Yttrium-90-Labeled Monoclonal Antibody for Therapy: Labeling by a New Macrocyclic Bifunctional Chelating Agent

• Published in: The Journal of nuclear medicine (1978) Vol. 31; no. 4; pp. 473 - 479
• Main Authors: Deshpande, Shrikant V, DeNardo, Sally J, Kukis, David L, Moi, Min K, McCall, Michael J, DeNardo, Gerald L, Meares, Claude F
• Format: Journal Article
• Language: English
• Published: Reston, VA Soc Nuclear Med 01-04-1990; Society of Nuclear Medicine
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Chelating Agents; Contrast media. Radiopharmaceuticals; Heterocyclic Compounds; Humans; Isotope Labeling - methods; Medical sciences; Mice; Mice, Nude; Pharmacology. Drug treatments; Tissue Distribution; Yttrium Radioisotopes - therapeutic use; Human; Radiolabelling; Citrate; Immunoradiotherapy; Monoclonal antibody; Review; Technique; Radiopharmaceuticals; Radiotherapy
• EISSN: 1535-5667
• ISSN: 0161-5505

Yttrium-90 (90Y) is a promising radiometal for therapy of cancer due to its high-energy beta emission and a physical half-life of 2.67 days. Bifunctional chelating agents based on DTPA cyclic anhydride or EDTA do not form Y(III) complexes that are stable under physiologic conditions. A new macrocyclic bifunctional chelating agent based on 1,4,7,10-tetraazacylododecane-N,N',N",N"'-tetraacetic acid (DOTA) forms a stable Y(III) complex. It was converted to p-bromoacetamidobenzyl-DOTA (BAD), and conjugated to monoclonal antibody Lym-1 via 2-iminothiolane, either as the free ligand or as the 88Y chelate. Stability studies of Lym-1-2IT-BAD-88Y in human serum in vitro showed no measurable loss of Y(III) from the ligand over a 25-day period. In Raji-tumored mice, tumor uptake was 16.8% of the injected dose per gram of tissue on Day 3. The bone uptake was 2.0, 3.6, and 2.1% injected dose per gram of tissue on Day 1, 3, and 5, respectively. The biodistribution of the control 88Y-citrate demonstrated continuous increase in bone uptake from 13.8% injected dose per gram on Day 1 to 24.9% injected dose per gram on Day 4.