Schelhaas, S; Heinzmann, K; Honess, DJ; Smith, D-M; Keen, H; Heskamp, S; Witney, TH; ... Jacobs, AH; + view all Schelhaas, S; Heinzmann, K; Honess, DJ; Smith, D-M; Keen, H; Heskamp, S; Witney, TH; Besret, L; Doblas, S; Griffiths, JR; Aboagye, EO; Jacobs, AH; - view fewer (2018) 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models. Molecular Imaging and Biology , 20 (2) pp. 194-199. 10.1007/s11307-017-1125-3.

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Abstract

PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [(18)F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [(18)F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001). CONCLUSIONS: In a broad range of tumors, [(18)F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [(18)F]FLT uptake.

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