The preparation of clinical grade 5-[123I]iodo-2'-deoxyuridine and 5-[125I]iodo-2'-deoxyuridine with high in vitro stability and the potential for early proliferation scintigraphy.
METHODS
5-Iodo-2'-deoxyuridine (IdUrd) radiolabelled with the positron emitter I or with the gamma and Auger electron emitters I or I has been proposed for cancer diagnosis and therapy. We modified the synthesis to reliably obtain [I]IdUrd and [I]IdUrd by using an Iodogen supported destannylation reaction of 5-(tri-n-butylstannyl)-2'-deoxyuridine (Bu3SndUrd) which meets the requirements for good laboratory practice (GLP) and good clinical practice (GCP). A method of purification was developed to eliminate by-products as well as any unreacted starting material.


RESULTS
[I]IdUrd, which originated from a trace of iodide in the Bu3SndUrd precursor, was identified as the unknown by-product reported for this method. This trace could be eliminated by modified purification of Bu3SndUrd. Stabilization of pH was essential for unequivocal identification of radiolabelled IdUrd and possible degradation products in the different systems tested for quality control. Biodistribution in tumour bearing nude mice was measured as early as 3 and 6 h after i.v. injection of [I]IdUrd. This compound showed high and specific activity uptake in tumour and dividing tissues when combined with 5-fluoro-2'-deoxyuridine pre-treatment. Uptake was specifically inhibited by injection of excess thymidine.
Schaffland
Andreas O
AO
Service of Nuclear Medicine, University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. aoschaffland@yahoo.com
Delaloye
Angelika Bischof
AB
Kosinski
Marek
M
Dupertuis
Yves M
YM
Buchegger
Franz
F
D000818:Animals; D002455:Cell Division; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007065:Idoxuridine / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging / Q000379:methods; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D007065:Idoxuridine