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Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Clinical Cancer Research, 12, 2006, 10, S. 3115-3123 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. |
|---|---|
| author |
Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. |
| spellingShingle |
Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. Clinical Cancer Research Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients Cancer Research Oncology |
| author_sort |
gupta, nishi |
| spelling |
Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-05-0513 <jats:title>Abstract</jats:title> <jats:p>Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.</jats:p> <jats:p>Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered.</jats:p> <jats:p>Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention.</jats:p> <jats:p>Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.</jats:p> Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients Clinical Cancer Research |
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American Association for Cancer Research (AACR), 2006 |
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American Association for Cancer Research (AACR), 2006 |
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1078-0432 1557-3265 |
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| title |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_unstemmed |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_full |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_fullStr |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_full_unstemmed |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_short |
Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_sort |
carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-05-0513 |
| publishDate |
2006 |
| physical |
3115-3123 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.</jats:p>
<jats:p>Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered.</jats:p>
<jats:p>Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention.</jats:p>
<jats:p>Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.</jats:p> |
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| author | Gupta, Nishi, Saleem, Azeem, Kötz, Barbara, Osman, Safiye, Aboagye, Eric O., Phillips, Robert, Vernon, Clare, Wasan, Harpreet, Jones, Terry, Hoskin, Peter J., Price, Patricia M. |
| author_facet | Gupta, Nishi, Saleem, Azeem, Kötz, Barbara, Osman, Safiye, Aboagye, Eric O., Phillips, Robert, Vernon, Clare, Wasan, Harpreet, Jones, Terry, Hoskin, Peter J., Price, Patricia M., Gupta, Nishi, Saleem, Azeem, Kötz, Barbara, Osman, Safiye, Aboagye, Eric O., Phillips, Robert, Vernon, Clare, Wasan, Harpreet, Jones, Terry, Hoskin, Peter J., Price, Patricia M. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.</jats:p> <jats:p>Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered.</jats:p> <jats:p>Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention.</jats:p> <jats:p>Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.</jats:p> |
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| imprint | American Association for Cancer Research (AACR), 2006 |
| imprint_str_mv | American Association for Cancer Research (AACR), 2006 |
| institution | DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Rs1, DE-Pl11, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3 |
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| spelling | Gupta, Nishi Saleem, Azeem Kötz, Barbara Osman, Safiye Aboagye, Eric O. Phillips, Robert Vernon, Clare Wasan, Harpreet Jones, Terry Hoskin, Peter J. Price, Patricia M. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-05-0513 <jats:title>Abstract</jats:title> <jats:p>Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.</jats:p> <jats:p>Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered.</jats:p> <jats:p>Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention.</jats:p> <jats:p>Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.</jats:p> Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients Clinical Cancer Research |
| spellingShingle | Gupta, Nishi, Saleem, Azeem, Kötz, Barbara, Osman, Safiye, Aboagye, Eric O., Phillips, Robert, Vernon, Clare, Wasan, Harpreet, Jones, Terry, Hoskin, Peter J., Price, Patricia M., Clinical Cancer Research, Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients, Cancer Research, Oncology |
| title | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_full | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_fullStr | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_full_unstemmed | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_short | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| title_sort | carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients |
| title_unstemmed | Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-05-0513 |