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Title: Nuclear Medicine Program progress report for quarter ending June 30, 1993

Abstract

The ``IQNP`` agent is an antagonist for the cholinergic-muscarinic receptor. Since the IQNP molecule has two asymmetric centers and either cis or trans isomerism of the vinyl iodide, there are eight possible isomeric combinations. In this report, the systematic synthesis, purification and animal testing of several isomers of radioiodinated ``IQNP`` are reported. A dramatic and unexpected relation between the absolute configuration at the two asymmetric centers and the stereochemistry of the vinyl iodide on receptor specificity was observed. The E-(R)(R) isomer shows specific and significant localization (per cent dose/gram at 6 hours) in receptor-rich cerebral structures (i.e. Cortex = 1.38 + 0.31; Striatum = 1.22 + 0.20) and low uptake in tissues rich in the M{sub 2} subtype (Heart = 0.10; Cerebellum = 0.04). In contrast, the E-(R)(S) isomer shows very low receptor-specific uptake (Cortex = 0.04; Striatum = 0.02), demonstrating the importance of absolute configuration at the acetate center. An unexpected and important observation is that the stereochemistry of the vinyl iodine appears to affect receptor subtype specificity, since the Z-(R,S)(R) isomer shows much higher uptake in the heart (0.56 + 0.12) and cerebellum (0.17 + 0.04). Studies are now in progress to confirm these exciting results in vitro.more » Progress has also continued during this period with several collaborative programs. The first large-scale clinical tungsten-188/rhenium-188 generator prototype (500 mCi) was fabricated and supplied to the Center for Molecular Medicine and Immunology (CMMI), in Newark, New Jersey, for Phase I clinical trials of rhenium-188-labeled anti CEA antibodies for patient treatment. Collaborative studies are also continuing in conjunction with the Nuclear Medicine Department at the University of Massachusetts where a generator is in use to compare the biological properties of {open_quotes}direct{close_quotes} and {open_quotes}indirect{close_quotes} labeled antibodies.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Oak Ridge National Lab., TN (United States)
Sponsoring Org.:
USDOE, Washington, DC (United States)
OSTI Identifier:
10176496
Report Number(s):
ORNL/TM-12411
ON: DE93018493; TRN: 93:002893
DOE Contract Number:  
AC05-84OR21400
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: Jul 1993
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; RADIOISOTOPE GENERATORS; DESIGN; RADIOPHARMACEUTICALS; CHEMICAL PREPARATION; PARASYMPATHOMIMETICS; LABELLING; TISSUE DISTRIBUTION; PROGRESS REPORT; NUCLEAR MEDICINE; TUNGSTEN 188; RHENIUM 188; IMMUNOLOGY; ANTIBODIES; ORGANIC IODINE COMPOUNDS; RADIORECEPTOR ASSAY; RECEPTORS; TRACER TECHNIQUES; IODINE 125; STRUCTURE-ACTIVITY RELATIONSHIPS; RATS; BRAIN; HEART; BLOOD; 550601; 400703; UNSEALED RADIONUCLIDES IN DIAGNOSTICS; RADIOISOTOPE PRODUCTION

Citation Formats

Knapp, Jr, F F, Ambrose, K R, Beets, A L, Callahan, A P, Hsieh, B T, McPherson, D W, Mirzadeh, S, and Lambert, C R. Nuclear Medicine Program progress report for quarter ending June 30, 1993. United States: N. p., 1993. Web. doi:10.2172/10176496.
Knapp, Jr, F F, Ambrose, K R, Beets, A L, Callahan, A P, Hsieh, B T, McPherson, D W, Mirzadeh, S, & Lambert, C R. Nuclear Medicine Program progress report for quarter ending June 30, 1993. United States. doi:10.2172/10176496.
Knapp, Jr, F F, Ambrose, K R, Beets, A L, Callahan, A P, Hsieh, B T, McPherson, D W, Mirzadeh, S, and Lambert, C R. Thu . "Nuclear Medicine Program progress report for quarter ending June 30, 1993". United States. doi:10.2172/10176496. https://www.osti.gov/servlets/purl/10176496.
@article{osti_10176496,
title = {Nuclear Medicine Program progress report for quarter ending June 30, 1993},
author = {Knapp, Jr, F F and Ambrose, K R and Beets, A L and Callahan, A P and Hsieh, B T and McPherson, D W and Mirzadeh, S and Lambert, C R},
abstractNote = {The ``IQNP`` agent is an antagonist for the cholinergic-muscarinic receptor. Since the IQNP molecule has two asymmetric centers and either cis or trans isomerism of the vinyl iodide, there are eight possible isomeric combinations. In this report, the systematic synthesis, purification and animal testing of several isomers of radioiodinated ``IQNP`` are reported. A dramatic and unexpected relation between the absolute configuration at the two asymmetric centers and the stereochemistry of the vinyl iodide on receptor specificity was observed. The E-(R)(R) isomer shows specific and significant localization (per cent dose/gram at 6 hours) in receptor-rich cerebral structures (i.e. Cortex = 1.38 + 0.31; Striatum = 1.22 + 0.20) and low uptake in tissues rich in the M{sub 2} subtype (Heart = 0.10; Cerebellum = 0.04). In contrast, the E-(R)(S) isomer shows very low receptor-specific uptake (Cortex = 0.04; Striatum = 0.02), demonstrating the importance of absolute configuration at the acetate center. An unexpected and important observation is that the stereochemistry of the vinyl iodine appears to affect receptor subtype specificity, since the Z-(R,S)(R) isomer shows much higher uptake in the heart (0.56 + 0.12) and cerebellum (0.17 + 0.04). Studies are now in progress to confirm these exciting results in vitro. Progress has also continued during this period with several collaborative programs. The first large-scale clinical tungsten-188/rhenium-188 generator prototype (500 mCi) was fabricated and supplied to the Center for Molecular Medicine and Immunology (CMMI), in Newark, New Jersey, for Phase I clinical trials of rhenium-188-labeled anti CEA antibodies for patient treatment. Collaborative studies are also continuing in conjunction with the Nuclear Medicine Department at the University of Massachusetts where a generator is in use to compare the biological properties of {open_quotes}direct{close_quotes} and {open_quotes}indirect{close_quotes} labeled antibodies.},
doi = {10.2172/10176496},
journal = {},
number = ,
volume = ,
place = {United States},
year = {1993},
month = {7}
}