Monitoring the effects of anti-angiogenesis on the radiation sensitivity of pancreatic cancer xenografts using dynamic contrast-enhanced computed tomography

Ning Cao, Minsong Cao, Helen Chin-Sinex, Marc Mendonca, Song Chu Ko, Keith M. Stantz

Research output: Contribution to journalArticle

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Abstract

Purpose To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy. Methods and Materials Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors. Results Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤.01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15%) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio. Conclusions DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response.

Original languageEnglish
Pages (from-to)412-418
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume88
Issue number2
DOIs
StatePublished - Feb 1 2014

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angiogenesis
Radiation Tolerance
Pancreatic Neoplasms
Heterografts
tumors
tomography
cancer
Tomography
radiation therapy
Radiotherapy
radiation
Neoplasms
Perfusion
dosage
Radiation Dosage
therapy
Plasma Volume
Growth
Blood Vessels
mice

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Monitoring the effects of anti-angiogenesis on the radiation sensitivity of pancreatic cancer xenografts using dynamic contrast-enhanced computed tomography. / Cao, Ning; Cao, Minsong; Chin-Sinex, Helen; Mendonca, Marc; Ko, Song Chu; Stantz, Keith M.

In: International Journal of Radiation Oncology Biology Physics, Vol. 88, No. 2, 01.02.2014, p. 412-418.

Research output: Contribution to journalArticle

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abstract = "Purpose To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy. Methods and Materials Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors. Results Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤.01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15{\%}) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio. Conclusions DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response.",
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AU - Cao, Minsong

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AU - Mendonca, Marc

AU - Ko, Song Chu

AU - Stantz, Keith M.

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N2 - Purpose To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy. Methods and Materials Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors. Results Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤.01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15%) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio. Conclusions DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response.

AB - Purpose To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy. Methods and Materials Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors. Results Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤.01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15%) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio. Conclusions DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response.

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