Some technetium complexes for labelling red blood cells
Some technetium complexes for labelling red blood cells
A new approach to produce technetium labelled red blood cells, used routinely in diagnostic nuclear medicine, is reported. The engine Carbonic Anhydrase (CA), present in erythrocytes, is strongly inhibited by primary aromatic sulphonamides, which bind at the enzyme active site. Three types of ligand able to coordinate to technetium and suitable for modification to include a primary aromatic sulphonamide group were studied: the bis(thiosemicarbazones), p-sulphonamylphenylglyoxalbis-4-(alkyl-thiosemicarbazone) (alkyl = Me(SMT), Et(SET)); the Schiff bases N- salicylaldimine-N'- (2-pyridinecarboxaldimine) -propan-l,3-diamine and N-salicylaldimine-dipropylenetriamine; and the propylene amine oximes (PAO) 3,3'- (2-methyl,2-(p-sulphonamylbenzoyl) methylamino)-l,3-propanediyldiimino-bis(3-methyl-2-butanone) dioxime (PN130) and l,3-propanediyldiimino-3- (3-methyl-2-butanone) oxime-4'- ((1-N-amido-p-benzenesulphonamide) -4-methyl-pentan-3-one)oxime (PN135).
The experimental conditions needed to label the ligands were determined. Both the thiosemicarbazone and PAO derivatives were labelled, but under no conditions attempted were the Schiff bases complexed by Technetium.
The two major isozymes of Human Carbonic Anhydrase, HCA I and HCA II, were isolated from blood. The strength of binding of the free ligands SET, PN130 and PN135 with each of the isozymes was measured and expressed as the Dissociation Constant Kj.
The rate of uptake of the technetium complexes into washed RBCs and whole blood was measured and found to be much slower in whole blood. The interaction of the technetium complexes with serum proteins was studied using serum dilution techniques.
The biodistribution of both TcPN130 and TcPN135 in rats was determined and scintigraphic images for the TcPN130 complex were recorded. These complexes were retained within the cell but the rate of uptake was slow enough to allow excretion of the unbound complex via the kidneys and liver.
Attempts to synthesise the Tc-99 analogues on the milligram scale to allow chemical characterisation of these complexes were unsuccessful.
University of Southampton
Emery, Martin Frank
eb58bf3c-a0a5-422d-8c57-5b8dac920cfa
1989
Emery, Martin Frank
eb58bf3c-a0a5-422d-8c57-5b8dac920cfa
Emery, Martin Frank
(1989)
Some technetium complexes for labelling red blood cells.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
A new approach to produce technetium labelled red blood cells, used routinely in diagnostic nuclear medicine, is reported. The engine Carbonic Anhydrase (CA), present in erythrocytes, is strongly inhibited by primary aromatic sulphonamides, which bind at the enzyme active site. Three types of ligand able to coordinate to technetium and suitable for modification to include a primary aromatic sulphonamide group were studied: the bis(thiosemicarbazones), p-sulphonamylphenylglyoxalbis-4-(alkyl-thiosemicarbazone) (alkyl = Me(SMT), Et(SET)); the Schiff bases N- salicylaldimine-N'- (2-pyridinecarboxaldimine) -propan-l,3-diamine and N-salicylaldimine-dipropylenetriamine; and the propylene amine oximes (PAO) 3,3'- (2-methyl,2-(p-sulphonamylbenzoyl) methylamino)-l,3-propanediyldiimino-bis(3-methyl-2-butanone) dioxime (PN130) and l,3-propanediyldiimino-3- (3-methyl-2-butanone) oxime-4'- ((1-N-amido-p-benzenesulphonamide) -4-methyl-pentan-3-one)oxime (PN135).
The experimental conditions needed to label the ligands were determined. Both the thiosemicarbazone and PAO derivatives were labelled, but under no conditions attempted were the Schiff bases complexed by Technetium.
The two major isozymes of Human Carbonic Anhydrase, HCA I and HCA II, were isolated from blood. The strength of binding of the free ligands SET, PN130 and PN135 with each of the isozymes was measured and expressed as the Dissociation Constant Kj.
The rate of uptake of the technetium complexes into washed RBCs and whole blood was measured and found to be much slower in whole blood. The interaction of the technetium complexes with serum proteins was studied using serum dilution techniques.
The biodistribution of both TcPN130 and TcPN135 in rats was determined and scintigraphic images for the TcPN130 complex were recorded. These complexes were retained within the cell but the rate of uptake was slow enough to allow excretion of the unbound complex via the kidneys and liver.
Attempts to synthesise the Tc-99 analogues on the milligram scale to allow chemical characterisation of these complexes were unsuccessful.
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Published date: 1989
Identifiers
Local EPrints ID: 460936
URI: http://eprints.soton.ac.uk/id/eprint/460936
PURE UUID: 199c8155-8551-4023-aed4-ce986343bbd2
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Date deposited: 04 Jul 2022 18:32
Last modified: 23 Jul 2022 00:58
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Author:
Martin Frank Emery
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