title: Preclinical Auger and gamma radiation dosimetry for fluorodeoxyuridine-enhanced tumour proliferation scintigraphy with [123I]iododeoxyuridine.
abstract: Animal experiments have shown that short blocking of thymidine (dThd) synthesis with fluorodeoxyuridine (FdUrd) results in significantly increased DNA incorporation of [(125)I]iododeoxyuridine ([(125)I]IdUrd) in tumour and rapidly cycling tissues. Based on these results, we give an Auger and gamma radiation dosimetry estimate for a scintigraphy study in glioblastoma patients using [(123)I]IdUrd. The Auger radiation dosimetry calculated for patients is based on measurement of DNA-incorporated [(125)I]IdUrd in rapidly dividing tissues in nude mice xenografted with human glioblastoma. Further data obtained 0.5, 6 and 24 h after injection of [(125)I]IdUrd allowed calculation of the additional gamma radiation exposure using MIRDOSE3.1. High gradients of radioactivity concentration between dividing and non-dividing tissues were observed 6 and 24 h after injection of [(125)I]IdUrd combined with FdUrd pretreatment. While the estimated Auger radiation absorbed doses of [(123)I]IdUrd in six rapidly cycling normal tissues in patients are low, the equivalent doses become significant with application of the recommended preliminary radiation weighting factor (W(R)) of 20 for stochastic effects of DNA-associated Auger radiation. Using the latter W(R), extrapolation of the animal results to the proposed patient injection with 300 MBq [(123)I]IdUrd combined with FdUrd pretreatment indicates that the effective dose will be 5.42 mSv, including 1.67 mSv from Auger and 3.75 mSv from gamma radiation. The predicted Auger radiation effective dose for patients undergoing [(123)I]IdUrd scintigraphy will be significant if the enhancement of DNA incorporation that is achieved by means of FdUrd pretreatment is similar to that obtained in animals.
authors.affiliation: Division of Nuclear Medicine, University Hospital of Lausanne CHUV, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Franz.Buchegger@chuv.hospvd.ch
authors.forename: Franz
authors.initials: F
authors.lastname: Buchegger
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vieira
authors.forename: Peter
authors.initials: P
authors.lastname: Blaeuenstein
authors.forename: Yves Marc
authors.initials: YM
authors.lastname: Dupertuis
authors.forename: Andreas Oliver
authors.initials: AO
authors.lastname: Schaffland
authors.forename: Carine
authors.initials: C
authors.lastname: Grannavel
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Tribolet
authors.forename: Daniel Olivier
authors.initials: DO
authors.lastname: Slosman
authors.forename: Angelika
authors.initials: A
authors.lastname: Bischof Delaloye
mesh_terms: D000818:Animals; D001822:Body Burden; D003198:Computer Simulation; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004583:Electrons; D005467:Floxuridine / Q000008:administration & dosage*; D005720:Gamma Rays; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D019275:Radiopharmaceuticals; D005467:Floxuridine; D007065:Idoxuridine