Novel radioiodinated neuroreceptor ligands

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1993

OSTI ID:7044090

Musachio, J L

Since many bioactive compounds do not readily undergo direct labeling with radioisotopes of iodine, the novel prosthetic groups, p-toluenesulfonate esters of (E)- and (Z)-3-(tri-n-butylstannyl)prop-2-en-1-ol, were designed to complement existing methods for radioiodine incorporation. The preparation and synthetic utility of these bifunctional reagents are described. These vinylstannylated alkylating agents were coupled with nucleophilic functionalities (amide nitrogen, secondary amine, tertiary alcohol) in acceptable to excellent yields. Regio- and stereospecific radioiododestannylation with retention of configuration occurred under mild, no-carrier-added conditions to give the corresponding radiolabeled N- or O-iodoallyl analogs in good radiochemical yields with high specific radioactivities. The methodology is versatile and well-suited to selective labeling of small molecules with radioisotopes of iodine. Of particular importance are the N-iodoallyl analogs of spiperone and the O-iodoallyl analog of diprenorphine for in vitro and in vivo studies of dopamine D[sub 2] and opioid receptors. For in vivo studies of central serotonin 5-HT[sub 2] receptors via single photon emission computed tomography (SPECT), novel radioiodinated N1-alkyl-2-iodo-LSD derivatives were synthesized. These target radioligands were prepared in moderate radiochemical yields. D-(+)-N1-ethyl-2-iodo-LSD, EIL, was identified as the most promising candidate of this series. [[sup 125]I]-EIL binds to central 5-HT[sub 2] receptors with high affinity and selectivity in vitro and labels 5-HT[sub 2] receptors in vivo with high specificity. For preparation of EIL labeled with [sup 123]I, an optimized procedure was developed that gave [[sup 123]I]-EIL in acceptable yields. This radioligand allowed visualization of serotonin 5-HT[sub 2] sites in living baboon brain via SPECT. [[sup 123]I]-EIL may serve as an agent for tomographic studies of human cerebral 5-HT[sub 2] receptors in normal and disease states.

• Research Organization: Johns Hopkins Univ., Baltimore, MD (United States)
• OSTI ID: 7044090
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400703* -- Radiochemistry & Nuclear Chemistry-- Radioisotope Production
550201 -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATED AROMATICS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
CHEMICAL REACTIONS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
HOURS LIVING RADIOISOTOPES
HYDROCARBONS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 123
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLING
LIGANDS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIOCHEMISTRY
RADIOISOTOPES
SULFONIC ACID ESTERS
TIN COMPOUNDS
TOLUENE