New SPECT tracers

There is ongoing research into the development of new SPECT tracers. Much of this research is still at the laboratory level using animal models and has not yet reached clinical practice. The aim of this research is to develop a tracer which allows improved myocardial perfusion imaging.

Desirable tracer characteristics:

  • must be taken up by the myocardium rapidly (preferably at first passage of the blood through the myocardium)
  • needs to be retained for long enough to be imaged
  • uptake by other tissues, especially the liver, must be minimal to allow maximum definition of the myocardium
  • the uptake must be in a linear relationship to the myocardial blood flow so that perfusion can be calculated from the tracer uptake

Some new groups of complexes have emerged as potential imaging tracers from this research. These are cationic 99mTc-nitrido complexes and 99mTc(I)-tricarbonyl complexes. These complexes have a crown ether functional group which helps to improve their clearance from the liver and therefore theoretically improves the definition of the inferior wall of the left ventricle from the liver. Of these there is some experimental data for the following three tracers:

1. TC-N-MPO

  • been demonstrated in a rat model to accumulate in the myocardium to the same extent as Tc-MIBI with a higher heart to liver ratio.
  • lower accumulation in the liver with this novel agent is probably as a result of better liver clearance via the MDR transport function of hepatocytes
  • difference in heart liver ratios was not consistent  in other animal models

2. Tc-15C5-PNP

  • tested in rat models
  • demonstrated a similar quality perfusion scan to that of  Tc-MIBI but objectively lower liver activity, although the degree of this has been variable across different laboratories

3. Tc-DBODC5

  • is the most widely tested; even having some human data from a clinical trial
  • rat and canine studies demonstrated an improved heart-to-liver ratio compared to Tc-TETROFUSMIN and Tc-MIBI
  • a phase I clinical study involving ten healthy male volunteers showed good myocardial extraction of the compound. The tracer had reasonable liver elimination giving promising heart-to-liver ratios at rest and stress. However these values showed some similarity to the values from the initial trial of Tc-MIBI, so do not seem to reflect a dramatically different compound

Some research has focused on imaging neuroreceptors in the heart, especially in patients with ischaemic heart disease and heart failure who are at increased risks of arrhythmias. These disease processes are associated with both pre and postsynaptic changes in the cardiac neural system.

  • tracers such as 123I-metaiodobenzylguanidine (123I-MIBG) and 11C-metahydroxyephedrine (11C-HED) can be used in combination with SPECT and PET to chart these changes
  • 123I-MIBG has similar molecular properties to Noradrenaline, therefore in patients with heart failure there is usually a reduced heart to mediastinum uptake ratio
  • some evidence suggests that abnormal cardiac sympathetic function correlates to an increased risk of pump failure and sudden cardiac death in patients with heart failure
  • there are ongoing clinical trials, using 123I-MIBG SPECT and 11C-HED PET imaging, currently evaluating the value of cardiac autonomic assessment in patients with heart failure

SPECT tracers to assess myocardial ischaemia are also in development

  • labelled fatty acid tracers utilise the increased metabolism of fatty acids in an area of ischaemic myocardium
  • 123 I-BMIPP (123I-labeled 15-(p-iodophenyl)3-R,S-methylpentadecanoic acid) can also provide information about myocardial viability in patients with previous myocardial infarctions
  • 123I-IPPA allows identification of ischaemic and probably hibernating myocardium, although this has not been extensively validated
  • 123I-IPPA is rapidly metabolised and requires newer SPECT systems which can acquire dynamic images with sufficient temporal resolution

Other developments

  • new SPECT cameras utilising a gamma ray detector made of cadmium zinc telluride (CZT) may allow the  previously poorly utilised tracer 99mTc-teboroxime to be used in routine clinical practice
  • 99mTc-teboroxime  has a high first pass extraction fraction but poor myocardial retention
  • a CZT containing SPECT camera is a multi-headed gamma camera which allows acquisition of ultra-fast images, which would therefore compensate for the poor cardiac retention of 99mTc-teboroxime.
  • there is also some initial animal data assessing radiolabelled rotenone. 70-Z-[125I]-iodorotenone (ZIROT) has been assessed in rabbit hearts and showed an improved flow versus extraction relationship over the conventional Tc-MIBI tracer
  • no clinical evaluation of ZIROT has yet been undertaken

Overall the development of novel SPECT agents remains ongoing. There is much need for clinical evaluation of these agents as results in animal models seem to be dependent upon the exact model used and therefore only provide limited guidance when translating the results to humans. The development areas for the future remain to optimise the differential uptakes by the heart and liver and identify a tracer than is reliably taken up at faster myocardial blood flow rates.

References

1.    Riou and Broisat. Novel SPECT perfusion imaging agents with improved myocardial or liver kinetics. Journal of Nuclear Cardiology. 2010. 17(5);771-4
2.    Cittanti, Uccelli, Pasquali et al. Whole body biodistribution and radiation dosimetry of the new cardiac tracer 99mTc-N-DBODC. Journal of Nuclear Medicine. 2008. 49;1299-1304

Page last edited: 25 November 2010