title: Effect of cyclophosphamide on the binding of 99mTcO-4 and 99mTc-MDP to blood cells and plasma proteins.
abstract: Since the introduction of technetium-99m (99mTc) and its rapid acceptance as a tool in nuclear medicine, very little information is available about its biological action as 99mTc-radiopharmaceuticals. We have determined if cyclophosphamide, an alkylating agent, used in oncology as a chemotherapeutic drug, modifies the binding of 99mTcO-4 and 99mTc-MDP (99mTc-methylenediphosphonic acid) to blood cells and to plasma proteins. The radiopharmaceuticals were injected intravenously (iv) into SW-55 mice (male and female, weight 25 g) and samples of plasma and blood cells were separated. Cyclophosphamide (50 micrograms) was injected iv 1 h before the radiopharmaceuticals. Samples of plasma and blood cells were also precipitated with 5% trichloroacetic acid and soluble and insoluble fractions were isolated. The following results were obtained: 1) cyclophosphamide did not alter (0.25 to 8 h) percent radioactivity of 99mTcO-4 in plasma or blood cells but increased the binding of 99mTc-MDP to blood cells; 2) cyclophosphamide did not alter (0.25 to 8 h) the binding of 99mTcO-4 in insoluble fraction of plasma and decreased (1 to 4 h) percent radioactivity of 99mTc-MDP in the insoluble fraction of plasma; 3) cyclophosphamide increased (0.25 to 4 h) percent radioactivity of 99mTcO-4 in the insoluble fraction of blood cells but did not alter the binding of 99mTc-MDP. Cyclophosphamide and/or its metabolites modified the effective half-life of these radiopharmaceuticals (to 99mTcO-4 was increased 2.3 to 3.4 h and to 99mTc-MDP was decreased 3.3 to 2.1 h) and possibly increased the permeability of blood cells to 99mTcO-4.
authors.affiliation: Instituto de Física, Universidade do Estado do Rio de Janeiro, Brasil.
authors.forename: J S
authors.initials: JS
authors.lastname: Santos
authors.forename: E F
authors.initials: EF
authors.lastname: de-Paula
authors.forename: T G
authors.initials: TG
authors.lastname: Correa
authors.forename: L C
authors.initials: LC
authors.lastname: de-Freitas
authors.forename: L M
authors.initials: LM
authors.lastname: da-Fonseca
authors.forename: B
authors.initials: B
authors.lastname: Gutfilen
authors.forename: M
authors.initials: M
authors.lastname: Bernardo-Filho
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D013670:Sodium Pertechnetate Tc 99m / Q000378:metabolism*; D013669:Technetium Tc 99m Medronate / Q000378:metabolism*
chemical_list: D000477:Alkylating Agents; D001798:Blood Proteins; D003520:Cyclophosphamide; D013670:Sodium Pertechnetate Tc 99m; D013669:Technetium Tc 99m Medronate