RADIOLABELED BBN-RGD HETERODIMERS FOR CANCER TARGETING
First Claim
1. A composition comprising a heterodimeric probe, wherein the heterodimeric probe comprises:
- a first peptide domain comprising a moiety having the characteristic of selectively binding to an integrin;
a second peptide domain comprising a moiety having the characteristic of selectively binding to a gastrin-releasing peptide receptor;
a linker connecting the first peptide domain and the second peptide domain;
and a prosthetic group.
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Accused Products
Abstract
The present disclosure encompasses heterodimeric compositions for delivering radiolabeled and other ligands to a cell or tissue, and particularly to compositions and methods of use thereof for targeting and imaging cells and tissues expressing both an integrin and gastrin-releasing peptide receptor, in particular prostate cancer cells. The disclosure, therefore, firstly encompasses compositions that can comprise a heterodimeric probe comprising a first peptide domain comprising a moiety capable of selectively binding to an integrin; a second peptide domain comprising a moiety capable of selectively binding to a gastrin-releasing peptide receptor; a linker connecting the first peptide domain and the second peptide domain; and a prosthetic group. The first peptide domain comprises at least one tripeptide comprising the amino acid sequence of arginine-glycine-aspartate, and the second domain can be the peptide bombesin(7-14). The prosthetic group can be the fluoride isotope 18F so that the heterodimeric probe may be detected by positron emission tomography or by single photon emission computed tomography, or a metal radionuclide. The radionuclide may be attached to the probe via a chelating tether.
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Citations
50 Claims
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1. A composition comprising a heterodimeric probe, wherein the heterodimeric probe comprises:
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a first peptide domain comprising a moiety having the characteristic of selectively binding to an integrin; a second peptide domain comprising a moiety having the characteristic of selectively binding to a gastrin-releasing peptide receptor; a linker connecting the first peptide domain and the second peptide domain; and a prosthetic group. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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31. A method of identifying a cell or a population of cells expressing an integrin and a gastrin-releasing peptide receptor, comprising:
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contacting a cell or population of cells with a composition, the composition comprising a heterodimeric probe having the characteristic of selectively binding to an integrin and to a gastrin-releasing peptide receptor of a cell; allowing the heterodimeric polypeptide probe to selectively bind to at least one of an integrin and to a gastrin-releasing peptide receptor of a cell or a population of cells; and detecting the presence of the heterodimeric probe on the cell or population of cells, whereby the presence of the heterodimeric probe on the cell or population of cells indicates that the cell or population of cells has an integrin, a gastrin-releasing peptide receptor, or both an integrin and a gastrin-releasing peptide receptor thereon. - View Dependent Claims (32, 33, 34, 35, 36, 37, 38, 48)
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39. A method of imaging a tissue in an animal or human host comprising the steps of:
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administering to an animal or human host a heterodimeric probe, wherein the probe has a detectable label thereon; detecting the presence of the detectable label in the animal or human host; and identifying a tissue in the animal or human host wherein the amount of the detectable label in the tissue is greater than in other tissues of the host, thereby determining the position of a tissue binding to the heterodimeric probe within the animal or human host. - View Dependent Claims (40, 41, 42, 43, 49)
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44. A method of delivering an agent to a cell, comprising
contacting a cell or population of mammalian cells with a heterodimeric probe having the characteristic of simultaneously binding to two an integrin and to a gastrin-releasing peptide receptor, and wherein the probe further comprises an agent to be delivered to a target cell or tissue of a mammalian subject; - and
allowing the heterodimeric probe to bind to an integrin, a gastrin-releasing peptide receptor, or both an integrin and a gastrin-releasing peptide receptor, on the cell or population of mammalian cells, thereby delivering the agent to the cell or cells. - View Dependent Claims (45, 46, 47, 50)
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Specification