Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from various clinical conditions. It may be idiopathic (of unknown cause) or associated with numerous diseases including cardiovascular and lung disorders. Affected individuals suffer from progressive shortness of breath and, in its most sever forms; pulmonary hypertension carries a worse prognosis than many types of cancer. There is no test currently that can easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there is no cure for pulmonary hypertension and substantial research efforts are dedicated to the development of new drugs that will stop progression or better yet, reverse the disease process. The investigators do not know if any of the drugs currently commercialized for pulmonary hypertension directly improve the status of the pulmonary vessels since no test currently provides this information. Direct earlier detection of lung vessel abnormalities associated with pulmonary hypertension using a sensitive and non-invasive test would allow not only earlier testing of these and of new drugs, but would provide a much better surrogate of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension and its potential to detect abnormal pulmonary circulation associated within pulmonary hypertension.

开始日期2014-09-01

申办/合作机构

Montréal Heart Institute

NCT01539889 / Completed临床1期IIT

Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation

Pulmonary hypertension (PH) can be the result of various clinical conditions. It may be idiopathic or associated with various cardiovascular and lung disorders. Currently there is no test that can non-invasively detect abnormalities of the pulmonary circulation. There is a growing need for a non-invasive method to detect PH. There currently exists only ne agent approved in Canada for clinical imaging of the pulmonary circulation, 99mTc-labeled macroaggregates. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. This agent is larger than small pulmonary vessels, limiting its sensitivity to detect small vascular defects, as well as potential infectious risks since albumin macroaggregates are derived from human albumin. There is need then for new lung tracers that could provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Hence the development of this novel AM derivative, PulmoBind, for molecular imaging of the pulmonary circulation. PulmoBind is labeled with 99mTc, the most commonly used imaging isotope in nuclear medicine.

开始日期2011-12-01

申办/合作机构

Montréal Heart Institute

100 项与 DFH-12 相关的临床结果

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100 项与 DFH-12 相关的转化医学

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100 项与 DFH-12 相关的专利（医药）

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项与 DFH-12 相关的文献（医药）

2021-12-01·Respiratory Research2区 · 医学

SPECT imaging of pulmonary vascular disease in bleomycin-induced lung fibrosis using a vascular endothelium tracer

2区 · 医学

ArticleOA

作者: Nsaibia, Mohamed J ; Bergeron, Alexandre ; Shi, YanFen ; Tardif, Jean-Claude ; Nguyen, Quang T ; Calderone, Angelino ; Brochiero, Emmanuelle ; Harel, François ; Sirois, Martin ; Villeneuve, Louis ; Morgan, Arielle ; Dupuis, Jocelyn ; Finnerty, Vincent

AbstractBackgroundPulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is associated to worse outcome. There is a great need for a non-invasive diagnostic modality to detect and evaluate the severity of pulmonary vascular disease (PVD). 99mTc-PulmoBind is a novel imaging agent that binds to the adrenomedullin (AM) receptor on the pulmonary microvascular endothelium. SPECT imaging employing the endothelial cell tracer 99mTc-PulmoBind was used to assess PVD associated with lung fibrosis.MethodsRats with selective right lung bleomycin-induced fibrosis were compared to control rats. SPECT imaging was performed after three weeks with 99mTc-PulmoBind and 99mTc-macroaggregates of albumin (MAA). PH and right ventricular (RV) function were assessed by echocardiography. Lung perfusion was evaluated by fluorescent microangiography. Lung AM receptor expression was measured by qPCR and by immunohistology. Relevance to human IPF was explored by measuring AM receptor expression in lung biopsies from IPF patients and healthy controls.ResultsThe bleomycin group developed preferential right lung fibrosis with remodeling and reduced perfusion as assessed with fluorescent microangiography. These rats developed PH with RV hypertrophy and dysfunction. 99mTc-PulmoBind uptake was selectively reduced by 50% in the right lung and associated with reduced AM receptor expression, PH and RV hypertrophy. AM receptor was co-expressed with the endothelial cell protein CD31 in alveolar capillaries, and markedly reduced after bleomycin. Quantitative dynamic analysis of 99mTc-PulmoBind uptake in comparison to 99mTc-MAA revealed that the latter distributed only according to flow, with about 60% increased left lung uptake while left lung uptake of 99mTc-PulmoBind was not affected. Lung from human IPF patients showed important reduction in AM receptor expression closely associated with CD31.ConclusionsSPECT imaging with 99mTc-PulmoBind detects PVD and its severity in bleomycin-induced lung fibrosis. Reduced AM receptor expression in human IPF supports further clinical development of this imaging approach.

2017-07-01·European Journal of Nuclear Medicine and Molecular Imaging1区 · 医学

Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

1区 · 医学

Article

作者: Nguyen, Quang T ; Langleben, David ; Abikhzer, Gad ; Levac, Xavier ; Letourneau, Myriam ; Guertin, Marie-Claude ; Harel, François ; Dupuis, Jocelyn ; Provencher, Steve ; Finnerty, Vincent ; Guimond, Jean ; Fournier, Alain ; Mansour, Asmaa

PURPOSEThe adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study.METHODSThirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi ^99mTc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month.RESULTSPulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∼50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution.CONCLUSIONSIn this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using ^99mTc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and direct comparisons to lung perfusion agents such as labeled macro-aggregates of albumin are needed.CLINICAL TRIALClinicalTrials.gov, NCT02216279.

2016-12-01·EJNMMI Research

Evaluation of pulmonary perfusion by SPECT imaging using an endothelial cell tracer in supine humans and dogs

Article

作者: Nguyen, Quang T ; Finnerty, Vincent ; Harel, François ; Levac, Xavier ; Letourneau, Myriam ; Fournier, Alain ; Marcil, Sophie ; Dupuis, Jocelyn

BACKGROUNDPulmonary perfusion is not spatially homogeneously distributed, and its variations could be of diagnostic value in lung vascular disease. PulmoBind is a ligand of the adrenomedullin receptor densely expressed in endothelial cells of lung capillaries. The aim of this study was to evaluate spatial distribution of human lung perfusion by using this novel molecular tracer of the pulmonary vascular endothelium.METHODSNormal humans (n = 19) enrolled into the PulmoBind phase I trial were studied (Clinicaltrials.gov. NCT01539889 ). They were injected with (99m)Tc-PulmoBind for SPECT imaging. Results were compared with (99m)Tc-PulmoBind in quadruped mammals (dogs, n = 5). Imaging was performed in the supine position and distribution of activity was determined as a function of cumulative voxels along the different anatomical planes.RESULTSPulmoBind uptake in humans was 58 ± 1 % (mean ± SEM) of the injected dose. Dorsal activity was 18.1 ± 2.1 % greater than ventral, and caudal activity was 25.7 ± 1.6 % greater than cranial. Lateral activity was only mildly higher than medial by 7.0 ± 1.0 %. In supine dogs, similar but higher PulmoBind gradients were present: dorsal 28.6 ± 2.5 %, caudal 34.1 ± 5.0 % and lateral 18.1 ± 2.0 %.CONCLUSIONSThe perfused pulmonary circulation of supine humans, assessed by an adrenomedullin receptor ligand, is not homogeneously distributed with more prominent distribution in dorsal and caudal regions. It is qualitatively similar to a supine quadruped mammal confirming the presence of a microcirculatory gravitational perfusion gradient detectable with this tracer. Future studies are needed to determine if this novel endothelial cell tracer could be used to detect physiologic and pathologic variations of lung perfusion such as in pulmonary hypertension.CLINICAL TRIALClinicalTrial.gov, NCT01539889.

100 项与 DFH-12 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肺性高血压	临床2期	加拿大	Montréal Heart Institute	2014-09-01
肺动脉高压	临床2期	-	Montréal Heart Institute	-
肺动脉高压	临床2期	-	Pulmo BioTech, Inc.	-
肺栓塞	临床2期	-	Pulmo BioTech, Inc.	-
肺栓塞	临床2期	加拿大	-	-
肺栓塞	临床2期	-	Montréal Heart Institute	-