The influence of EDTMP-concentration on the biodistribution of radio-lanthanides and 225-Ac in tumor-bearing mice

Abstract

Subitted to Nuclear Medicine and Biology 1996 OCR Output (IS 330 and IS 331) therapy using EDTMP as ligands close control of ligand concentration will be necessary.for 100 pl injected volume for the animal model used in this experiment. In radionuclide concentrations, giving highest tumor to liver ratios of enrichment, were between 1 and 10 mM reaching values close to 10 for Tm, 3 for Sm and 1 for Ac. The optimal EDTMP in tumor to that concentrated in liver are strongly influenced by the EDTMP concentration, radio-lanthanides was confirmed for all tracers used. The ratios of radioactivity concentrated methylenephosphonic acid). The strong dependence of liver uptake on the ionic radius of the solutions containing different concentrations of EDTMP (EDTMP = ethylenediaminetetra 7Tm) and 225Ac in tumor bearing nude mice. Mixtures of the radio-tracers were injected in 16 biodisuibution of carrier-free radionuclides of several lanthanides ( 141Ce, 145Sm, 149Gd, High resolution gamma spectroscopy was applied to measure simultaneously the studies. In addition to the rare earth elements 225Ac was taken into the experimental series because of its rare earth element to the next without having to change the chelator, a great advantage for optimization properties from one element to the next. In contrast to most radioisotope work, one can move from one Rare earth elements are most suitable for such studies since they show a fine graduation of chemical radio-lanthanides, and could help to design more efficient radiopharmaceuticals for diagnosis and therapy. contribute to our currently incomplete understanding on mechanisms for the tumor accumulation of the radionuclide, complex formation stability) and bio-distribution. Such information is required to to evaluate relationships between physico-chemical parameters of the injected compound (ionic radius of of our study is, rather than further collection of data on radio-tracer accumulation expressed in %/g tissue, demonstrated that EDTMP reduces significantly the liver uptake of radiolanthanides ( 5, 12, 16 ). The aim containing ligand EDTMP would favour bone uptake of Sm ( 12 ). On the other hand it has been clearly In the present study we have chosen EDTMP as the ligand. It is assumed that, as a phosphonic acid hypertonic concentrations not applicable in practice (4 ). significant influence as well. In the case of citrate we could see such an concentration effect only at for the biological behavior the overall concentration of the low molecular weight chelators must have a ligands and consequently the stability constants of the complexed ions formed play a such important role the rare earth elements are rapidly excreted via the kidney and are consequently lost. Since the chelating ( 18, 19 ). However, when injected in combination with chelating ligands forming very stable complexes ligands like or-HIB (ot-hydroxyisobutyric acid) or NTA (nitrilitriacetic acid) showed promising results species in the liver and consequently help to improve the tumor to liver ratios, and indeed...

Chelating agents for radiolanthanides: Applications to imaging and therapy

“…3 Beyer et al have described the influence of EDTMP levels on the biodistribution of 141 Ce, 145 Sm, 149 Gd, 167 Tm and 225 Ac. 38 It was found that, for liver uptake, there was a strong dependence on the ionic radii of the ligand-free cation in question, with 141 Ce and 225 Ac displaying the greatest hepatic concentration, whilst the uptake of 167 Tm was an order of magnitude less.…”

Realizing the potential of the Actinium-225 radionuclide generator in targeted alpha particle therapy applications

“…The influence of varying ethylenediamine-tetramethylenephosphonic acid (EDTMP) solution concentrations on the biodistribution of 225 Ac and radiolanthanides was determined in tumor-bearing mice [34]. Female Swiss nu/nu mice were implanted with subcutaneous T380 human colon carcinoma and injected intraveneously via the tail vein with approximately 50 kBq 225 Ac (1350 nCi) in formulations varying the concentration of EDTMP (0, 0.01, 0.05, 0.1, 0.2, 0.5, 1, 2, 10 and 30 mM) or in a 1 mM citrate control solution, adjusted to pH 6.5.…”

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

“…From earlier studies we have learnt that once the lanthanides are trapped in a tissue, like liver or bone, they are fixed quite stably [20,21]. The blood clearance for free radio-lanthanides or radio-lanthanides injected in solutions containing chelate ligands (citrate, EDTMP, NTA, EDTA, DTPA and others) is fast (half-time <1 h) [21,22]. The radio-lanthanides are then present mainly in the bone matrix and the liver, with the liver uptake determined by the ionic radius of the lanthanide [21,22,23].…”