3′-Deoxy-3′-[18F]Fluorothymidine Uptake Is Related to Thymidine Phosphorylase Expression in Various Experimental Tumor Models

• Published in: Molecular imaging and biology Vol. 20; no. 2; pp. 194 - 199
• Main Authors: Schelhaas, Sonja, Heinzmann, Kathrin, Honess, Davina J., Smith, Donna-Michelle, Keen, Heather, Heskamp, Sandra, Witney, Timothy H., Besret, Laurent, Doblas, Sabrina, Griffiths, John R., Aboagye, Eric O., Jacobs, Andreas H.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2018; Springer Nature B.V
• Subjects: Animals; Brief Article; Dideoxynucleosides - chemistry; Dideoxynucleosides - pharmacokinetics; Emission measurements; Fluorine isotopes; Humans; Imaging; Lung cancer; Lysates; Medicine; Medicine & Public Health; Mice; Neoplasms, Experimental - enzymology; Phosphorylase; Positron emission; Positron emission tomography; Radiology; Thymidine; Thymidine - metabolism; Thymidine phosphorylase; Thymidine Phosphorylase - metabolism; Thymidylate synthase; Tomography; Tumors; Western blotting; Xenografts; Xenotransplantation; Oncology; F]FLT; [; PET; Thymidine phosphorylase; [18F]FLT
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-017-1125-3

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 SUV max ( 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.