title: The effects of tumour blood flow and oxygenation modifiers on subcutaneous tumours as determined by NIRS.
abstract: Modulation of tumour oxygenation may be used to increase or decrease tumour hypoxia in order to improve the effect of radiotherapy or bioreductive drugs, respectively. Magnetic resonance imaging (MRI) and near infrared spectroscopy (NIRS) are techniques sensitive to blood deoxyhemoglobin concentration (Hb) that can be used to investigate tumour hypoxia indirectly via blood oxygenation levels. In this study we have used NIRS to determine absolute Hb and changes in deoxyhemoglobin and oxyhemoglobin (HbO) in subcutaneous rodent tumours for challenges that alter blood flow and oxygenation, with the aim to better interpret our MRI data. Both carbogen [95% O2 + 5% CO2] and 100% O2 breathing produced a similar and significant reduction in Hb and increase in HbO, but a negligible change in HbT (= Hb + HbO). In contrast, N2 breathing to terminal anoxia and intravenous hydralazine produced a negligible increase in Hb, but large reductions in HbO and HbT. HbT is proportional to blood volume, so our data suggests large blood volume decreases occur with challenges likely to cause reduced arterial blood pressure. Hence MRI techniques that measure the R2* relaxation rate, which varies linearly with total Hb, will underestimate the effects of hypotensive agents at increasing tumour hypoxia.
authors.forename: Franklyn A
authors.initials: FA
authors.lastname: Howe
authors.forename: James P
authors.initials: JP
authors.lastname: Connelly
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
authors.forename: Roger
authors.initials: R
authors.lastname: Springett
authors.forename: John R
authors.initials: JR
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D018496:Hyperoxia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000097:blood* / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000097:blood* / Q000098:blood supply* / Q000188:drug therapy / Q000532:radiotherapy; D015175:Prolactinoma / Q000097:blood* / Q000098:blood supply* / Q000188:drug therapy / Q000532:radiotherapy; D011836:Radiation Tolerance; D051381:Rats; D011920:Rats, Inbred WF; D012039:Regional Blood Flow; D019265:Spectroscopy, Near-Infrared
chemical_list: D006454:Hemoglobins; D010108:Oxyhemoglobins; D002245:Carbon Dioxide; D006830:Hydralazine; C011700:carbogen; C100003:deoxyhemoglobin; D010100:Oxygen