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99mTc carbonyl t-butyl isonitrile: A potential new agent for myocardial perfusion imaging

Kothari, Kanchan K.a; Satpati, Drishtya; Joshi, Sangeetab; Venkatesh, Meeraa b; Ramamoorthy, Natesana b; Pillai, Maroor R.A.a

Nuclear Medicine Communications: February 2005 - Volume 26 - Issue 2 - p 155-161

Objective The recent development of mixed ligand complexes using a 99mTc tricarbonyl synthon has prompted us to revisit the first generation product, 99mTc-t-butyl isonitrile (TBI), for possible myocardial imaging after modification of the 99mTc core to a mixed ligand core of carbonyl and t-butyl isonitrile. The easy availability of TBI from commercial sources and the recent promising development of a ‘kit’ procedure to prepare the 99mTc tricarbonyl aqua synthon/precursor [99mTc(H2O)3(CO)3]+ were other factors that triggered this work.

Methods The carbonyl precursor (37–370 MBq/0.5 ml) was synthesized and reacted with TBI (3 mg·ml−1) at room temperature and at pH 8 for 1 h. [99mTc(CO)3(TBI)3]+ was characterized by C18 reverse phase HPLC in gradient mode with water and acetonitrile as solvent. Biodistribution studies were carried out in normal mice and planar images were acquired in rabbit at 5 min, 30 min, 1 h, 2 h and 4 h post-injection to assess heart uptake and soft tissue retention. [99mTc(CO)3(TBI)3]+ was formed as a single species in >95% yield and was found to be stable. Biodistribution studies in mice revealed 2.3 (±0.2)% uptake in heart at 5 min p.i. with heart/liver, heart/lung and heart/blood ratios of 1.5, 2.0 and 30, respectively. Imaging studies in rabbits showed high uptake in myocardium, with negligible activity in blood and lungs, at 5 min p.i. that washed out of the heart after 4 h.

Conclusion [99mTc(CO)3(TBI)3]+ could be prepared in >95% yields. The complex showed high myocardial uptake with desirable rate of washout from heart in rabbits. [99mTc(CO)3(TBI)3]+ has potential to extend to larger animal studies and later for clinical evaluation as a myocardial imaging agent.

aRadiopharmaceuticals Division, Isotope Group, Bhabha Atomic Research Centre, Mumbai, India

bBoard of Radiation and Isotope Technology, BARC, Mumbai, India

Correspondence to Dr Kanchan Kothari, Radiopharmaceuticals Division, Isotope Group, Bhabha Atomic Research Centre, Mumbai 400085, India

Tel: +91 255 90616; fax: +91 22 2550 5345 & 255 19613;


Received 4 May 2004 Revised 10 September 2004 Accepted 29 September 2004

© 2005 Lippincott Williams & Wilkins, Inc.