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Title: In vivo generator for radioimmunotherapy

Abstract

The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

Inventors:
; ;
Issue Date:
Research Org.:
United States Of America, Department Of Energy
Sponsoring Org.:
USDOE
OSTI Identifier:
1176586
Patent Number(s):
H000545
Assignee:
United States Of America, Department Of Energy OSTI
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 60 APPLIED LIFE SCIENCES

Citation Formats

Mausner, Leonard F., Srivastava, Suresh G., and Straub, Rita F. In vivo generator for radioimmunotherapy. United States: N. p., 1988. Web.
Mausner, Leonard F., Srivastava, Suresh G., & Straub, Rita F. In vivo generator for radioimmunotherapy. United States.
Mausner, Leonard F., Srivastava, Suresh G., and Straub, Rita F. Tue . "In vivo generator for radioimmunotherapy". United States. https://www.osti.gov/servlets/purl/1176586.
@article{osti_1176586,
title = {In vivo generator for radioimmunotherapy},
author = {Mausner, Leonard F. and Srivastava, Suresh G. and Straub, Rita F.},
abstractNote = {The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {1988},
month = {11}
}

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