Longitudinal magnetic resonance imaging-based assessment of vascular changes and radiation response in androgen-sensitive prostate carcinoma xenografts under androgen-exposed and androgen-deprived conditions

Neoplasia. 2010 Oct;12(10):818-25. doi: 10.1593/neo.10484.

Abstract

Prostate cancer (PCa) patients receive androgen-deprivation therapy (ADT) to reduce tumor burden. However, complete eradication of PCa is unusual, and recurrent disease is evident within approximately 2 years in high-risk patients. Clinical evidence suggests that combining ADT with radiotherapy improves local control and disease-free survival in these patients compared with radiotherapy alone. We investigated whether vascularization of androgen-sensitive PCa xenografts changed after ADT and whether such therapy affected radiation response. CWR22 xenografts received combinations of ADT by castration (CWR22-cas) and 15 Gy of single-dose irradiation. At a shortest tumor diameter of 8 mm, vascularization was visualized by dynamic contrast-enhanced magnetic resonance imaging before radiation and 1 and 9 days after radiation. Voxel-wise quantitative modeling of contrast enhancement curves extracted the hemodynamic parameter K(trans), reflecting a combination of permeability, density, and blood flow. Tumor volumes and prostate-specific antigen (PSA) were monitored during the experiment. The results showed that K(trans) of CWR22-cas tumors 36±4 days after ADT was 47.1% higher than K(trans) of CWR22 tumors (P = .01). CWR22-cas tumors showed no significant changes in K(trans) after radiation, whereas K(trans) of CWR22 tumors at day 1 decreased compared with pretreatment values (P = .04) before a continuous increase from day 1 to day 9 followed (P = .01). Total PSA in blood correlated positively to tumor volume (r = 0.59, P < .01). In conclusion, androgen-exposed xenografts demonstrated radiation-induced reductions in vascularization and tumor volumes, whereas androgen-deprived xenografts showed increased vascularization and growth inhibition, but no significant additive effect of radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Castration
  • Cobalt Radioisotopes / therapeutic use
  • Combined Modality Therapy
  • Humans
  • Immunoenzyme Techniques
  • Magnetic Resonance Imaging*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Hormone-Dependent / blood supply*
  • Neoplasms, Hormone-Dependent / radiotherapy
  • Neoplasms, Hormone-Dependent / surgery
  • Neoplasms, Hormone-Dependent / therapy*
  • Neovascularization, Pathologic / diagnosis*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood supply*
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / therapy*
  • Survival Rate
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Androgens
  • Cobalt Radioisotopes
  • Prostate-Specific Antigen