Clinical feasibility study to detect angiogenesis following bone marrow stem cell transplantation in chronic ischaemic heart failure.
BACKGROUND
Bone marrow stem cell (BMSC) therapy for cardiovascular disease has shown considerable preclinical and clinical promise, but there remains a need for mechanistic studies to help bridge the transition from bench to bedside. We have designed a substudy to our REGENERATE-IHD trial (ClinicalTrial.gov Identifier: NCT00747708) to assess the feasibility of a novel imaging technique to detect angiogenesis following BMSC therapy.


RESULTS
Nine patients who had been randomized to receive intracoronary injection of G-CSF-mobilized BMSCs or control (serum) were included in this substudy. Patients underwent SPECT imaging using a novel radiolabelled peptide (Tc-NC100692), which has a high affinity for the αvβ3 integrin, an angiogenesis-related integrin. This was repeated 4 days after intracoronary injection of BMSCs/control to assess for neoangiogenesis. The imaging study was well tolerated with no adverse effects. Myocardial tracer uptake was detectable at baseline in all nine patients, with no myocardial uptake seen in two control patients used for comparison. Baseline uptake appeared to correlate with baseline ejection fraction but changes with therapy did not reach statistical significance.


CONCLUSIONS
SPECT imaging with a Tc-NC100692 is feasible in patients with heart failure, with baseline activity suggesting persistent angiogenesis in patients with remote myocardial infarction.
aDepartment of Cardiology, The London Chest Hospital bInstitute of Nuclear Medicine, University College London Hospital cBritish Heart Foundation Laboratories, University College London, London, UK dSection of Cardiovascular Medicine, School of Medicine, Yale University, New Haven, Connecticut, USA eDepartment of Nuclear Medicine, Karolinska University Hospital, Huddinge, Sweden fCentre for Medical Radiation Physics, University of Wollongong, Wollongong, New South Wales, Australia.
Abdul M
AM
Mozid
Maria
M
Holstensson
Tawfiq
T
Choudhury
Simona
S
Ben-Haim
Rayjanah
R
Allie
John
J
Martin
Albert J
AJ
Sinusas
Brian F
BF
Hutton
Anthony
A
Mathur
D001854:Bone Marrow Cells / Q000166:cytology*; D002908:Chronic Disease; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications*; D018919:Neovascularization, Physiologic; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D033581:Stem Cell Transplantation; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; C514230:technetium 99m NC 100692