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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:
 [1];  [2];  [3]
  1. (Stony Brook, NY)
  2. (Setauket, NY)
  3. (Brookhaven, NY)
Issue Date:
Research Org.:
ASSOC UNIVERSITIES INC
OSTI Identifier:
875219
Patent Number(s):
H545
Assignee:
United States of America as represented by United States (Washington, DC) BNL
DOE Contract Number:  
AC02-76CH00016
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
vivo; generator; radioimmunotherapy; involves; labeling; monoclonal; antibodies; intermediate; half-life; radionuclides; decay; shorter; daughters; desirable; energy; beta; emissions; daughter; equilibrium; parent; exert; in-situ; tumoricidal; effect; prolonged; period; localized; fashion; essentially; in-vivo; approach; circumvents; inverse; relationship; compartmental; modeling; determine; relative; distribution; dose; nuclei; target; non-target; tissues; antibody; biodistribution; data; fit; realistic; rate; constants; model; containing; tumor; blood; non-tumor; compartments; variety; simulations; systems; ba-128; cs-128; 4d; 6m; pd-112; ag-112; 9d; 192m; results; background; ratios; achievable; virtue; rapid; excretion; chemically; uptake; clearance; phases; quantitatively; demonstrates; favorable; impact; activity; faster; especially; labeled; radionuclide; comparable; monoclonal antibody; target tissue; monoclonal antibodies; prolonged period; tumor uptake; rate constant; half-life radionuclides; energy beta; beta emissions; /424/530/

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. Fri . "In vivo generator for radioimmunotherapy". United States. https://www.osti.gov/servlets/purl/875219.
@article{osti_875219,
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 = {1}
}

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