| Abstract: | The biodistribution of radiolabelled 1-(2'-fluoro-2'-deoxy-beta-D-ribofuranosyl)uracil (2'-FUdR) and 1-(2'-chloro-2'-deoxy-beta-D-ribofuranosyl)uracil (2'-ClUdR) was evaluated using in-vivo and in-vitro tumour models. 6-[3H]-2'-FUdR exhibited a maximum tumour:blood (T:B) ratio (Walker 256 carcinosarcoma) of 1.0 at 15 min after injection whereas 2-[14C]-2'-FUdR and 2'-[36Cl]-2'-ClUdR exhibited maximum T:B ratios (Lewis lung carcinoma) of 3.0 and 4.1 respectively at 120 min. Clearance of blood radioactivity after injection of 6-[3H]-2'-FUdR, 2-[14C]-2'-FUdR and 2'-[36Cl]-2'-ClUdR was rapid and best described by a biexponential function. The clearance half-lives of the short-lived components were calculated as 1.6 min (95.5%), 2.3 min (94.7%) and 1.2 min (96.0%) respectively. The clearance half-lives of the long-lived components were 23 h (4.5%) for 6-[3H]-2'-FUdR, 89 min (5.3%) for 2-[14C]-2'-FUdR, and 49 min (4.0%) for 2'-[36Cl]-2'-ClUdR. Less than 36% of the 14C radioactivity present in the urine 2 h after injection of 2-[14C]-2'-FUdR was associated with 2'-FUdR, whereas greater than 91% of the 36Cl radioactivity in the urine 2 h after injection of 2'-[36Cl]-2'-ClUdR was associated with 2'-ClUdR. Both 6-[3H]-2'-FUdR (less than 3.1 pmol/10(6) cells) and 6-[3H]-2'-ClUdR (1.0 +/- 0.2 pmol/10(6) cells) were incorporated into cultured Raji tumour cells in vitro to a lesser extent than the natural nucleosides uridine (137.2 +/- 3.8 pmol/10(6) cells) and 2'-deoxyuridine (23.5 +/- 2.5 pmol/10(6) cells) after a 20 min incubation. |
