MRI-Tracked Tumor Vascular Changes in the Hours after Single-Fraction Irradiation

Brown, Stephen L.; Nagaraja, Tavarekere N.; Aryal, Madhava; Panda, Swayamprava; Cabral, Glauber; Keenan, Kelly A.; Elmghirbi, Rasha; Mikkelsen, Tom; Hearshen, David; Knight, Robert A.; Wen, Ning; Kim, Jae Ho; Ewing, James R.

doi:10.1667/rr13458.1

Cited by 31 publications

(28 citation statements)

References 34 publications

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“…Timing-dependent outcomes appear to be related to acute changes in the tumor vascular physiology in the hours after a monotreatment or combined treatments (4, 5, 7, 8, 19). Furthermore, by tracking short-term changes in tumor vascular physiology, a beneficial timing of the combined therapies can be identified, leading to better treatment outcome and OS.…”

Section: Discussionmentioning

confidence: 99%

“…(7), and of irradiation alone reported by Brown et al . (8). Nagaraja and colleagues tracked the short-term changes in the tumor vascular parameters (K trans and v e ) at 2, 4, 8, 12 and 24 h after Cilengitide administration in an orthotopic U-251 glioma model.…”

Section: Discussionmentioning

confidence: 99%

“…(8). Briefly, radiation was delivered using a clinical linear accelerator operating at 6 MV photons (Varian Trilogy, Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Since these potential “synergies” are short-term with respect to tumor response, and many of the agents affect tumor vasculature, it might be expected that the short-term changes in tumor physiology which occur in response to combined treatments could be used as biomarkers of response. Indeed, studies in preclinical models (7, 8) showed that tumor physiology changes profoundly in the hours after either anti-angiogenic treatment or irradiation. In current clinical practice, short-term anatomical changes don’t occur and short-term physiological responses are not usually assessed.…”

Section: Introductionmentioning

confidence: 99%

“…The importance of optimizing the timing and sequence of combined therapies such as radiotherapy with anti-angiogenic drugs has become increasingly recognized (15–18), as has the importance of acute tumor responses to therapies (4, 5, 7, 8, 19). In this study, we investigated the timing between Cilengitide and radiation exposure to determine the vascular signature corresponding to increased tumor response to combined treatments.…”

Section: Introductionmentioning

confidence: 99%

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Acute Temporal Changes of MRI-Tracked Tumor Vascular Parameters after Combined Anti-angiogenic and Radiation Treatments in a Rat Glioma Model: Identifying Signatures of Synergism

et al. 2017

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In this study we used magnetic resonance imaging (MRI) biomarkers to monitor the acute temporal changes in tumor vascular physiology with the aim of identifying the vascular signatures that predict response to combined anti-angiogenic and radiation treatments. Forty-three athymic rats implanted with orthotopic U-251 glioma cells were studied for approximately 21 days after implantation. Two MRI studies were performed on each animal, pre- and post-treatment, to measure tumor vascular parameters. Two animal groups received treatment comprised of Cilengitide, an anti-angiogenic agent and radiation. The first group received a subcurative regimen of Cilengitide 1 h before irradiation, while the second group received a curative regimen of Cilengitide 8 h before irradiation. Cilengitide was given as a single dose (4 mg/kg; intraperitoneal) after the pretreatment MRI study and before receiving a 20 Gy radiation dose. After irradiation, the post-treatment MRI study was performed at selected time points: 2, 4, 8 and 12 h (n = ≥5 per time point). Significant changes in vascular parameters were observed at early time points after combined treatments in both treatment groups (1 and 8 h). The temporal changes in vascular parameters in the first group (treated 1 h before exposure) resembled a previously reported pattern associated with radiation exposure alone. Conversely, in the second group (treated 8 h before exposure), all vascular parameters showed an initial response at 2–4 h postirradiation, followed by an apparent lack of response at later time points. The signature time point to define the “synergy” of Cilengitide and radiation was 4 h postirradiation. For example, 4 h after combined treatments using a 1 h separation (which followed the subcurative regimen), tumor blood flow was significantly decreased, nearly 50% below baseline (P = 0.007), whereas 4 h after combined treatments using an 8 h separation (which followed the curative regimen), tumor blood flow was only 10% less than baseline. Comparison between the first and second groups further revealed that most other vascular parameters were maximally different 4 h after combined treatments. In conclusion, the data are consistent with the assertion that the delivery of radiation at the vascular normalization time window of Cilengitide improves radiation treatment outcome. The different vascular responses after the different delivery times of combined treatments in light of the known tumor responses under similar conditions would indicate that timing has a crucial influence on treatment outcome and long-term survival. Tracking acute changes in tumor physiology after monotherapy or combined treatments appears to aid in identifying the beneficial timing for administration, and perhaps has predictive value. Therefore, judicial timing of treatments may result in optimal treatment response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…(8). Briefly, radiation was delivered using a clinical linear accelerator operating at 6 MV photons (Varian Trilogy, Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acute Temporal Changes of MRI-Tracked Tumor Vascular Parameters after Combined Anti-angiogenic and Radiation Treatments in a Rat Glioma Model: Identifying Signatures of Synergism

et al. 2017

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Effects of radiation on tumor vasculature

Yamazaki

Young

2021

Molecular Carcinogenesis

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Radiation has been utilized as a direct cytotoxic tumorcidal modality, however, the effect of radiation on tumor vasculature influences response to anticancer therapies.Although numerous reports have demonstrated vascular changes in irradiated tumors, the findings and implications are extensive and at times contradictory depending on the radiation dose, timing, and models used. In this review, we focus on the radiation-mediated effects on tumor vasculature with respect to doses used, timing postradiation, vasculogenesis, adhesion molecule expression, permeability, and pericyte coverage, including the latest findings.

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Toward a noninvasive estimate of interstitial fluid pressure by dynamic contrast‐enhanced MRI in a rat model of cerebral tumor

Elmghirbi

Nagaraja

Brown

et al. 2018

Magnetic Resonance in Med

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MRI-Tracked Tumor Vascular Changes in the Hours after Single-Fraction Irradiation

Cited by 31 publications

References 34 publications

Acute Temporal Changes of MRI-Tracked Tumor Vascular Parameters after Combined Anti-angiogenic and Radiation Treatments in a Rat Glioma Model: Identifying Signatures of Synergism

Acute Temporal Changes of MRI-Tracked Tumor Vascular Parameters after Combined Anti-angiogenic and Radiation Treatments in a Rat Glioma Model: Identifying Signatures of Synergism

Effects of radiation on tumor vasculature

Toward a noninvasive estimate of interstitial fluid pressure by dynamic contrast‐enhanced MRI in a rat model of cerebral tumor

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