Abstract
| Language | English |
|---|---|
| Article number | 05 |
| Pages | 44-52 |
| Number of pages | 9 |
| Journal | Journal of Cancer Therapy |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 8 Jan 2014 |
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Keywords
- L-NNA
- nitric oxide
- perfusion
- vascular
- imaging
- cancer
Cite this
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The acute physiological effects of the vaso-active drug, L-NNA, a nitric oxide synthase inhibitor, on renal and tumour perfusion in human subjects. / Yip, Kent; Goh, Vicky; Gregory, Jane; Simcock, Ian; Stirling, J. James; Taylor, N. Jane; Kozarski, Robert; Mitchell, Andrew; Bosopem, Sam; Halbert, Gavin; Alonzi, Roberto; Miles, David; Hoskin, Peter.
In: Journal of Cancer Therapy, Vol. 5, No. 1, 05, 08.01.2014, p. 44-52.Research output: Contribution to journal › Article
TY - JOUR
T1 - The acute physiological effects of the vaso-active drug, L-NNA, a nitric oxide synthase inhibitor, on renal and tumour perfusion in human subjects
AU - Yip, Kent
AU - Goh, Vicky
AU - Gregory, Jane
AU - Simcock, Ian
AU - Stirling, J. James
AU - Taylor, N. Jane
AU - Kozarski, Robert
AU - Mitchell, Andrew
AU - Bosopem, Sam
AU - Halbert, Gavin
AU - Alonzi, Roberto
AU - Miles, David
AU - Hoskin, Peter
PY - 2014/1/8
Y1 - 2014/1/8
N2 - To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selec-tive inhibitor of nitric oxide synthase, L-NNA. Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood vo-lume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%; renal BV— 19.7%; tumour BF—16.9%; tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tu-mour within 1 hour following L-NNA (p < 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.
AB - To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selec-tive inhibitor of nitric oxide synthase, L-NNA. Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood vo-lume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%; renal BV— 19.7%; tumour BF—16.9%; tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tu-mour within 1 hour following L-NNA (p < 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.
KW - L-NNA
KW - nitric oxide
KW - perfusion
KW - vascular
KW - imaging
KW - cancer
U2 - 10.4236/jct.2014.51006
DO - 10.4236/jct.2014.51006
M3 - Article
VL - 5
SP - 44
EP - 52
JO - Journal of Cancer Therapy
T2 - Journal of Cancer Therapy
JF - Journal of Cancer Therapy
SN - 2151-1934
IS - 1
M1 - 05
ER -