31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

Abstract

Summary The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, Ti 15 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and largevessel (non-nutritive) flow. All four tumour lines showed a decrease in fiNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg-' hydralazine i.v. was monitored by 31P-MRS. A marked decrease in f3NTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in PNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that earlygeneration transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

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“…This reduction in tumour perfusion results in nutrient and oxygen deprivation, and hence reduced bioenergetic status as observed in the 31 P MRS spectrum (an increase in P i relative to NTP). This has also been observed for hydralazine in other tumour models (Okunieff et al, 1988;Dunn et al, 1989;Bhujwalla et al, 1990;Robinson et al, 1998). SE MR images (Figure 1 C,D) are sensitive to flow, and hydralazine causes a decrease in overall signal intensity due to reduced perfusion.…”

“…βNTP/P i ratio) (Tozer and Griffiths, 1992). The combination of these MR methods was firstly validated in a pilot study following the response of GH3 prolactinomas to hydralazine, a vasodilator whose tumour vascular steal-effects are well documented (Jirtle, 1988;Robinson et al, 1998). Subsequently the tumour response to nicotinamide and carbogen was studied in vivo using MR and other complementary methods to elucidate the underlying mechanisms of action.…”

Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

“…Thanks to recent advances in imaging technology, powerful techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), have become widely available in clinic to demonstrate 2D and 3D highresolution images integrating both morphological and functional information. Furthermore, modern cell biology and molecular medicine have prompted miniaturization of these imaging modalities into micro-CT and MR micorscopy as nondestructive monitoring tools in life sciences for imaging small animals, such as mice [6,7,12,13]. However, all these dedicated equipments are extremely expensive and virtually unavailable to many clinic-based researchers, an obstacle that needs to be circumvented.…”

“…Most of the tumor models with allograft or xenograft implantation are preferentially made at subcutaneous locations due to the convenient operation and observation [3][4][5][6][7]. Subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) has been one of the most widely used mouse tumor models in cancer research for its biological stability, minimal immunogenicity, low metastatic potential, and responsiveness to various therapeutic interventions [8].…”

Challenges in Small Animal Noninvasive Imaging

“…The exceptions to this are inhaled superpolarized gases Viallon et al 1999) (lung volume imaging, perfusion imaging) and 2 H- (Ewy et al 1988;Robinson et al 1998) and 19 F-labeled fluorocarbon blood substitutes (Zimmermann et al 2000).…”