylstamyl derivative with no-carrier-added sodium [I-125] i odide. Final HPLC separation from the excess of precursor and unreacte d [I-125] iodides afforded the radioiodinated guanosine derivatives in yields ranging from 70 to 77%, chemical and radiochemical purities av eraging 99%.