Retention mechanism of technetium-99m-HM-PAO: intracellular reaction with glutathione

Journal Article · Thu Dec 01 04:00:00 EST 1988 · J. Cereb. Blood Flow Metab.; (United States)

DOI:https://doi.org/10.1038/jcbfm.1988.27· OSTI ID:6786234

Neirinckx, R D; Burke, J F; Harrison, R C; Forster, A M; Andersen, A R; Lassen, N A

Preparations of d,l- and meso-hexamethylpropyleneamine oxime (HM-PAO) labeled with technetium-99m were added to rat brain homogenates diluted with phosphate buffer (1:10). The conversion of d,l-HM-PAO to hydrophilic forms took place with an initial rate constant of 0.12 min-1. Incubation of the brain homogenate with 2% diethyl maleate for 5 h decreased the homogenate's measured glutathione (GSH) concentration from 160 to 16 microM and decreased the conversion rate to 0.012 min-1. Buffered aqueous solutions of glutathione rapidly converted the HM-PAO tracers to hydrophilic forms having the same chromatographic characteristics as found in the brain homogenates. The rate constant for the conversion reaction of d,l-HM-PAO in GSH aqueous solution was 208 and 317 L/mol/min in two different assay systems and for meso-HM-PAO the values were 14.7 and 23.2 L/mol/min, respectively. Rat brain has a GSH concentration of about 2.3 mM and the conversion of the d,l-HM-PAO due to GSH alone should proceed with a rate constant of 0.48 to 0.73 min-1 and be correspondingly 14-fold slower for meso-HM-PAO. In human brain, the in vivo data of Lassen et al. show a conversion rate constant of 0.80 min-1. This correspondence of values supports the notion that GSH may be important for the in vivo conversion of 99mTc-labeled HM-PAO to hydrophilic forms and may be the mechanism of trapping in brain and other cells. A kinetic model for the trapping of d,l- and meso-HM-PAO in tissue is developed that is based on data of GSH concentration in various organs.

• Research Organization: Amersham International PLC, Bucks (England)
• OSTI ID: 6786234
• Journal Information: J. Cereb. Blood Flow Metab.; (United States), Journal Name: J. Cereb. Blood Flow Metab.; (United States) Vol. 8:6; ISSN JCBMD
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD FLOW
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DRUGS
GLUTATHIONE
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOMERIC NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MATHEMATICAL MODELS
METABOLISM
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOMETALLIC COMPOUNDS
ORGANS
OXIMES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RADIOPROTECTIVE SUBSTANCES
RATS
RETENTION
RODENTS
TECHNETIUM 99
TECHNETIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES