PT - JOURNAL ARTICLE AU - Agnieszka Morgenroth AU - Falk Schmidt AU - Sandra Deisenhofer AU - Boris Zlatopolskiy AU - Gerhard Glatting AU - Sven Reske TI - In vivo studies of a 5-[I-131/125]-iodo-4'-thio-2'-deoxyuridine in a HL60-xenograft mouse model: Effects of the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine DP - 2007 May 01 TA - Journal of Nuclear Medicine PG - 135P--135P VI - 48 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/48/supplement_2/135P.2.short 4100 - http://jnm.snmjournals.org/content/48/supplement_2/135P.2.full SO - J Nucl Med2007 May 01; 48 AB - 459 Objectives: The application of radiolabeled 5-iodo nucleoside analogues as proliferation marker is limited by their rapid in vivo degradation. As one major deactivation pathway the deiodination catalyzed by thymidylate synthase (TS), an essential enzyme for de novo synthesis of thymidylate und subsequently DNA synthesis, was identified. Our goal was to increase the stability towards TS deactivation and to study the biodistribution of 5-[I-131/125]-iodo-4'-thio-2'-deoxyuridine ([I-131/125]ITdU) in presence of FdU as TS-inhibitor in a HL60-xenograft mouse model. Methods: For biodistribution experiments with [I-131/125]ITdU three groups of scid mice bearing subcutaneous HL60-xenografts received pre-treatment with i.v. injections of different dose of FdU (2, 5 or 10 mg/kg total dose) 30 min prior to radio-ITdU injection. Tumor and normal organ tissues were dissected 30 min post radio-injection and uptake of [I-131]ITdU (%ID/g tissue) by organ and tumor tissue was determinded. Cellular distribution of [I-125]ITdU was imaged by microautoradiography. Expression of the proliferation markers TS and Ki67 were determined by immunohistological staining using corresponding paraffin sections of tumor and normal tissues. Results: The biodistribution studies demonstrated significant increased uptake of [I-131/125]ITdU in spleen, small intestine and tumor 30 min post injection in animals with FdU pre-treatment (highest accumulation of [I-131/125]ITdU with 10 mg/kg dose of FdU: spleen 69,8 ± 45,5 %ID/g, small intestine 7,4 ± 1,8 %ID/g and tumor 11,8 ± 1,8 %ID/g; non pre-treated group: spleen 5,0 ± 1,3 %ID/g, small intestine 3,3 ± 1,1 %ID/g, tumor 4,6 ± 1,2 %ID/g). The biodistribution results were additionally confirmed by microautoradiography. The immunohistological TS and Ki67 expression analysis demonstrated clearly correlation between uptake of [I-131/125]ITdU and proliferation state of cells. Conclusions: Pre-treatment with FdU efficiently inhibited deactivation of [I-131/125]ITdU by TS and led to high selective ITdU uptake in proliferating tumor cells. Research Support (if any): Supported by KFD 120, Teilprojekt P3 from DFG.