Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy

Sally J. Denardo, Lois F. O'Grady, Daniel J. Macey, Linda A. Kroger, Gerald L Denardo, Kathleen R. Lamborn, Norman B. Levy, Stanley L. Mills, Ingegerd Hellstrom, Karl Erik Hellstrom

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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 <0.01). Lung uptake of the radipharmaceutical 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.

Original languageEnglish (US)
Pages (from-to)621-631
Number of pages11
JournalInternational Journal of Radiation Applications and Instrumentation.
Volume18
Issue number6
DOIs
StatePublished - 1991

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Monoclonal Antibodies
Breast Neoplasms
Radioimmunotherapy
Lung
Neoplasms
Injections
Radiopharmaceuticals
Therapeutics
Catalytic Domain
Adenocarcinoma
Thorax
Pharmacokinetics
Urine
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy. / Denardo, Sally J.; O'Grady, Lois F.; Macey, Daniel J.; Kroger, Linda A.; Denardo, Gerald L; Lamborn, Kathleen R.; Levy, Norman B.; Mills, Stanley L.; Hellstrom, Ingegerd; Hellstrom, Karl Erik.

In: International Journal of Radiation Applications and Instrumentation., Vol. 18, No. 6, 1991, p. 621-631.

Research output: Contribution to journalArticle

Denardo, Sally J. ; O'Grady, Lois F. ; Macey, Daniel J. ; Kroger, Linda A. ; Denardo, Gerald L ; Lamborn, Kathleen R. ; Levy, Norman B. ; Mills, Stanley L. ; Hellstrom, Ingegerd ; Hellstrom, Karl Erik. / Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy. In: International Journal of Radiation Applications and Instrumentation. 1991 ; Vol. 18, No. 6. pp. 621-631.
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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 <0.01). Lung uptake of the radipharmaceutical 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.",
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AU - Denardo, Sally J.

AU - O'Grady, Lois F.

AU - Macey, Daniel J.

AU - Kroger, Linda A.

AU - Denardo, Gerald L

AU - Lamborn, Kathleen R.

AU - Levy, Norman B.

AU - Mills, Stanley L.

AU - Hellstrom, Ingegerd

AU - Hellstrom, Karl Erik

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N2 - 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 <0.01). Lung uptake of the radipharmaceutical 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.

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