Delving into the Latest Updates on Dodecafluoropentane with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

dodecafluoropentane, EchoGen, Perflenapent/Perflisopent

+ [4]

Target

Potassium channel

Mechanism

Potassium channel modulators

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Cardiovascular Diseases

Originator Organization

Sonus Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Sonus Pharmaceuticals, Inc.

Drug Highest PhaseWithdrawn

First Approval Date

EU (17 Jul 1998),

Cardiovascular Diseases

Regulation-

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Structure

Molecular FormulaC5F12

InChIKeyNJCBUSHGCBERSK-UHFFFAOYSA-N

CAS Registry678-26-2

Experiments were conducted on subcutaneous C6 glioma implanted in 37 rats. Twenty-five rats were divided into five groups treated by ultrasound (US) + dodecafluoropentane (DDFP), US + microbubble (MB), US, DDFP, or saline, respectively. ADV was performed using DDFP droplets (2-5 μm) triggered by non-focused pulsed ultrasound. Macroscopic and histological changes of the tumor were compared with investigation of the tumor ablation effect of ADV. Tumor temperature was measured before and immediately after treatment to explore temperature changes. Furthermore, another 12 rats with bilateral tumors were divided into two groups. Six animals received ADV treatment on unilateral tumor, while another six received saline injection on unilateral tumor. The tumor blood perfusion, tumor volume and related immune response were measured.

RESULTS:

The tumors treated by ADV were partially damaged without significant temperature rise. For the animals with bilateral tumors, the tumor blood perfusion around the damaged area on the side receiving ADV still existed. Additionally, the bilateral tumors of animals treated with ADV were smaller than those of animals treated with saline, along with stronger immune response and more tumor cell apoptosis in tumors on both sides.

CONCLUSION:

The study demonstrated that ADV treatment could damage subcutaneous glioma in rats by mechanical effect and enhance systemic immune response to furtherly inhibit the tumor growth.

01 Aug 2023·Cancer research communications

Dodecafluoropentane Emulsion as a Radiosensitizer in Glioblastoma Multiforme.

Article

Author: Lickliter, Jason D ; Ruben, Jeremy ; Jennens, Ross ; Gzell, Cecelia ; Kichenadasse, Ganessan ; Zhou, Heling ; Stea, Baldassarre ; Mason, Ralph P ; Unger, Evan ; Becker, Jennifer

Purpose:

Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM.

Experimental Design:

In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level-dependent) contrast MRI was obtained to validate modulation of tumor hypoxia.

Results:

Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan-Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T₁ was observed after DDFPe treatment.

Conclusions:

This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe.Trial Registration: NCT02189109.

Significance:

This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy.

16 Jun 2023·Intensive care medicine experimental

The impact of intravenous dodecafluoropentane on a murine model of acute lung injury.

Article

Author: Kempf, Carrie ; Mosier, Jarrod M ; Unger, Evan ; Garcia, Joe G N ; Sammani, Saad

INTRODUCTION:

Intravenous oxygen therapeutics present an appealing option for improving arterial oxygenation in patients with acute hypoxemic respiratory failure, while limiting iatrogenic injury from conventional respiratory management.

METHODS:

We used an established two-hit murine model of acute lung injury (ARDS/VILI) to evaluate the effect of intravenous dodecafluoropentane (DDFPe) on oxygen saturation and bronchoalveolar lavage cell counts and protein levels. Twenty hours after challenge with intratracheal lipopolysaccharide, mice were intubated and ventilated with high tidal volumes (4 h) to produce acute lung injury. DDFPe (0.6 mL/kg) or saline was administered by IV bolus injection at the initiation of mechanical ventilation and again at 2 h. Oxygen saturation was measured every 15 min. Bronchoalveolar lavage was performed at the conclusion of the experiment.

RESULTS:

The two-hit ARDS/VILI model produced substantial inflammatory acute lung injury reflected by markedly increased bronchoalveolar lavage (BAL) cell counts compared to BAL cell counts in spontaneous breathing controls (5.29 ± 1.50 × 10^-6 vs 0.74 ± 0.014 × 10^-6 cells/mL) Similarly, BAL protein levels were markedly elevated in ARDS/VILI-challenged mice compared with spontaneous breathing controls (1109.27 ± 223.80 vs 129.6 ± 9.75 ng/mL). We fit a linear mixed effects model that showed a significant difference in oxygen saturation over time between DDFPe-treated mice and saline-treated mice, with separation starting after the 2-h injection. DDFPe-treated ARDS/VILI-challenged mice also exhibited significant reductions in BAL cell counts but not in BAL protein.

CONCLUSION:

DDFPe improves oxygen saturation in a murine model of ARDS/VILI injury with the potential for serving as an intravenous oxygen therapeutic.

100 Deals associated with Dodecafluoropentane

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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Cardiovascular Diseases	EU	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	IS	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	LI	Sonus Pharmaceuticals, Inc.	17 Jul 1998
Cardiovascular Diseases	NO	Sonus Pharmaceuticals, Inc.	17 Jul 1998

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02963376 (Pubmed \| J Vasc Interv Radiol) Manual	Phase 1/2	Acute Ischemic Stroke	24	Dodecafluoropentane	tfamunudcq(hvgniodscl) = Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = 0.03). oxyhtbkykk (bhhkiwykso ) View more	Positive	01 Aug 2019
NCT02963376 (Pubmed \| J Vasc Interv Radiol) Manual	Phase 1/2	Acute Ischemic Stroke	24	Placebo		Positive	01 Aug 2019
ISC2015	Not Applicable	-	6	Dodecafluoropentane emulsion	gxydykszvx(mnprslsmng) = rqzjlsmofp ocyjfwtgez (tmoxddvltz ) View more	-	01 Feb 2015
ISC2013	Not Applicable	-	8	Dodecafluoropentane Emulsion (Single bolus (0.6 mL/kg))	onmomxgvld(csajpceymd) = bdbsxryetl jlvtpqeehz (oiklaqwzxc ) View more	-	01 Feb 2013