Targeting tumors with iodine-123 labeled deoxyuridine: distribution and DNA binding.
5-lodo-2'-deoxyuridine (IUdR), a thymidine analog, is transported through cell membrane and is incorporated into newly synthesized DNA during the S phase of mitotic cells. In rapidly growing brain tumors such as glioma, radioiodinated IUdR may be an efficient diagnostic as well as therapeutic agent and may provide a means to determine the proliferative activity of the tumor. IUdR was labeled with 123I (t1/2 = 13.3 h, gamma = 159 KeV, 83%) and injected i.v. into nude mice bearing human colorectal carcinoma LS174T. At 3 and 20 h postinjection, tumor uptake was 2.6 +/- 0.9% and 0.5 +/- 0.2%, respectively, of the injected dose per gram of tissue. Radioactivity in other tissues also declined as a function of time, but much more rapidly, yielding tumor-to-blood ratios of 16.4 +/- 2.2 and tumor-to-muscle ratios of 22.2 +/- 7.7 at 20 h postinjection. Of the radioactivity in the tumor, 12.6 +/- 0.9% was bound to DNA at 3 h and 25.2 +/- 2% at 20 h postinjection. A high (7 +/- 1.1% i.d.) uptake in thyroid at 3 h postinjection indicated dehalogenation in vivo.
Thakur
M L
ML
Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Li
J
J
Kim
S M
SM
Zhang
J J
JJ
Andrews
D
D
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D007065:Idoxuridine