Comparison of the effects of hydralazine on tumor and normal tissue blood perfusion by MRI

Belfi, Charles A.; Paul, Chitta R.; Shan, Siqing; Ngo, Frank Q.H.

doi:10.1016/0360-3016(94)90441-3

Cited by 19 publications

(13 citation statements)

References 17 publications

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“…Hydralazine slowed down the signal enhancement decay rate in the liver, muscle, and tumor probably because decreased blood flow to the kidney resulted in decreased clearance of Gd-DTPA from the bloodstream. Belfi et al (27,28) also used a similar MRI technique in a mouse KHT sarcoma tumor model and reported similar results to those reported here. They noted that the initial upslope in signal enhancement was greatly reduced in the tumor and that clearance was slowed down.…”

Section: Hydralazine Studysupporting

confidence: 91%

Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd‐DTPA‐enhanced MRI

Wang

Roth

et al. 1996

Magnetic Resonance in Med

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The effects of three physiologically different vasomodulators, angiotensin II (a vasoconstrictor), hydralazine (a vasodilator), and histamine (a permeability modulator), on the pharmaco-kinetics of entry of small molecules (measured by Gd-DTPA concentration) into normal and abnormal tissue were studied in rats implanted with R3230 AC tumors. Sequential dynamic Gd-DTPA-enhanced MRI studies, one before and one after vasomodulator administration, were performed, and the signal intensities of various tissues analyzed. Angiotensin II (6 micrograms/kg) reduced blood flow in tumors, but increased it in muscles. Hydralazine (5 mg/kg) reduced blood flow in tumors, kidneys, and livers, and slowed Gd-DTPA clearance from tumors, livers, and muscles. Histamine (25 micrograms/kg) increased renal blood flow, hastening Gd-DTPA clearance causing reduced measurable blood flow in tumors and muscles. By simultaneously monitoring the effects in various tissues, the pharmacokinetic effect of each drug in the entire body could be obtained.

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Section: Hydralazine Studysupporting

confidence: 91%

Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd‐DTPA‐enhanced MRI

Wang

Roth

et al. 1996

Magnetic Resonance in Med

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“…Paramagnetic contrast agents containing gadolinium have also been used to estimate perfusion, permeability, and/or vascular volume using dynamic 1 H MRI. [14][15][16][17][18][19][20][21][22][23] Unlike water, these agents normally do not cross the plasma membrane and remain in intravascular and interstitial spaces. Owing to the presence of chaotic and leaky vessels in a tumor, Gd-DTPA kinetics may depend on both perfusion and vascular permeability, making it difficult to separate the two parameters.…”

Section: Introductionmentioning

confidence: 99%

Detecting early response to cyclophosphamide treatment of RIF‐1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging

et al. 2003

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The purpose of this study was to develop a reliable, noninvasive method for early detection of tumor response to therapy that would facilitate optimization of treatment regimens to the needs of the individual patient. In the present study, the effects of cyclophosphamide (Cp, a widely used alkylating agent) were monitored in a murine radiation induced fibrosarcoma (RIF-1) using in vivo (1)H NMR spectroscopy and imaging to evaluate the potential of these techniques towards early detection of treatment response. Steady-state lactate levels and Gd-DTPA uptake kinetics were measured using selective multiple quantum coherence (Sel-MQC) transfer spectroscopy and dynamic contrast enhanced imaging, respectively in RIF-1 tumors before, 24 and 72 h after 300 mg/kg of Cp administration. High-resolution (1)H NMR spectra of perchloric acid extracts of the tumor were correlated with lactate and glucose concentrations determined enzymatically. In vivo NMR experiments showed a decrease in steady-state lactate to water ratios (5.4 +/- 1.6 to 0.6 +/- 0.5, p < 0.05) and an increase in Gd-DTPA uptake kinetics following treatment response. The data indicate that decreases in lactate result from decreased glycolytic metabolism and an increase in tumor perfusion/permeability. Perchloric acid extracts confirmed the lower lactate levels seen in vivo in treated tumors and also indicated a higher glycerophosphocholine/phosphocholine (GPC/PC) integrated intensity ratio (1.39 +/- 0.09 vs 0.97 +/- 0.04, p < 0.01), indicative of increased membrane degradation following Cp treatment. Steady-state lactate levels provide metabolic information that correlates with changes in tumor physiology measured by Gd-DTPA uptake kinetics with high spatial and temporal resolution. Both of these parameters may be useful for monitoring early tumor response to therapy.

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“…The tumor vasculature of subcutaneously or intramuscularly implanted rodent tumors in flank or hindlimb is mostly parallel to the host tissue vasculature (7). Vasodilator agents, such as hydralazine and nitroglycerin, were found to decrease the blood perfusion in such rodent tumors as measured by 1 H-MRI studies of the Gd-DTPA uptake (15,34) and by laser Doppler flow studies (9). Simultaneously hydralazine was found to increase blood perfusion in muscle tissue (15,34).…”

Section: Discussionmentioning

confidence: 99%

Effect of carbogen breathing on the physiological profile of human glioma xenografts

et al. 1999

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Comparison of the effects of hydralazine on tumor and normal tissue blood perfusion by MRI

Cited by 19 publications

References 17 publications

Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd‐DTPA‐enhanced MRI

Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd‐DTPA‐enhanced MRI

Detecting early response to cyclophosphamide treatment of RIF‐1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging

Effect of carbogen breathing on the physiological profile of human glioma xenografts

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