AI Article Synopsis

  • Hypoxic zones in tumors make them resistant to radiation therapy, but drugs that improve oxygen levels, like SQAP, can enhance treatment effectiveness.
  • The study used various imaging techniques to show how SQAP affects oxygen levels and blood flow in tumors before radiation.
  • Results indicated that SQAP improves tumor oxygenation and blood perfusion, leading to better responses to radiation therapy and potentially delaying tumor growth.

Article Abstract

: Hypoxic zones in solid tumors contribute to radioresistance, and pharmacologic agents that increase tumor oxygenation prior to radiation, including antiangiogenic drugs, can enhance treatment response to radiotherapy. Although such strategies have been applied, imaging assessments of tumor oxygenation to identify an optimum time window for radiotherapy have not been fully explored. In this study, we investigated the effects of α-sulfoquinovosylacyl-1,3-propanediol (SQAP or CG-0321; a synthetic derivative of an antiangiogenic agent) on the tumor microenvironment in terms of oxygen partial pressure (pO), oxyhemoglobin saturation (sO), blood perfusion, and microvessel density using electron paramagnetic resonance imaging, photoacoustic imaging, dynamic contrast-enhanced MRI with Gd-DTPA injection, and T2*-weighted imaging with ultrasmall superparamagnetic iron oxide (USPIO) contrast. SCCVII and A549 tumors were grown by injecting tumor cells into the hind legs of mice. Five days of daily radiation (2 Gy) combined with intravenous injection of SQAP (2 mg/kg) 30 minutes prior to irradiation significantly delayed growth of tumor xenografts. Three days of daily treatment improved tumor oxygenation and decreased tumor microvascular density on T2*-weighted images with USPIO, suggesting vascular normalization. Acute effects of SQAP on tumor oxygenation were examined by pO, sO, and Gd-DTPA contrast-enhanced imaging. SQAP treatment improved perfusion and tumor pO (ΔpO: 3.1 ± 1.0 mmHg) and was accompanied by decreased sO (20%-30% decrease) in SCCVII implants 20-30 minutes after SQAP administration. These results provide evidence that SQAP transiently enhanced tumor oxygenation by facilitating oxygen dissociation from oxyhemoglobin and improving tumor perfusion. Therefore, SQAP-mediated sensitization to radiation can be attributed to increased tumor oxygenation. SIGNIFICANCE: A multimodal molecular imaging study evaluates pharmacological alteration of the tumor microenvironment to improve radiation response.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127870PMC
http://dx.doi.org/10.1158/0008-5472.CAN-18-1654DOI Listing

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