In vivo generator for radioimmunotherapy
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.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC02-76CH00016
- Assignee:
- The United States of America as represented by the United States Department of Energy (Washington, DC)
- Patent Number(s):
- H000545
- Application Number:
- 07/114914
- OSTI ID:
- 1176586
- Resource Relation:
- Patent File Date: 1987 Oct 30
- Country of Publication:
- United States
- Language:
- English
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