Effect of trans sodium crocetinate on brain tumor oxgenation

Sheehan, Jason P.; Sherman, Jonathan H; Cifarelli, Christopher P.; Jagannathan, Jay; Dassoulas, Kasandra; Olson, Claire; Rainey, Jessica; Han, Shaojie

doi:10.3171/2009.3.jns081339

Cited by 23 publications

(15 citation statements)

References 19 publications

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“…Briefly, hypoxic sensitizers, such as imidazoles, efaproxiral, and tirapazamine, did not show a significant advantage when used in combination with EBRT in different Phase II trials; 14 other agents, such as trans sodium crocetinate, are undergoing preclinical investigation. 64,65 Disappointing results were also obtained with the S-phase sensitizers, such as bromodeoxyuridine, as well as for the cytotoxic agents including camptothecins, platinum agents, and taxanes. Different is the case for TMZ, an alkylating agent with activity in primary and recurrent gliomas; 9,51,[73][74][75][76][77][78] preclinical data have shown additive or even synergistic activity in combination with radiotherapy.…”

Section: Future Perspectivesmentioning

confidence: 99%

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Romanelli

Conti²,

Pontoriero

et al. 2009

FOC

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Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

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Section: Future Perspectivesmentioning

confidence: 99%

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Romanelli

Conti²,

Pontoriero

et al. 2009

FOC

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“…By comparison, in a different tumor model, the agent trans sodium crocetinate (oxygen diffusion enhancer) increased tumor pO 2 by 40%. 34 The oxygen electrode used in our studies provided pO 2 and blood flow data from a single point within the tumor tissue. In the tumors that were most necrotic, the pO 2 was zero in some of the tumors and the zones of the tumors that were entered by the probes were likely avascular.…”

Section: Discussionmentioning

confidence: 99%

Radiosensitization of Hs-766T Pancreatic Tumor Xenografts in Mice Dosed with Dodecafluoropentane Nano-Emulsion–Preliminary Findings

Johnson¹,

Leos²,

Baker³

et al. 2015

j biomed nanotechnol

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Tumor hypoxia is an important mediator of radiation therapy resistance. We conducted a study to investigate whether an oxygen therapeutic based upon dodecafluoropentane (DDFP) nano-emulsion (NVX-108) could increase tumor pO2 in hypoxic tumors and improve radiation response. Pancreatic (Hs-766T) tumor xenografts were grown in the flanks of 29 SCID mice. Direct tumor pO2 measurements were performed in 9 mice treated with 0.3, 0.45 and 0.6 cc/kg NVX-108 (2% w/vol DDFP) in order to assess the dose dependent increase in tumor pO2. Twenty mice were randomized into 3 groups including control (no treatment), carbogen breathing treated with 12 Gy radiation, and carbogen breathing treated with 12 Gy radiation and NVX-108 (0.6 cc/kg NVX-108 administered as 30 minute IV infusion at time of radiation). Tumor volume was monitored to assess treatment efficacy. Results showed that tumor pO2 increased in NVX-108 treated mice up to 400% with the greatest effect seen at the highest dose of 0.6 cc/kg. Tumor growth was significantly reduced in both treatment groups relative to controls (p < 0.0001). The combination of carbogen, radiation, and NVX-108 demonstrated a 2-fold reduction in average tumor volume compared to carbogen plus radiation treatment (p = 0.01). Further study of NVX-108 as a radiation sensitizer is warranted.

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“…Rather, TSC increases hydrogen bonding of neighboring water molecules, resulting in a condition known as “structure-building”, which reduces the resistance to the diffusion of small molecules. Recent studies have demonstrated that TSC can increase oxygen levels in normal brain and in brain tumors ( Okonkwo et al 2003; Sheehan et al 2009). Moreover, TSC was shown to reduce the depth of hypoxia in the ischemic penumbra of a 3VO model by approximately 55% ( Manabe et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Elevating intra-tumor oxygen could reestablish radiosensitivity in glioma cells, thus making the tumors less resistant to RT. Sheehan and associates have provided evidence that TSC can increase intratumor tissue oxygenation and enhance the effects of RT in a rat syngeneic model of GBM ( Sheehan et al 2008; Sheehan et al 2009; Sheehan et al 2010). The Phase I/II clinical trial testing this strategy is currently in progress with an initial enrollment of 60 patients at 18 sites.…”

Section: Discussionmentioning

confidence: 99%

Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke

et al. 2014

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Trans-sodium crocetinate (TSC) is a novel carotenoid compound capable of enhancing the diffusion of small molecules in aqueous solutions. TSC improves the diffusion of oxygen and glucose, and increases oxygenation in ischemic brain tissue. TSC also dampens the intensity of an ischemic challenge during an ongoing ischemic event. The current study examined the impact of TSC in rat models of ischemic and hemorrhagic stroke. Rat three vessel occlusion (3VO), and combined 3VO and one vessel occlusion (3VO/1VO) models of ischemic stroke were evaluated for structural and behavioral outcomes. The effects of TSC were also tested in a rat model of intracerebral hemorrhage (ICH). Delayed treatment with TSC reduced infarct volume in a rodent model of transient focal ischemia involving either 2 or 6 hours of ischemia. Neurological outcomes, based on a multi-scale assessment and automated gait analysis, also were improved by TSC treatment. Additionally, TSC reduced edema and hemorrhagic volume in a rat model of ICH. An optimal therapeutic candidate for early intervention in ischemic stroke should be effective when administered on a delayed basis and should not aggravate outcomes associated with hemorrhagic stroke. The current findings demonstrate that delayed TSC treatment improves outcomes in experimental models of both ischemic and hemorrhagic stroke. Together, these findings suggest that TSC may be a safe and beneficial therapeutic modality for early stroke intervention, irrespective of the type of stroke involved.

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Effect of trans sodium crocetinate on brain tumor oxgenation

Abstract: Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.

Cited by 23 publications

References 19 publications

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Radiosensitization of Hs-766T Pancreatic Tumor Xenografts in Mice Dosed with Dodecafluoropentane Nano-Emulsion–Preliminary Findings

Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke

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