Abstract
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Objectives [18F]fluorothymidine ([18F]FLT) and [18F]fluoromethyluracil ([18F]FMAU) have been proposed as biomarkers of cell proliferation for PET imaging. We studied their uptake and relationships with proliferation on 2 prostatic cancer cell lines: MatLyLu (MLL) (hormone-independent) and LNCaP (hormone-dependent)
Methods Cell Uptake (CPM per million cells) of [3H]FLT and [3H]FMAU was compared to [3H]Thymidine (TdR) uptake (ß-counting). In order to vary the rate of proliferation, different cell growing conditions were tested, by varying the initial cell concentration (MLL) or adding various amounts of dihydrotestosterone (DHT) (LNCaP). Proliferation rates were estimated by cell counting, TdR incorporation and percentages of cells in S phase (flow-cytometer)
Results For MLL, the lowest and highest proliferation rates were observed with 700.000 and 100.000 cells/wells, respectively (S Phase: 8.51±1.9% to 20.5±0.7%). For LNCaP, the lowest and highest proliferation rates were observed without and with 10-7 M of DHT, respectively (S Phase: 3.38±1.33% to 7.58±1.06%). FMAU and FLT uptake rates increased dramatically with the MLL S phase (4 and 50 fold, respectively), and slightly with the LNCaP S phase, only for FLT (2 fold). There was no significant difference between FMAU LNCaP uptake with or without DHT. For MLL, uptake rates were higher for FLT than for FMAU, up to 14 % of TdR uptake. For LNCaP, uptake rates were higher for FMAU than for FLT, up to 59 % of TdR
Conclusions FMAU appears to be a less suitable biomarker of cell proliferation than FLT. However, its high human prostate cancer cell uptake could be of great interest for imaging prostate tumor and their bone marrow metastases (lower uptake in proliferating tissue than FLT)
- © 2009 by Society of Nuclear Medicine