Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation

Nobuyuki Oyama, Datta E. Ponde, Carmen Dence, Joonyoung Kim, Yuan Chuan Tai, Michael J. Welch

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77 Scopus citations

Abstract

3′-Deoxy-3′-18F-fluorothymidine (18F-FLT) has been recently described as a radiopharmaceutical for measuring cellular proliferation using PET imaging. Evaluation of tumor proliferative activity by PET using 18F-FLT could be a procedure to assess the viability of tumor, such as histologic grade, clinical stage, and prognosis as well as the early effects of cancer therapy. This study was undertaken to determine whether 18F-FLT is useful in the detection of prostate cancer as well as monitoring therapeutic effects in a human tumor model. Methods: The androgen-dependent human prostate tumor, CWR22, was implanted into athymic mice. This well-established model of prostate cancer was used in all studies. To determine the optimal imaging times for 18F-FLT, a biodistribution was performed in CWR22 mice. 18F-FLT (740 kBq [20 μCi]) was administered via the tail vein and uptake was determined in selected tissues at 5 min, 20 min, and 1, 2, and 4 h after injection (n = 5, each time point). Androgen ablation studies were conducted in the CWR22 model with either diethylstilbestrol (DES) or surgical castration. Animals received DES every 2 d for 3 wk. The effectiveness of therapy was monitored using 18F-FLT microPET as baseline, during treatment, and after treatment. Tracer accumulation in the tumor was then analyzed by comparing tumor-tomuscle ratios derived from reconstructed microPET data. Results: At 2 h after injection, the 18F-FLT uptake in tumor was 0.69 ± 0.14 percentage injected dose per gram of tissue, showing the highest activity of all organs measured. The microPET study with dynamic imaging showed that 18F-FLT uptake in blood reached its plateau within 1 min and was rapidly cleared, whereas 18F-FLT uptake in tumor reached its plateau in 30 min and remained up to 60 min. microPET using 18F-FLT successfully imaged the implanted CWR22 tumor in the mice at both 1 and 2 h after injection. There was a marked reduction of 18F-FLT uptake in tumor after castration or DES treatment; however, there were no differences in 18F-FLT uptake in the tumor in the control group. These changes of 18F-FLT uptake in tumor parallel the changes of actual tumor measurement. Conclusion: These results indicate that 18F-FLT is a useful tracer for detection of prostate cancer in an animal model. 18F-FLT has the potential for monitoring the therapeutic effect of androgen ablation therapy in prostate cancer.

Original languageEnglish
Pages (from-to)519-525
Number of pages7
JournalJournal of Nuclear Medicine
Volume45
Issue number3
StatePublished - Mar 1 2004

Keywords

  • 3′-deoxy-3′- F-fluorothymidine
  • PET
  • Prostate cancer
  • Tumor proliferation

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