Estimation of tumor oxygenation and metabolic rate using 31P MRS: correlation of longitudinal relaxation with tumor growth rate and DNA synthesis.
31P MRS longitudinal relaxation times (T1) were determined for C3H murine fibrosarcomas (FSaII), and mammary carcinomas (MCaIV). Tumors were implanted in the foot dorsum, and were 100-300 mm3 in volume. T1s were repeated after the animal was allowed to breathe 100% oxygen for 30 min and then again 36-48 hr following 30 Gy. The spectrum were obtained using an 8.5 T spectrometer with a 8 cm bore and a 1.4 cm single turn antenna coil. The 31P relaxation times for untreated tumors in air breathing animals were: 3.78 sec for phosphomonoesters, 4.37 sec for inorganic phosphate (Pi), 2.73 sec for phosphocreatine, 1.37 sec for gamma ATP, 1.14 sec for alpha ATP, and 1.18 sec for beta ATP. The Pi T1s were 4.37 and 4.70 sec in control and irradiated tumors in air breathing animals. Respiration of oxygen for 30 min reduced the T1s to 3.02 and 2.62 sec in control and irradiated tumors respectively. The Pi T1 of an anoxic tumor, determined on an in situ tumor 60 min after death was 5.93 sec. The oxygen breathing induced decrease in the T1 of Pi is unlikely to have been caused by the paramagnetic properties of oxygen alone, and suggests a component of increased magnetization transfer secondary to the ATPase reaction. Oxygen breathing following 30 Gy, resulted in a decreased growth time (800 mm3 endpoint) and an increased proportion of cells in S-phase. These results support the hypothesis that the decrease in Pi T1 measured with oxygen breathing is a measure of tumor oxygen tension and metabolic rate, and suggests that T1 measurement may indirectly predict tumor growth rate and DNA synthesis.
Okunieff
P
P
Radiation Medicine Service, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Ramsay
J
J
Tokuhiro
T
T
Hitzig
B M
BM
Rummeny
E
E
McFarland
E
E
Neuringer
L J
LJ
Suit
H
H
D000818:Animals; D002588:Cesium Radioisotopes / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis* / Q000528:radiation effects; D005260:Female; D005354:Fibrosarcoma / Q000032:analysis / Q000378:metabolism* / Q000532:radiotherapy; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000378:metabolism* / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000032:analysis / Q000502:physiology / Q000528:radiation effects; D010101:Oxygen Consumption / Q000528:radiation effects; D010710:Phosphates / Q000032:analysis / Q000378:metabolism / Q000528:radiation effects; D010761:Phosphorus Radioisotopes; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D002588:Cesium Radioisotopes; D004273:DNA, Neoplasm; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D010100:Oxygen