TY - JOUR
T1 - Tumor oxygen dynamics
T2 - Correlation of in vivo MRI with histological findings
AU - Zhao, Dawen
AU - Ran, Sophia
AU - Constantinescu, Anca
AU - Hahn, Eric W.
AU - Mason, Ralph P.
N1 - Funding Information:
Abbreviations: EPI, echo planar imaging; FREDOM, Fluorocarbon Relaxometry Using Echo Planar Imaging for Dynamic Oxygen Mapping; HF, hypoxic fraction; HFB, hexafluorobenzene; VDT, volume doubling time Address all correspondence to: Ralph P. Mason, PhD, C Chem, Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9058, USA. E-mail: ralph.mason@utsouthwestern.edu 1This research was supported, in part, by NIH RO1 CA79515 (NCI)/EB002762 (NIBIB) and the DOD Prostate Cancer Initiative Postdoctoral Award (DAMD 170110108) (D.Z.), and performed in conjunction with Cancer Imaging Program P20 CA 86354. Received 23 January 2003; Accepted 25 April 2003.
PY - 2003
Y1 - 2003
N2 - Tumor oxygenation has long been recognized as a significant factor influencing cancer therapy. We recently established a novel magnetic resonance in vivo approach to measuring regional tumor oxygen tension, FREDOM (Fluorocarbon Relaxometry Using Echo Planar Imaging for Dynamic Oxygen Mapping), using hexafluorobenzene (HFB) as the reporter molecule. We have now investigated oxygen dynamics in the two Dunning prostate R3327 rat tumor sublines, AT1 and H. FREDOM revealed considerable intratumoral heterogeneity in the distribution of pO2 values in both sublines. The anaplastic faster-growing AT1 tumors were more hypoxic compared with the size-matched, well-differentiated, and slower-growing H tumors. Respiratory challenge with oxygen produced significant increases in mean and median pO2 in all the H tumors (P<.001), but no response in half of the larger AT1 tumors (>3 cm3). Immunohistochemical studies using the hypoxia marker, pimonidazole, and the vascular endothelial cell marker, CD31, confirmed that the H tumors had more extensive vasculature and less hypoxia than the AT1 tumors. These results further validate the utilization of FREDOM to monitor tumor oxygenation and concur with the hypothesis that the level of hypoxia is related to tumor growth rate and poor vascularity.
AB - Tumor oxygenation has long been recognized as a significant factor influencing cancer therapy. We recently established a novel magnetic resonance in vivo approach to measuring regional tumor oxygen tension, FREDOM (Fluorocarbon Relaxometry Using Echo Planar Imaging for Dynamic Oxygen Mapping), using hexafluorobenzene (HFB) as the reporter molecule. We have now investigated oxygen dynamics in the two Dunning prostate R3327 rat tumor sublines, AT1 and H. FREDOM revealed considerable intratumoral heterogeneity in the distribution of pO2 values in both sublines. The anaplastic faster-growing AT1 tumors were more hypoxic compared with the size-matched, well-differentiated, and slower-growing H tumors. Respiratory challenge with oxygen produced significant increases in mean and median pO2 in all the H tumors (P<.001), but no response in half of the larger AT1 tumors (>3 cm3). Immunohistochemical studies using the hypoxia marker, pimonidazole, and the vascular endothelial cell marker, CD31, confirmed that the H tumors had more extensive vasculature and less hypoxia than the AT1 tumors. These results further validate the utilization of FREDOM to monitor tumor oxygenation and concur with the hypothesis that the level of hypoxia is related to tumor growth rate and poor vascularity.
KW - F nuclear magnetic resonance (NMR)
KW - Hypoxia
KW - Immunohistochemistry
KW - Oxygen tension
KW - Prostate tumor
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U2 - 10.1016/s1476-5586(03)80024-6
DO - 10.1016/s1476-5586(03)80024-6
M3 - Article
C2 - 14511402
AN - SCOPUS:0041854257
SN - 1522-8002
VL - 5
SP - 308
EP - 318
JO - Neoplasia
JF - Neoplasia
IS - 4
ER -