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Title: Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

Abstract

The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.

Authors:
Publication Date:
Research Org.:
Duke Univ., Durham, NC (United States). Medical Center
Sponsoring Org.:
USDOE Office of Energy Research, Washington, DC (United States)
OSTI Identifier:
453480
Report Number(s):
DOE/ER/60789-7
ON: DE97003642; TRN: 97:006758
DOE Contract Number:
FG05-89ER60789
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: Feb 1997
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; POSITRON COMPUTED TOMOGRAPHY; MONOCLONAL ANTIBODIES; PROGRESS REPORT; NEOPLASMS; RADIOIMMUNOTHERAPY; RADIOPHARMACEUTICALS; RADIONUCLIDE KINETICS; HYPERTHERMIA; FLUORINE 18; DOGS; MICE; RATS; LABELLING; DIAGNOSIS

Citation Formats

Zalutsky, M.R.. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995. United States: N. p., 1997. Web. doi:10.2172/453480.
Zalutsky, M.R.. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995. United States. doi:10.2172/453480.
Zalutsky, M.R.. Sat . "Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995". United States. doi:10.2172/453480. https://www.osti.gov/servlets/purl/453480.
@article{osti_453480,
title = {Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995},
author = {Zalutsky, M.R.},
abstractNote = {The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.},
doi = {10.2172/453480},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Sat Feb 01 00:00:00 EST 1997},
month = {Sat Feb 01 00:00:00 EST 1997}
}

Technical Report:

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  • This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.
  • The overall goal of this project is to be able to combine the molecular specificity of monoclonal antibodies with the imaging advantages of positron emission tomography. During the past year, were have made progress in a number of areas. This report will focus on our studies evaluating the potential of two different methods for labeling a monoclonal antibody fragment with positron-emitting F-18 both in vitro and in athymic mice bearing subcutaneous D-54 MG human glioma xenografts. The F (a b{prime}){sub 2} fragment of Me1-14, a murine egg{sub 2a} reactive with an epitope of the tumor associated proteoglycan sulfate present inmore » gliomas and melanomas, was used. This antibody is a particular interest because of our ongoing clinical radioimmunotherapy trails using Me1--14 that could ultimately benefit from the determination of quantitative dosimetry using monoclonal antibody PET imaging. Our results demonstrated, for the first time, that MAb fragments could be labeled with F-18 with retention of immunoreactivity and affinity. Further, they show that selective and specific tumor uptake of an F-18 labeled MAb fragment can be achieved in a xenograft model in a time frame compatible with the short half life of this nuclide.« less
  • The overall objective of this research project is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Both diagnostic and therapeutic applications of labeled MAbs could be improved as a result of knowledge obtained through the exploitation of the advantageous imaging characteristics associated with PET. By labeling MAbs with positron-emitting nuclides, it should be possible to quantitate the dynamics of their three-dimensional distribution in vivo. Our long-term goals are to apply this approach. 3 tabs.
  • The overall objective for this research project is to develop methods for utilizing Positron Emission Tomography (PET) to increase the clinical potential of radiolabelled monoclonal antibodies (MAbs). By labeling MAbs with positron-emitting nuclides, it should be possible to quantitate the dynamics of their three-dimensional distribution in vivo. Our long term goals are to apply this approach to investigate the following: normal tissue toxicity; radiation dose to the tumor; and early tumor imaging. The research plans of this proposal include the following specific aims: optimize labeling of MAbs with fluorine 18, bromine 76 and bromine 75; label MAb Mel-14 (reactive againstmore » human gliomas and melanomas) and its Fab and F(ab{prime}){sub 2} fragments while retaining immunoreactivity; determine the distribution of Mel-14 in athymic mice bearing human gliomas; determine pharmacokinetics of Mel-14 in nonhuman primates. Experiments with another MAb, TP-1, and iodine 124 and 131 are also planned. 8 figs.« less
  • This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.