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A conference paper about the study that assesses the efficacy of monoclonal antibodies (MoAbs) in a dual-targeted radioimmunotherapy with α-emitting radiation is presented. The study treated a mice with human colon carcinoma xenografts with trastuzumab and bi-humanized CC49 monoclonal antibody (HuCC4ΔCH2). The HuCC4ΔCH2 binds to tumor-associated glycoprotein 72 (TAG-72), a molecular target for cancer imaging and therapy like human epidermal growth factor receptor-2 (HER-2).

A simple, non-radioactive method for the determination of ligand-to-protein ratio (L/P) for novel ligand-antibody conjugates has been developed based on an exchange equilibrium with the purple Cu(II) complex of arsenazo III. The method requires a UV/Vis spectrometer and has been verified for monoclonal antibody Herceptin conjugates of a variety of ligand modalities, including common macrocyclic compounds NOTA and TETA, and with a new bifunctional tachpyridine (1H-Pyrrole-1-butanamide,N-[4-[[(1α,3α,5α)-3,5-bis[(2-pyridinylmethyl)amino]cyclohexyl](2-pyridinylmethyl)amino]butyl]-2,5-dihydro-2,5-dioxo-(9CI)). The spectroscopically derived values for L/P were verified by titration of the ligand-antibody conjugate with 64Cu. In each case, the value obtained by UV/Vis spectroscopy matches that found by radiolabeling. The method is rapid, taking less than 30 minutes with each ligand in this study. [Copyright &y& Elsevier]

Several monoclonal antibodies are now approved for cancer therapy, such as rituximab, an anti-CD20 monoclonal antibody for the treatment of B-cell non-Hodgkin's lymphoma. Such 'naked' antibodies can recruit the body's immune effector mechanisms to kill cells expressing the target of the antibody. In recent years, the linking of radionuclides to antibodies to either augment inherent activity or to exploit the specific targeting properties of monoclonal antibodies has been a major area of development. Two radionuclide-bearing monoclonal antibody therapies have recently been approved by the US FDA, and several more are in clinical trials. Here, we discuss the development and use of radiolabelled monoclonal antibody therapies, with a focus on radiolabelled monoclonal antibodies that have been evaluated in clinical trials. [ABSTRACT FROM AUTHOR]

Investigates the compound tris(bis(trimethylsilyl)amido)samarium experimentally by X-ray crystallography and computationally by density functional theory. Trigonal pyramidal configuration; Presence of agostic interactions; Bond length; Relevance of electrostatic terms in the agostic interaction.

Examines the spin-state alteration from sterically enforced ligand rotation in bis(indenyl)chromium(II) complexes. Details of the magnetic properties of transition metal complexes; Alignment of ligands; Use of x-ray diffraction technique.

Examines the samarium (Sm)-mediated reduction of aryl nitro compounds. Use of nuclear magnetic resonance and X-ray crystallography; Conversion of aryl and alkyl nitro compounds into amine; Reaction of Sm with nitroso compounds.

Investigates the interaction of noncoordinated phosphonium diylide with heavy group metals. Relation between organometallic compounds of the heavy group two elements and ligands; Examples of group two elements; Synthesis of heavy metals.

Abstract: A simple and rapid procedure was developed for the purification of cyclotron-produced 203Pb via the 203Tl(d,2n) 203Pb reaction. A Pb(II) selective ion-exchange resin, with commercial name Pb Resin from Eichrom Technologies, Inc., was used to purify 203Pb from the cyclotron-irradiated Tl target with excellent recovery of the enriched Tl target material. The purified 203Pb was used to radiolabel the monoclonal antibody Herceptin. The in vitro and in vivo properties of the 203Pb radioimmunoconjugate were evaluated. [Copyright &y& Elsevier]

Background: Human epidermal growth factor receptor-2 (HER-2) and tumor-associated glycoprotein 72 (TAG-72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER-2, is effective in the treatment of disseminated intraperitoneal disease when labeled with (213)Bi or (212)Pb. (213)Bi-humanized CC49 monoclonal antibody (HuCC49DeltaCH2), which binds to TAG-72, inhibits the growth of subcutaneous xenografts. A next logical step to improve therapeutic benefit would be to target tumors with both molecules simultaneously.Methods: Athymic mice bearing intraperitoneal human colon carcinoma xenografts were treated with a combination of trastuzumab and HuCC49DeltaCH2 labeled with (213)Bi administered through an intraperitoneal route. The sequence of administration also was examined.Results: Before combining the 2 monoclonal antibodies, the effective doses of (213)Bi-CC49DeltaCH2 and (213)Bi-trastuzumab for the treatment of peritoneal disease were determined to be 500 muCi for each labeled antibody. Treatment with (213)Bi-HuCC49DeltaCH2 resulted in a median survival of 45 days and was comparable to the median survival achieved with (213)Bi-trastuzumab. Each combination provided greater therapeutic efficacy than either of the agents given alone. However, the greatest therapeutic benefit was achieved when (213)Bi-HuCC49DeltaCH2 and (213)Bi-trastuzumab were coinjected, and a median survival of 147 days was obtained.Conclusions: Dual targeting of 2 distinct molecules in tumors such as TAG-72 and HER-2 with alpha-particle radiation resulted in an enhanced, additive, therapeutic benefit. The authors also observed that this radioimmunotherapeutic strategy was well tolerated. [ABSTRACT FROM AUTHOR]

Abstract: Novel ligands cis-2,6-bis[N,N-bis(carboxymethyl)aminomethyl]-1-piperidineacetic acid (PIP-DTPA), cis-[(1R,11S)-6,9,15-Tris-carboxymethyl-3,6,9,15-tetraazabicyclo[9.3.1]pentadec-3-yl]-acetic acid (PIP-DOTA), cis-{2,7-bis-[bis-carboxymethyl-amino)-methyl]-azepan-1-yl}-acetic acid (AZEP-DTPA), [2-(4,7-bis-carboxymethyl-[1,4,7]triazacyclononan-1-yl-ethyl]-2-carbonylmethyl-amino]-tetraacetic acid (NETA) and [{4-carboxymethyl-7-[2-(carboxymethylamino)-ethyl]-perhydro-1,4,7-triazonin-1-yl}-acetic acid (NPTA) are investigated as potential chelators of 177Lu, 90Y, 212Pb and 213Bi for radioimmunotherapy (RIT). The new ligands are radiolabeled with 177Lu, 86/88/90Y, 203Pb and 205/6Bi, and in vitro stability and in vivo stability of the radiolabeled complexes are assessed in human serum and athymic mice, respectively. In vitro studies indicate that all radiolabeled complexes with the exception of 90Y-AZEP-DTPA are stable in serum for 5–11 days. All new ligands examined herein are found to tightly hold 177Lu in vivo. Piperidine-backboned DTPA (PIP-DTPA) complexes radiolabeled with all radioisotopes examined display excellent in vivo stability, that is, excretion without dissociation. The azepane-backboned DTPA derivative, AZEP-DTPA, appears ineffective in binding all but 177Lu in vivo. NETA and NPTA radiolabeled with 86Y or 177Lu exhibit rapid blood clearance and low organ uptakes. Significant accretion in the kidney, femur and/or liver is observed with 203Pb-labeled AZEP-DTPA, PIP-DOTA and NPTA. Both 203Pb-PIP-DOTA and 205/6Bi-PIP-DOTA result in moderate to high renal accumulation of radioactivity. NETA exhibits improved renal accumulation with respect to PIP-DOTA for 205/6Bi but also shows significant liver uptake. Of all ligands studied, only PIP-DTPA appears to effectively bind 203Pb and 205/6Bi in vivo. PIP-DTPA, PIP-DOTA, NETA and NPTA all show strong evidence of rapid blood clearance and low organ uptake for 177Lu and 90Y. Serum stability and in vivo biodistribution results suggest PIP-DTPA as a potential chelating agent with broad applicability for use in 177Lu, 90Y, 212Pb and 213Bi RIT. [Copyright &y& Elsevier]

Reports on the Pu L[sub3] x-ray near edge absorption spectra for Plutonium. Coverage for chalcogenides, chlorides, hydrates, hydroxides, nitrates, carbonates and other compounds as solids and in solution; Substitution in zirconolite, perovskite and borosilicate glass; Extension of the correlations database between the energy and shape of the spectra from the XANES with valence and site symmetry to higher order chemical effects.