Modified radioantibody fragments for reduced renal uptake
AssigneeImmunomedics, Inc.
InventorsGary L. Griffiths, Hans J. Hansen, Habibe Karacay
Life of this patent
Estimating the term…
Abstract
PEG-modified-Tc-99m-radiolabeled antibody fragments are useful for radioimmunodetection of tumors and infectious lesions and display striking reductions in renal uptake and retention of radioisotope compared to non-PEG-modified fragments.
Claims16
In a method of imaging a tumor or infectious lesion, wherein a Tc-99m-radiolabeled antibody fragment that specifically binds a marker produced by or associated with a tumor or infectious lesion is injected parenterally into a patient having a tumor or infectious lesion, and the site or sites of tumor or infectious lesion are detected by external gamma camera imaging,
- the improvement wherein, prior to labeling with Tc-99m, said radiolabeled antibody fragment is conjugated to an amount of polyethylene glycol (PEG) sufficient to significantly reduce renal uptake and retention of the radiolabel compared to non-PEGylated antibody fragment.
A method of preparing an imaging agent precursor for eventual labeling with Tc-99m, comprising the steps of:
- a) reacting a F(ab).sub.2 or F(ab').sub.2 antibody fragment that specifically binds a marker produced by or associated with a tumor or infectious lesion with an activated polyethylene glycol to form PEG-F(ab).sub.2 or PEG-F(ab').sub.2 ;
- and
- b) cleaving the PEG-F(ab).sub.2 or PEG-F(ab').sub.2 with a disulfide reducing agent to form PEG-Fab-SH or PEG-Fab'-SH, for eventual labeling with Tc-99m.
A method of preparing an imaging agent precursor for eventual labeling with Tc-99m, comprising the steps of:
- a) reacting a F(ab).sub.2 or F(ab').sub.2 antibody fragment that specifically binds a marker produced by or associated with a tumor or infectious lesion with an activated polyethylene glycol to form PEG-F(ab).sub.2 or PEG-F(ab').sub.2 ;
- and
- b) thiolating said PEG-F(ab).sub.2 or PEG-F(ab').sub.2 to form PEG-F(ab).sub.2 -SH or PEG-F(ab').sub.2 -SH, for eventual labeling with Tc-99m.
A kit for use in preparing a Tc-99m-labeled imaging agent for a tumor or infectious lesion, comprising, in a single container:
- an antibody fragment having at least one free thiol group, wherein said fragment specifically binds a marker produced by or associated with a tumor or infectious lesion, said fragment being conjugated to an amount of polyethylene glycol (PEG) sufficient to significantly reduce renal uptake and retention of the PEGylated antibody fragment after radiolabeling with Tc-99m, compared to non-PEGylated Tc-99m-labeled antibody fragment;
- and
- an amount of stannous ions effective for reducing 99m-pertechnetate, the 99m-pertechnetate to be added subsequently.
Dependencies are inferred from the claim text.