[Biokinetics of tumor-affinity yttrium preparations--2]. / Untersuchung zur Biokinetik tumoraffiner Yttrium-Zubereitungen--2. Teil.

After demonstrating that the application form 87Y-NTA-EDTMP-Ca is superior to the so far used citrate form of yttrium especially regarding the tumour/liver and tumour/bone ratios, the relationships between the concentrations of the components in the 87Y-NTA-EDTMP-Ca mixture and the 87Y biokinetics were investigated in tumour-bearing mice. The increase of the EDTMP and Ca2+ concentrations by several orders of magnitude caused no significant changes of tumour radioactivity but a clear radioactivity decrease in the liver, spleen and bone, respectively. The increase of the NTA concentration led also to a radioactivity decrease in all organs and tissues investigated. A significant radioactivity reduction in the tumour could be observed only after administration of rather high NTA amounts. Considerations of the tumour/background ratios depending on different compositions of the injection mixture showed the possibility of optimizing radionuclide biodistribution.

[Biokinetics of tumor-affinity yttrium preparations--Part 1]. / Untersuchungen zur Biokinetik tumoraffiner Yttrium-Zubereitungen--1. Teil.

Differences of yttrium biokinetics after application to male tumor-bearing mice of 87Y-citrate were studied in comparison to a 87Y-NTA-EDTMP-Ca mixture after variation of both the manner of application (intraperitoneal vs. intratumoral) and the tumor type (mamma carcinoma vs. melanoma). The application of 87Y as NTA-EDTMP-Ca preparation led--in comparison to the citrate form applied so far--to a similar radionuclide tumor accumulation and distinctly lower extratumoral radioactivities in liver, spleen and skeleton with clearly more favorable tumor/background ratios. Melanomas showed a significantly higher radioactivity accumulation (factor 2-3) after injection of 87Y-NTA-EDTMP-Ca than mamma carcinomas. Intratumoral application led to high initial radioactivities in the tumors. Radioactivity concentrations which are comparable with those after intraperitoneal application were achieved within 4 h after intratumoral application. The application of the EDTMP-containing mixture promises in comparison to the traditional citrate form higher radiation doses in the tumor related to the whole-body radiation exposure. The consequences for a possible tumor therapy will be further investigated.

[Long term biokinetics of 169Yb following injection as citrate, hydroxyethylethylenediaminetetraacetate and nitrilotriacetate]. / Langzeitbiokinetik des 169Yb nach Injektion als Zitrat, Hydroxyethylethylen-diamintetraazetat und Nitrilotriazetat.

169Yb complexes with known biokinetics in tumour-bearing mice up to 48 h p.i. were injected into healthy mice to study the radionuclide biodistribution in various organs and tissues for 672 h after injection, in order to obtain reliable biokinetic data in an animal model, not affected by tumour-growth, as a basis for the calculation of biological half-life and dose distribution. The results demonstrated the existence of at least two components with different biological half-lives in the organs and tissues investigated. The effective half-lives of these components decreased with increasing stability of the complexes administered. The effective half-life of the fast component was a few hours and that of the slow one between about 200 and 800 h.

[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]. / Der Einfluss von Ethylendiamintetramethylenphosphonat auf die Bioverteilung tumoraffiner Radionuklide.

It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner.

[The effect of bone-seeking metal salts on the biodistribution of tumor-seeking heavy metal complexes]. / Der Einfluss von knochenaffinen Metallsalzen auf die Bioverteilung tumoraffiner Schwermetallkomplexe.

This work attempted to overcome the problem of unwanted bone radioactivity after injection of tumour-affine heavy-metal compounds (prototype 169Yb-citrate) by pre-application of stable yttrium- and calcium-compounds into tumour-bearing mice in doses of 1 mg metal/kg body weight. The pre-application of stable yttrium and calcium resulted in a smaller bone radioactivity. The most favourable results were achieved by injecting the metal salts simultaneously at or within 5 h before the 169Yb-citrate. On the other hand a strong radioactivity increase in the RES (liver and spleen) by a factor of 2 to 4 was observed after yttrium-preapplication.

[The effect of Ca-diethylenetriamine pentaacetate on the bio-behavior of tumor-affine metal complexes]. / Der Einfluss von Ca-Diethylentriaminpentaacetat auf das Bioverhalten tumoraffiner Metallkomplexe.

The complexon CaDTPA was injected into tumour-bearing mice in concentrations of 0.05, 0.1, 0.3, and 0.6 mole/l (pH:6) 30 min after the 169Yb-injection. 100 microliters of a 0.3 M CaDTPA solution were injected at different time points (simultaneously, 2, 5, 10, 20, 30, 40 and 50 min, 1, 1.25, 1.5, 2.5 and 10 h) after 169Yb-citrate injection. The animals were killed 24 h after radionuclide administration. A strong radioactivity decrease was observable 24 h p.i. not only in blood, liver, spleen, muscle and bone but also in the tumour if CaDTPA was administered within the first 2 h after ytterbium injection. Thereafter no change in radioactivity could be achieved by DTPA. A time phase in which the Yb could be eliminated from the tissues by means of DTPA (time intervals < 2 h) was distinguishable from a time phase in which it was not attainable for DTPA (time intervals > 5 h). This indicates that the incorporation of Yb into the cells is completed after 5 h and that the metals are intracellularly bound, probably to the lysosomes. Improvements of the scintigraphic tumour detection cannot be expected from the use of complexons.