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

Conference · Fri Jan 01 04:00:00 EST 1988

OSTI ID:6419797

Srivastava, S C; Mease, R C; Meinken, G E; Mausner, L F; Steplewski, Z

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.

• Research Organization: Brookhaven National Lab., Upton, NY (USA)
• DOE Contract Number: AC02-76CH00016
• OSTI ID: 6419797
• Report Number(s): BNL-41800; CONF-8805211-3; ON: DE89009530
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BETA DECAY RADIOISOTOPES
BODY
CHELATING AGENTS
CHEMICAL PREPARATION
CHEMISTRY
COMPUTERIZED TOMOGRAPHY
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
GASTROINTESTINAL TRACT
HEAVY NUCLEI
INTESTINES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LARGE INTESTINE
LEAD 203
LEAD ISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
OPTIMIZATION
ORGANS
POSITRON COMPUTED TOMOGRAPHY
RADIOCHEMISTRY
RADIOISOTOPES
RADIOPHARMACEUTICALS
SECONDS LIVING RADIOISOTOPES
SYNTHESIS
TOMOGRAPHY