Hyperpolarized magnetic resonance spectroscopy for assessing tumor hypoxia.
BACKGROUND
Hypoxic tumor cells are radioresistant, therefore, identification of hypoxia is crucial. Hyperpolarized magnetic resonance spectroscopy (HPMRS) allows real time measurements of the conversion of pyruvate to lactate, the final step of anaerobic energy production, and may thus allow non-invasive identification of hypoxia or treatment-induced changes in oxygenation. The aim of the study was to investigate the usefulness of HPMRS as a means to assess tumor hypoxia and its dynamics during intervention.


METHODS
C3H mammary carcinomas grown in CDF1 mice were used. To manipulate with tumor oxygenation, non-anaesthetized mice were gassed with air, 10% or 100% oxygen prior to administration of hyperpolarized [1-¹³C]pyruvate and HPMRS analysis. A direct assessment of tumor oxygen partial pressure (pO2) distributions were made using the Eppendorf oxygen electrode in a separate, but similarly treated, group of mice.


RESULTS
Even though breathing 100% oxygen improved tumor oxygenation as evidenced by pO2 measurements, the mean (with 1 S.E.) [1-¹³C]lactate/[1-¹³C]pyruvate ratio was unaffected by this intervention, being 34 (30-37) in mice breathing air and 37 (33-42) in mice breathing 100% oxygen. In contrast, and in accordance with pO2 measurements, a significant increase in the [1-¹³C]lactate/[1-¹³C]pyruvate ratio was seen in 10% oxygen-breathing mice with a ratio of 46 (42-50).


CONCLUSIONS
Although, no metabolic change was observed during 100% O2 breathing using HPMRS, the significant increase in the [1-¹³C]lactate/[1-¹³C]pyruvate ratio during 10% oxygen breathing suggests, that HPMRS can detect hypoxia-driven changes in the metabolic fate of pyruvate. To what extent and for what purposes HPMRS may best supplement or complement established techniques like hypoxia PET needs to be unraveled in future research.
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus C , Denmark.
Ane B
AB
Iversen
b Institute for Clinical Medicine, The MR Research Centre , Aarhus N , Denmark.
Steffen
S
Ringgaard
b Institute for Clinical Medicine, The MR Research Centre , Aarhus N , Denmark.
Christoffer
C
Laustsen
b Institute for Clinical Medicine, The MR Research Centre , Aarhus N , Denmark.
Hans
H
Stødkilde-Jørgensen
c Department of Oncology , Aarhus University Hospital , Aarhus C , Denmark.
Lise
L
Bentzen
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus C , Denmark.
Morten
M
Busk
a Department of Experimental Clinical Oncology , Aarhus University Hospital , Aarhus C , Denmark.
Michael R
MR
Horsman
D000280:Administration, Inhalation; D000818:Animals; D015687:Cell Hypoxia; D005260:Female; D019344:Lactic Acid / Q000097:blood; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism*; D019289:Pyruvic Acid / Q000097:blood
D019344:Lactic Acid; D019289:Pyruvic Acid; D010100:Oxygen