In Vivo Near-Infrared Spectroscopy and Magnetic Resonance Imaging Monitoring of Tumor Response to Combretastatin A-4-Phosphate Correlated With Therapeutic Outcome

Journal Article · Wed Jun 01 04:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.12.028· OSTI ID:21491762

Chenghui, Chang ^[1]; Kim, Jae G; Hanli, Liu ^[2]; Mason, Ralph P ^[3]

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1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)
2. Joint Program in Biomedical Engineering, University of Texas Arlington and University of Texas Southwestern Medical Center, Arlington, Texas (United States)
3. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

Purpose: To develop a combination treatment consisting of combretastatin A-4-phosphate (CA4P) with radiation based on tumor oxygenation status. Methods and Materials: In vivo near-infrared spectroscopy (NIRS) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were applied to noninvasively monitor changes in tumor blood oxygenation and necrosis induced by CA4P (30 mg/kg) in rat mammary 13762NF adenocarcinoma, and the evidence was used to optimize combinations of CA4P and radiation treatment (a single dose of 5 Gy). Results: NIRS showed decreasing concentrations of tumor vascular oxyhemoglobin and total hemoglobin during the first 2 h after CA4P treatment, indicating significant reductions in tumor blood oxygenation and perfusion levels (p < 0.001). Twenty-four hours later, in response to oxygen inhalation, significant recovery was observed in tumor vascular and tissue oxygenation according to NIRS and pimonidazole staining results, respectively (p < 0.05). DW MRI revealed significantly increased water diffusion in tumors measured by apparent diffusion coefficient at 24 h (p < 0.05), suggesting that CA4P-induced central necrosis. In concordance with the observed tumor oxygen dynamics, we found that treatment efficacy depended on the timing of the combined therapy. The most significant delay in tumor growth was seen in the group of tumors treated with radiation while the rats breathed oxygen 24 h after CA4P administration. Conclusions: Noninvasive evaluation of tumor oxygen dynamics allowed us to rationally enhance the response of syngeneic rat breast tumors to combined treatment of CA4P with radiation.

• OSTI ID: 21491762
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 80; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ABSORPTION SPECTROSCOPY
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CARCINOMAS
COMBINED THERAPY
DIAGNOSTIC TECHNIQUES
DIFFUSION
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTS
FUNCTIONS
GLANDS
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IN VIVO
INFRARED RADIATION
INFRARED SPECTRA
MAMMALS
MAMMARY GLANDS
MATERIALS
MEDICINE
NEAR INFRARED RADIATION
NECROSIS
NEOPLASMS
NMR IMAGING
NONMETALS
NUCLEAR MEDICINE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN
PATHOLOGICAL CHANGES
PIGMENTS
PORPHYRINS
PROTEINS
RADIATIONS
RADIOLOGY
RADIOTHERAPY
RATS
RESPONSE FUNCTIONS
RODENTS
SPECTRA
SPECTROSCOPY
THERAPY
VERTEBRATES