This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10(6) Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 micro g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%+/-4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%+/-2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with (149)Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach.

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...

We propose a novel method for the site-specific labeling of antibodies under mild conditions and give as an example the modification of an F(ab')2-like fragment of the chimeric monoclonal antibody B72.3. The F(ab')2-like fragment was produced by the action of the protease lysyl endopeptidase. Reverse proteolysis, catalyzed by the same enzyme, was then used to attach carbohydrazide specifically to the carboxyl termini of the heavy chains of the fragment. Finally, a radiolabeled chelator possessing an aldehyde group was conjugated to the modified fragment through a hydrazone linkage. The resulting site-specifically labeled F(ab')2-like fragment was characterized by gel electrophoresis and by enzymic digestion. It was found to possess immunoreactivity equivalent to that of the unmodified F(ab')2-like fragment as determined by immunofluorescence and ELISA (enzyme-linked immunosorbent assay) techniques. The advantages and disadvantages of this labeling method, which appear to be of quite general applicability, are discussed.

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