Development of a new radiolabel (lead-203) and new chelating agents for labeling monoclonal anntibodies for imaging

High liver uptake and slow body clearance presently limit the usefulness of /sup 111/In labeled antibodies for tumor imaging. We have investigated /sup 203/Pb as an alternate and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A were labeled (bicyclic anhydride method) with /sup 203/Pb and /sup 111/In with 60 and 90% labeling yields, respectively. The biodistribution of /sup 203/Pb-17-1A conjugates was compared with the corresponding /sup 111/In-labeled preparations and with /sup 203/Pb-DTPA, /sup 203/Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24, and 96 hr. Lead-203-labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared to indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2- diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium. 32 refs., 3 tabs

Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy

Production and supply of radioisotopes with high-energy particle accelerators current status and future directions

Although the production of radioisotopes in reactors or in low to medium energy cyclotrons appears to be relatively well established, especially for those isotopes that are routinely used and have a commercial market, certain isotopes can either be made only in high-energy particle accelerators or their production is more cost effective when made this way. These facilities are extremely expensive to build and operate, and isotope production is, in general, either not cost-effective or is in conflict with their primary mandate or missions which involve physics research. Isotope production using high-energy accelerators in the US, therefore, has been only an intermittent and parasitic activity. However, since a number of isotopes produced at higher energies are emerging as being potentially useful for medical and other applications, there is a renewed concern about their availability in a continuous and reliable fashion. In the US, in particular, the various aspects of the prediction and availability of radioisotopes from high-energy accelerators are presently undergoing a detailed scrutiny and review by various scientific and professional organizations as well as the Government. A number of new factors has complicated the supply/demand equation. These include considerations of cost versus needs, reliability factors, mission orientation, research and educational components, and commercial viability. This paper will focus on the present status and projected needs of radioisotope production with high-energy accelerators in the US, and will compare and examine the existing infrastructure in other countries for this purpose

Preparation of high specific activity technetium-96

The present invention relates to a method of producing Tc-96 from the proton irradiation of a rhodium target and a technique for isolating under remote hot cell conditions the Tc-96 from the proton irradiated target