Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with (99m)Tc- and (123)I-labelled probes

Eur J Nucl Med Mol Imaging. 2009 Sep;36(9):1495-509. doi: 10.1007/s00259-009-1142-9. Epub 2009 May 7.

Abstract

Purpose: The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.

Methods: A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor.

Results: In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.

Conclusion: Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

MeSH terms

  • Animals
  • Benzamides / pharmacokinetics
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / metabolism
  • Heart / diagnostic imaging*
  • Humans
  • Iodine Radioisotopes*
  • Iodobenzenes / pharmacokinetics
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism
  • Oximes / pharmacokinetics
  • Pyrrolidines / pharmacokinetics
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP3 Subtype
  • Swine
  • Technetium Tc 99m Sestamibi / pharmacokinetics
  • Technetium*
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Benzamides
  • Iodine Radioisotopes
  • Iodobenzenes
  • Oximes
  • PTGER3 protein, human
  • Ptger3 protein, mouse
  • Pyrrolidines
  • Radiopharmaceuticals
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • hexamethylpropyleneamine oxime
  • Technetium
  • omega-(4-iodophenyl)pentadecanoic acid
  • 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
  • Technetium Tc 99m Sestamibi