Tumor targeting in vivo and metabolic fate of 5-[125I]Iodo-2'-Deoxyuridine following intratumoral injection in patients with colorectal cancer

Previous studies have demonstrated the tumor-targeting potential of radioiodinated 5-iodo-2'-deoxyuridine (IUdR) in experimental animal models following direct intratumoral or intracavitary administration. The aim of this study was to measure the tumor uptake and metabolic fate of 5-[I-125]iodo-2'-deoxyuridine (I-125]IUdR) in humans after a single intratumoral injection. Ten patients with colorectal cancer were injected intratumorally with [I-125]IUdR (0.24-3.9 MBq) during endoscopy 24 hr before ablative surgery. Blood and urine samples were collected up to 72 hr after [I-125]IUdR injection. Following resection, the radioactivity in the tumor and the surrounding tissues was measured in a gamma counter, and microautoradiography was performed on semi-thin tissue sections to assess localization of the radiopharmaceutical at the cellular level. An average of 0.234% of the injected dose was present per gram of tumor (range 0.009-0.918, median value 0.147), and tumor-to-nontumor radioactivity incorporation ratios were high for colonic mucosa when the nontumor tissue was taken at 1 cm (mean 629, range 27-2391) and 15 cm (mean 2387, range 122-12674) from the injection site. Microautoradiography confirmed these high tumor-to-nontumor ratios and demonstrated localization of [I-125]IUdR in the tumor cell nuclei. These results suggest that radioiodinated IUdR might have potential as a tumor-targeting agent in humans, provided homogeneous intratumoral distribution of the radiopharmaceutical by a suitable route of loco-regional administration can be achieved.