Effective treatment of established human breast tumor xenografts in immunodeficient mice with a single dose of the alpha-emitting radioisotope astatine-211 conjugated to anti-HER2/neu diabodies.

Purpose: Successful radioimmunotherapy strategies depend on selecting radioisotopes with physical properties complementary to the biological properties of the targeting vehicle. Small, engineered antitumor antibody fragments are capable of rapid, highly specific tumor targeting in immunodeficient mouse models. We hypothesized that the C6.

Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1.

CD30 is a member of the TNF receptor superfamily. Overexpression of CD30 on some neoplasms versus limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise.

The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia.

Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. alpha-Particles are very attractive for cancer therapy, especially for isolated malignant cells, as is observed in leukemia, because of their high linear energy transfer and short effective path length. We evaluated an anti-CD25 [interleukin-2 receptor alpha (IL-2R alpha)] monoclonal antibody, 7G7/B6, armed with (211)At as a potential radioimmunotherapeutic agent for CD25-expressing leukemias and lymphomas.

Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein.

Significant improvement of in vivo stability of 211At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[211At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The 211At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 degrees C for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed.

Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.

Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25.

Purification of cyclotron-produced 203Pb for labeling Herceptin.

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.

Preparation and in vivo evaluation of novel linkers for 211At labeling of proteins.

The syntheses, radiolabeling, antibody conjugation and in vivo evaluation of new linkers for (211)At labeling of monoclonal antibodies are described. Syntheses of the N-succinimidyl esters and labeling with (211)At to form succinimidyl 4-methoxymethyl-3-[(211)At]astatobenzoate (9) and succinimidyl 4-methylthiomethyl-3-[(211)At]astatobenzoate (11) from the corresponding bromo-aryl esters is reported. Previously reported succinimidyl N-{4-[(211)At]astatophenethyl}succinamate (SAPS) is employed as a standard of in vivo stability.

Pretargeted alpha emitting radioimmunotherapy using (213)Bi 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-biotin.

Purpose: The use of an alpha emitter for radioimmunotherapy has potential advantages compared with beta emitters. When administered systemically optimal targeting of intact antibodies requires >24 h, therefore limiting the use of short-lived alpha emitters. This study investigated the biodistribution of bismuth-labeled biotin in A431 tumor-bearing mice pretargeted with antibody B3-streptavidin (B3-SA) and examined the therapeutic efficacy of the alpha emitter, (213)Bi-labeled biotin.

Semi-automated 86Y purification using a three-column system.

The separation of (86)Y from (86)Sr was optimized by a semi-automated purification system involving the passage of the target sample through three sequential columns. The target material was dissolved in 4 N HNO(3) and loaded onto a Sr-selective (Sr-Spec) column to retain the (86)Sr. The yttrium was eluted with 4 N HNO(3) onto the second Y-selective (RE-Spec) column with quantitative retention.

Routine quality control of recycled target [18O]water by capillary electrophoresis and gas chromatography.

Recycling of [(18)O]water for [(18)F]fluoride production can be accomplished with reliable results. We have developed sensitive, robust, and rapid analyses of impurities in [(18)O]water. Anions were quantitated by capillary electrophoresis and organic residuals were quantitated by gas chromatography using methods with excellent reproducibility and linearity.

A new and convenient method for purification of 86Y using a Sr(II) selective resin and comparison of biodistribution of 86Y and 111In labeled Herceptin.

A simple and rapid procedure was developed for purification of cyclotron produced 86Y via the 86Sr(p,n) 86Y reaction. A commercially available Sr(II) selective resin was used to separate 86Y from the cyclotron irradiated Sr(II) target with a recovery of the enriched Sr(II) target while yielding a 75-80% recovery of 86Y suitable for radiolabeling either proteins or peptides. To demonstrate the utility of this methodology, the anti-HER2 monoclonal antibody Herceptin was radiolabeled with the purified 86Y and compared to 111In labeled Herceptin.