Early response assessment in prostate carcinoma by ¹⁸F-fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models.
OBJECTIVE
The aim of the study was to assess the potential usefulness of 3-deoxy-3-(18)F-fluorothymidine (FLT) as a radiopharmaceutical for imaging the early therapeutic effects of docetaxel (DTX) on tumour proliferation in hormone-refractory prostate cancer (HRPC).


METHODS
Cells of the androgen-independent human prostate tumour cell line, 22Rv1, were implanted in athymic male mice. Approximately 3 weeks after cell implantation, the mice were treated with DTX or vehicle. Before and after the treatment, the mice were imaged with a microPET-Focus-F120 scanner (Concorde Microsystems, Knoxville, TN, USA) using FLT and (18)F-fluorodeoxyglucose (FDG). Tracer accumulations in the tumours were then analysed and compared with the proliferation activity and apoptotic index of the tumours. In a separate cell study, 22Rv1 cells were treated with DTX, then incubated with FLT or FDG and examined for their tracer uptake.


RESULTS
The microPET imaging showed a significant decrease of FLT uptake in tumours after administration of DTX, while the changes of FDG uptake were minimal. Immunohistochemical analysis of the tumours revealed that the changes of FLT uptake were well correlated with those of proliferation activity but not with the apoptotic index. In vitro studies demonstrated that the significant decrease of FLT uptake in the cells after incubation with DTX correlated with the % S-phase cell fraction, while there were only minimal changes in the prostate-specific antigen concentration of the cell medium and FDG uptake in the cells.


CONCLUSIONS
These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC.
Oyama
Nobuyuki
N
Department of Urology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Fukui, 9101193, Japan. urono@u-fukui.ac.jp
Hasegawa
Yoko
Y
Kiyono
Yasushi
Y
Kobayashi
Masato
M
Fujibayashi
Yasuhisa
Y
Ponde
Datta E
DE
Dence
Carmen
C
Welch
Michael J
MJ
Yokoyama
Osamu
O
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015224:Dideoxynucleosides / Q000378:metabolism; D004195:Disease Models, Animal; D000077143:Docetaxel; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D043823:Taxoids; D000077143:Docetaxel; C002854:alovudine