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
AuthorRøe, Kathrine; Seierstad, Therese; Kristian, Alexandr; Mikalsen, Lars Tore G; Mælandsmo, Gunhild; van der Kogel, Albert; Ree, Anne Hansen; Olsen, Dag Rune
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.
Open Access-article, according to info at http://dx.doi.org/10.1593/neo.10484. No OA-info in the pdf-file.
CitationNeoplasia 12(2010) nr. 10 s. 818-825
The following license file are associated with this item: