Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine

Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in v ivo degradation and low DNA-incorporation rates. We evaluated whether block ing of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuri dine (IdUrd). We first show in vitro that coincubation with FdUrd substanti ally increased incorporation of [I-125]IdUrd and [H-3]dThd in the three tes ted human glioblastoma lines. Flow cytometry analysis showed that a short c oincubation with FdUrd (I h) produces a signal increase per labeled cell. W e then measured biodistribution 24 h after Lv. injection of [I-125]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared wit h animals given [I-125]IdUrd alone, Lv. preadminsitration for I h of 10 mg/ kg FdUrd increased the uptake of [I-125]IdUrd in the three tumors 4.8-6.8-f old. Compatible with previous reports, there were no side effects in mice o bserved for 2 months after receiving such a treatment. The tumor uptake of [I-125]IdUrd was increased less than or equal to 13.6-fold when FdUrd pread ministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained l ower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bon e marrow, spleen, and intestine) and negligible in quiescent tissues. DNA e xtraction showed that 72-80% of radioactivity in tumor and intestine was bo und to DNA. Scintigraphy of xenografted mice was performed at different tim es after Lv. injection of 3.7 MBq [I-125]IdUrd. Tumor detection was signifi cantly improved after FdUrd preadministration while still equivocal after 2 4 h in mice given [I-125]IdUrd alone. Furthermore, background activity coul d be greatly reduced by p.o. administration of KClO4 in addition to potassi um iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radi o-IdUrd and possibly other dThd analogues.