title: Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy.
abstract: L-6, a mouse IgG2a anti-adenocarcinoma monoclonal antibody (MoAb) with favorable immunopathology and mouse biokinetics, was evaluated for cancer radioimmunotherapy by pharmacokinetic studies in 10 patients with breast cancer. The effect of escalating the preinfused protein dose was studied in two patients at each level, using 50, 100, 150, 200 and 400 mg of unlabeled L-6 prior to a 10 mCi imaging dose of 131I L-6. Quantitative imaging, and blood and urine clearances were obtained. After the 50 mg preinfusion, rapid blood clearance and lung extraction of the radiopharmaceutical occurred immediately post injection. Greater preload amounts of L-6 were associated with an increase in the intercept of the slow phase of the blood clearance from 17 to 22% injected dose (ID) with 50 mg to 70 to 80% ID with 400 mg (P less than 0.01). Lung uptake of the radiopharmaceutical immediately post injection decreased from 15 to 19% ID (50 mg) to 6 to 8% ID (400 mg). Tumors were visualized only after larger L-6 preloads, but in these patients small chest tumors contained 0.6-1.2% ID (0.1% ID/g maximum). This study suggests that L-6 reactive sites that are readily available in the lung can be saturated, so that a subsequent dose of I-131 L-6 is delivered to the tumor. This approach provides a new strategy for developing an effective method for radioimmunotherapy using a MoAb that has some cross-reactivity. Quantitative imaging contributed to detection of the cross-reactivity and the strategy for overcoming it.
authors.affiliation: Department of Internal Medicine, University of California, Davis Medical Center, Sacramento 95816.
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: L F
authors.initials: LF
authors.lastname: O'Grady
authors.forename: D J
authors.initials: DJ
authors.lastname: Macey
authors.forename: L A
authors.initials: LA
authors.lastname: Kroger
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
authors.forename: K R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: N B
authors.initials: NB
authors.lastname: Levy
authors.forename: S L
authors.initials: SL
authors.lastname: Mills
authors.forename: I
authors.initials: I
authors.lastname: Hellstrom
authors.forename: K E
authors.initials: KE
authors.lastname: Hellstrom
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000628:therapy; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes