Abstract
Gradient-recalled echo magnetic resonance imaging (GRE MRI), which gives information on blood flow and oxygenation changes (Robinson SP, Howe FA, Griffiths JR 1995, Int J Radiat Oncol Biol Phys 33: 855), was used to observe the responses of six rodent tumour models to carbogen breathing. In one transplanted rat tumour, the Morris hepatoma 9618a, and a chemically induced rat tumour, the MNU-induced mammary adenocarcinoma, there were marked image intensity increases, similar to those previously observed in the rat GH3 prolactinoma. In contrast, the rat Walker carcinosarcoma showed no response. In two mouse tumours, the RIF-1 fibrosarcoma and the human xenograft HT29, carbogen breathing induced a transient fall in signal intensity that reversed spontaneously within a few minutes. The rat GH3 prolactinoma was xenografted into nude mice, and an increase in image intensity was found in response to carbogen, suggesting that any effects that carbogen may have had on the host were not significant determinants of the tumour response. The increases in GRE image intensity of the MNU, H9618a and GH3 tumours during carbogen breathing are consistent with increases in tumour oxygenation and blood flow, whereas the responses of the RIF-1 and HT29 tumours may be the result of a transient steal effect followed by homeostatic correction.
Highlights
We initially demonstrated the applicability of Gradient-recalled echo (GRE) imaging to the study of tumour physiology by showing that carbogen breathing induced dramatic increases of up to 100% in image intensity of transplanted GH3 prolactinomas (Robinson et al, 1995) and we MNU mammary carcinoma H9618a hepatoma Walker carcinosarcoma RIF-1 fibrosarcoma HT29 colon carcinoma GH3 prolactinoma
We report the response to carbogen breathing, observed by Gradient-recalled echo magnetic resonance imaging (GRE magnetic resonance imaging (MRI)), of six other tumour types and discuss these observations with respect to tumour physiology
Three transplanted murine tumour models were used, the RIF-I fibrosarcoma grown in the flanks of C3H mice (Twentyman et al, 1980), the HT29 colon carcinoma, a human xenograft grown in the flanks of nulnu mice (Kimball and Brattain, 1980) and the rat GH3 prolactinoma grown in nulnu mice
Summary
Primary mammary carcinomas were induced in female Ludwig Wistar rats by three injections (50 mg kg-') of N-methyl-Nnitrosourea (MNU) (Williams et al, 1981). To immobilize the animal during MRI, anaesthesia was induced with a single intraperitoneal (i.p.) injection of a combination of fentanyl citrate (0.315 mg ml-') plus fluanisone (10 mg ml-') (Hypnorm; Janssen Pharmaceutical Ltd), midazolam (5 mg ml-') (Hypnovel; Roche) and water (1:1:2), at a dose of 4 ml kg-' for the rats and 10 ml kg-1 for the mice. This anaesthetic mixture has been shown to have a minimal effect on tumour blood flow (Menke and Vaupel, 1988) and 3'P-MRS characteristics (Sansom and Wood, 1994).
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