Effects of ligand structure on the lipophilicity and biodistribution of Tc-99m-amine oxime chelates

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6575373

Volkert, W A; McKenzie, E; Hoffman, T J; Troutnert, D E; Holmes, R A

Propylene amine oxime (PnAO) or 3,3'-(1-3-propanediyl-diimino) bis(3-methyl-2-butanone) dioxime, forms a neutral-lipid soluble Tc-99m-chelate in aqueous solutions. When injected it efficiently crosses the intact normal blood-brain-barrier (BBB) with approximately 80% extracted on first transit in baboon brain at normal cerebral blood flow (50 ml/min/100g). In this study the authors evaluated the effects of altered ligand structure (backbone) on the physical properties and biodistribution of several different Tc-99m amine oxime chelates in rodents. Three analogues of PnAO were evaluated: ethyleneamine oxime (EnAO), butylene-amine (BnAO), and amine oxime (AO). Each formed a neutral Tc-99m complex, determined by electrophoresis. Their octanol/saline partition coefficients were distinctly different with Tc-99m-BnAO (0.49 +- 0.09) and Tc-99m-AO (0.07 +- 0.02) being significantly less than Tc-99m-PnAO (44.3 +- 4.9). It was not possible to prepare Tc-99m-EnAO in aqueous solution as a single chemical species but when the complex was injected into rats it localized in normal brain almost identical to Tc-99m-PnAO. Both Tc-99m-AO and Tc-99m-BnAO failed to exhibit any detectable brain uptake and were both rapidly excreted through the kidneys and liver. These results show that slight structural modifications of the ligand backbone can significantly alter chelate lipid solubility and brain extraction. This infers that Tc-99m-AO and - BnAO have complex structures that are distinctly different from Tc-99m-PnAO and -EnAO.

• Research Organization: Departments of Radiology and Chemistry, Univ. of Missouri, Columbia, MO
• OSTI ID: 6575373
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

Related Subjects

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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
AQUEOUS SOLUTIONS
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BLOOD FLOW
BLOOD-BRAIN BARRIER
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHELATES
CHEMICAL PREPARATION
CHEMISTRY
CLEARANCE
COMPLEXES
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISPERSIONS
DISTRIBUTION
DRUGS
EVALUATION
EXCRETION
FUNCTIONS
HYDROXY COMPOUNDS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MIXTURES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIMES
RADIOISOTOPE SCANNING
RADIOPHARMACEUTICALS
REACTION KINETICS
RETENTION FUNCTIONS
SCINTISCANNING
SOLUTIONS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TISSUE DISTRIBUTION
UPTAKE