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

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 ADTwas 47.1%higher than K trans ofCWR22 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. © 2010 Neoplasia Press, Inc.