In vitro and in vivo properties of (/sup 125/I) (R,S) 4IQNB: A lower affinity diastereomeric muscarinic receptor radiotracer
The (R,R) diastereomer of 3-Quinuclidinyl 4-Iodobenzilate (4IQNB) is a high affinity muscarinic acetylcholine receptor radiotracer which has provided images of receptor distribution in the CNS of man. The radiotracer is of such high affinity that dissociation in vivo is not evident in man after 6-half-lives I-123. Since the dissociation kinetics of radiotracer may be helpful for receptor quantitation, the authors have prepared (/sup 125/I) (R,S) 4IQNB: a diastereomer of 4IQNB which as a lower affinity for the m-AChR than the (R,R) isomer. The equilibrium association constant for the (R,S) diastereomer is 1.10 x 10/sup 9/ M/sup -1/, which is 4-fold lower in affinity than (/sup 3/H) (R) QNB and 2-fold lower than that of the (R,R) 4IQNB. Of more interest, the dissociation rate constant of (R,S) 4IQNB is 0.099 (+0.01)/min., 15-fold more rapid than that of the (R,R) isomer. The systemic distribution of (R,S) 4IQNB is similar to that of (R,R) 4IQNB except localization in the myocardium is 2-fold lower, reflecting the lower affinity. Nonreceptor interactions are the same since the compounds differ only as optical isomers around the carbinol chiral center. In the CNS peak activities are obtained in the corpus striatum (and other M/sub 1/-receptor rich structures) which are the same as obtained with (R,R) 4IQNB. However, no washout of (R,R) 4IQNB is observed after 4 hrs and only 60% in 24 hrs. By contrast, 65% of (R,S) 4IQNB washes out in 4 hrs and no significant activity is detected after 24 hrs. The increased washout kinetics should provide a better radiotracer for determining muscarinic receptor concentrations in the CNS of man.
- Research Organization:
- The George Washington Univ. Medical Center, Washington, DC
- OSTI ID:
- 6651845
- Report Number(s):
- CONF-850611-; TRN: 87-015115
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ACETYLCHOLINE
BIOCHEMICAL REACTION KINETICS
RADIORECEPTOR ASSAY
PARASYMPATHOMIMETICS
LABELLING
RECEPTORS
BIOLOGICAL HALF-LIFE
CHEMICAL PREPARATION
DISSOCIATION
IN VITRO
IN VIVO
INTERACTIONS
IODINE 125
ISOMERS
MAN
OPTICS
REMOVAL
TRACER TECHNIQUES
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
SYNTHESIS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics