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

被引:13
作者
Roe, Kathrine [1 ,2 ]
Seierstad, Therese [1 ,3 ]
Kristian, Alexandr [4 ]
Mikalsen, Lars Tore Gyland [2 ]
Maelandsmo, Gunhild Mari [4 ,5 ]
van der Kogel, Albert J. [6 ]
Ree, Anne Hansen [1 ,2 ]
Olsen, Dag Rune [7 ]
机构
[1] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Radiat Biol, N-0310 Oslo, Norway
[2] Univ Oslo, Oslo, Norway
[3] Buskerud Univ Coll, Fac Hlth Sci, Drammen, Norway
[4] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, N-0310 Oslo, Norway
[5] Univ Tromso, Fac Hlth Sci, Dept Pharm, Tromso, Norway
[6] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Radiat Oncol, NL-6525 ED Nijmegen, Netherlands
[7] Univ Bergen, Bergen, Norway
来源
NEOPLASIA | 2010年 / 12卷 / 10期
关键词
TUMOR XENOGRAFT; CANCER; HYPOXIA; CWR22; ANGIOGENESIS; CASTRATION; PARAMETERS; THERAPY; GROWTH; MODEL;
D O I
10.1593/neo.10484
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:818 / 825
页数:8
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