Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2'-deoxyuridine in patients with liver metastases from colorectal cancer.
We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2'-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer.


METHODS
Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/mumole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses.


RESULTS
In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues.


CONCLUSIONS
These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.
Mariani
G
G
CNR Institute of Clinical Physiology, University of Pisa, Italy.
Di Sacco
S
S
Volterrani
D
D
Di Luca
L
L
Buralli
S
S
Di Stefano
R
R
Baranowska-Kortylewicz
J
J
Bonora
D
D
Matteucci
F
F
Ricci
S
S
Bellina
C R
CR
Falcone
A
A
Salvadori
P A
PA
Mosca
F
F
Adelstein
S J
SJ
Kassis
A I
AI
D000368:Aged; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage
D007457:Iodine Radioisotopes; D007065:Idoxuridine