18F-FLT and 125I-IdUrd uptake increase in human tumour cell lines induced by the thymidylate synthase inhibitor FdUrd

Autor:	Tobias Ludwig Ross, David Viertl, Pierre-Alain André, Florence Perillo-Adamer, A. Bischof Delaloye, Marek Kosinski, Simon M. Ametamey, F. Buchegger, Yves M. Dupertuis
Rok vydání:	2012
Předmět:	Cell Spheroid Endogeny General Medicine Molecular biology In vitro Basal (phylogenetics) chemistry.chemical_compound medicine.anatomical_structure chemistry Cell culture embryonic structures cardiovascular system medicine Radiology Nuclear Medicine and imaging Thymidine Nucleotide salvage
Zdroj:	Nuklearmedizin. 51:163-169
ISSN:	2567-6407 0029-5566
DOI:	10.3413/nukmed-0459-12-01
Popis:	Summary Aim: 5-fluoro-2′-deoxyuridine (FdUrd) depletes the endogenous 5′-deoxythymidine triphosphate (dTTP) pool. We hypothesized whether uptake of exogenous dThd analogues could be favoured through a feedback enhanced salvage pathway and studied the FdUrd effect on cellular uptake of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and 5-125I-iodo-2′-deoxyuridine (125I-IdUrd) in different cancer cell lines in parallel. Methods: Cell uptake of 18F-FLT and 125I-IdUrd was studied in 2 human breast, 2 colon cancer and 2 glioblastoma lines. Cells were incubated with/without 1 μmol/l FdUrd for 1 h and, after washing, with 1.2 MBq 18F-FLT or 125I-IdUrd for 0.3 to 2 h. Cell bound 18F-FLT and 125I-IdUrd was counted and expressed in % incubated activity (%IA). Kinetics of 18F-FLT cell uptake and release were studied with/without FdUrd modulation. 2′-3H-methyl-fluorothymidine (2′-3H-FLT) uptake with/without FdUrd pretreatment was tested on U87 spheroids and monolayer cells. Results: Basal uptake at 2 h of 18F-FLT and 125I-IdUrd was in the range of 0.8–1.0 and 0.4–0.6 Bq/cell, respectively. FdUrd pretreatment enhanced 18F-FLT and 125I-IdUrd uptake 1.2–2.1 and 1.7–4.4 fold, respectively, while co-incubation with excess thymidine abrogated all 18F-FLT uptake. FdUrd enhanced 18F-FLT cellular inflow in 2 breast cancer lines by factors of 1.8 and 1.6, respectively, while outflow persisted at a slightly lower rate. 2′-3H-FLT basal uptake was very low while uptake increase after FdUrd was similar in U87 monolayer cells and spheroids. Conclusions: Basal uptake of 18F-FLT was frequently higher than that of 125I-IdUrd but FdUrd induced uptake enhancement was stronger for 125I-IdUrd in five of six cell lines. 18F-FLT outflow from cells might be an explanation for the observed difference with 125I-IdUrd.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::194127ef3e2ba3d3138848d7c9c4834d https://doi.org/10.3413/nukmed-0459-12-01 Zobrazit plný text záznamu