Radiolabeled ligands for imaging the muscarinic-cholinergic receptors of the heart and brain.
Interest in the potential use of cerebral SPECT and PET imaging for determination of the density and activity of muscarinic-cholinergic receptors (mAChR) has been stimulated by the changes in these receptors which occur in many neurological diseases. In addition, the important involvement of mAChR in modulating negative inotropic cardiac activity suggests that such receptor ligands may have important applications in evaluation of changes which may occur in cardiac disease. In this paper, the properties of several key muscarinic receptor ligands being developed or which have been used for clinical SPECT and PET are discussed. In addition, the ORNL development of the new iodinated IQNP ligand based on IQNB and the results of in vivo biodistribution studies in rats, in vitro competitive binding studies and ex vivo autoradiographic experiments are described. The use of radioiodinated IQNP may offer several advantages in comparison to IQNB because of its easy and high yield preparation and high brain uptake and the potential usefulness of the "partial" subtype selective IQNP isomers. We also describe the development of new IQNP-type analogues which offer the opportunity for radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and bromine-76) for potential use with PET.
Knapp
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Health Sciences Research Division Oak Ridge National Laboratory (ORNL), Tennessee 37831-6229, USA. JKP@ornl.gov
McPherson
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Luo
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Zeeburg
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B
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001967:Bromine Radioisotopes; D002250:Carbon Radioisotopes / Q000627:therapeutic use; D005462:Fluorine Radioisotopes / Q000627:therapeutic use; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D008024:Ligands; D009206:Myocardium / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D001967:Bromine Radioisotopes; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D008024:Ligands; D011976:Receptors, Muscarinic