Radioimmunotherapy: Development of an effective approach

Technical Report · Tue Jan 01 04:00:00 EST 1991

DOI:https://doi.org/10.2172/5818061· OSTI ID:5818061

DeNardo, S J

We plan to extend our success in treating B cell malignancies with {sup 131}I labeled Lym-1 by a major effort in therapy with {sup 67}Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the {sup 111}In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the {sup 111}In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N{prime},N{double prime}, N{prime}{double prime}-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of {sup 67}Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry.

• Research Organization: California Univ., Davis, CA (United States). Dept. of Internal Medicine
• Sponsoring Organization: DOE; USDOE, Washington, DC (United States)
• DOE Contract Number: FG03-84ER60233
• OSTI ID: 5818061
• Report Number(s): DOE/ER/60233-T1; ON: DE92007126
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHELATES
COMPLEXES
COPPER 67
COPPER ISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DOCUMENT TYPES
DRUGS
HOURS LIVING RADIOISOTOPES
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
IODINE 131
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MEDICINE
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
PROGRESS REPORT
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOPHARMACEUTICALS
RADIOTHERAPY
THERAPY
TOXICITY
YTTRIUM 90
YTTRIUM ISOTOPES