Antivascular effects of neoadjuvant androgen deprivation for prostate cancer: an in vivo human study using susceptibility and relaxivity dynamic MRI.
OBJECTIVE
The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy.


METHODS
Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K(trans)]), leakage space (v(e)) and blood oxygenation (intrinsic relaxivity [R(2)∗]) were calculated.


RESULTS
Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K(trans) and 53% for v(e) By 3 months, significant increases in R(2)∗ had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001).


CONCLUSIONS
Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R(2)∗ in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation.
Alonzi
Roberto
R
Marie Curie Research Wing, Mount Vernon Cancer Centre, Northwood, England. robertoalonzi@btinternet.com
Padhani
Anwar R
AR
Taylor
N Jane
NJ
Collins
David J
DJ
D'Arcy
James A
JA
Stirling
J James
JJ
Saunders
Michele I
MI
Hoskin
Peter J
PJ
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D001810:Blood Volume / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D015687:Cell Hypoxia / Q000502:physiology; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009570:Nitriles / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D012039:Regional Blood Flow / Q000187:drug effects; D015203:Reproducibility of Results; D013997:Time Factors; D014105:Tosyl Compounds / Q000627:therapeutic use
D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide; D010100:Oxygen