Gert Schachschneider

Cytostatika-Konzentrationen in Organen und Tumoren: Vergleich nach intravenöser und intratumoraler Injektion

SummaryThe cytostatic drugs Chlorambucil and Bleomycin were labeled with 131I and with 57Co, respectively; Ruthenocenealdehyde-(N-methyl-N-β-chlorethyl)-hydrazone and Ruthencoene-3-phenyl-prop.1-en-3-one were labelled with the γ-emitter 103Ru.In tumor-bearing mice the elimination and organ distribution of these radioactive substances were tested after intravenous (i.v.) and intratumoral (i.t.) injection of the drugs. The organ load showed lower values after i.t. than after i.v. application, while the radioactivity concentrations in the tumor were considerably increased after i.t. injection. The integrals of the concentration-time curves showed 10–80 times higher concentrations in the tumor after i.t. compared to i.v. injection of the drugs.ZusammenfassungDie Cytostatika Chlorambucil und Bleomycin wurden mit 131J bzw. 57Co markiert, Ruthenocenaldehyd-(N-methyl-N β-chloräthyl)-hydrazo und Ruthenocen-3-phenyl-prop-1-en-3-on mit dem γ-Strahler 103Ru. Diese radioaktiven Modell-Substanzen wurden Tumor-tragenden Mäusen intravenös und intratumoral injiziert und anschließend Exkretion und Organ-Verteilung gemessen.Nach intratumoraler (i.t.) Injektion war die Konzentration im Tumor langanhaltend höher und in den übrigen Organen niedriger als nach i.v.-Injektion. Die im Zeitraum 1–24 Std post inj. dem Tumorgebiet zur Verfügung stehenden Dosen (Integration der Konzentrations-Zeit-Kurven) sind bei i.t.-Injektion 10–80 mal höher als nach i.v. Gabe.The cytostatic drugs Chlorambucil and Bleomycin were labeled with 131I and with 57Co, respectively: Ruthenocenealdehyde-(N-methyl-N-beta-chlorethyl)-hydrazone and Ruthenocene-3-phenyl-prop.1-en-3-one were labeled with the gamma emitter 103Ru. In tumor-bearing mice the elimination and organ distribution of these radioactive substances were tested after intravenous (i.v.) and intratumoral (i.t.) injection of the drugs. The organ load showed lower values after i.t. than after i.v. application, while the radioactivity concentrations in the tumor were considerably increased after i.t. injection. The integrals of the concentration-time curves showed 10--80 times higher concentrations in the tumor after i.t. compared to i.v. injection of the drugs.

Ru-labeled ruthenocenoyl-glycine: comparison of clearance with hippuran

Ruthenocenoyl-glycine (ruppuran) is a metallocene analog of iodo-labeled hippuran. After injection of 103Ru-labeled ruppuran and ruthenocenoyl-1,1′-diglycine in rabbits, measurement with external detectors revealed a very rapid accumulation in the kidneys followed by rapid excretion of the 103Ru activity. By measurement of the radioactivity concentration in plasma and urine samples collected 1–60 min after IV injection, the plasma clearance was calculated and compared with the clearance of 125I-labeled hippuran injected simultaneously. The clearance of ruppuran and ruthenocenoyl-diglycine in rabbits was found to be somewhat higher than that of hippuran. Extrapolating to man (1.73 m3), plasma clearance with both ruthenocene derivatives was approximately 500–600 ml/min. Biochemical data as well as the nuclear properties of 97Ru indicate the usefulness of 97Ru-labeled ruthenocenoyl-glycine as a radiopharmaceutical for kidney function studies.

Analoga des Hippurans: [103Ru]Ruthenocenoyl-glycin-Derivate. Synthese, Organ-Verteilung und Clearance /Analogue of Hippuran: Labelled Ruthenocenoyl-glycin. Synthesis, Organ Distribution and Clearance

The analogue of hippuric acid, ruthenocenoyl-glycine was synthesized and labelled with the γ-emitter 103Ru. As a by-product of the synthesis the labelled diamide from ruthenocene- dicarbonic acid and glycine was gained. With these ruthenocene derivatives the organ distributions in mice and rats were measured. All ruthenocene-glycine derivatives showed primary a high kidney accumulation followed by very rapid renal excretion. After application of the cytostatic PtCl2(NH3)2, causing toxic effects in the kidney of mice, the excretion of ruthenocenoyl-glycine is decreased. Biochemical data suggest the use of labelled ruthenocenoyl-glycine as a substitute for Iodo-labelled hippuran.