Technetium-99m labeled peptides for imaging inflammation

Details Technetium-99m labeled peptides for imaging inflammation Technetium-99m labeled peptides for imaging inflammation

1994-10-11

1999-11-23

Dees, Jose' G.

Drug, bio-affecting and body treating compositions

Radionuclide or intended radionuclide containing; adjuvant...

In an organic compound

424 111, 424 165, 534 14, 530300, A61K 5100, A61M 3614

Patent

active

059895195

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
This invention relates to radiodiagnostic agents and reagents for preparing such agents, and also methods for producing radiolabeled radiodiagnostic agents. Specifically, the invention relates to technetium-99m (Tc-99m) labeled agents, methods and kits for making such agents, and methods for using such agents to image sites of infection and inflammation in a mammalian body.
2. Description of the Prior Art
A variety of radionuclides are known to be useful for radioimaging, including .sup.67 Ga, .sup.99m Tc (Tc-99m), .sup.111 In, .sup.123 I, .sup.125 I, .sup.169 Yb or .sup.186 Re. The sensitivity of imaging methods using radioactively-labeled peptides is much higher than other techniques known in the art, since the specific binding of the radioactive peptide concentrates the radioactive signal over the area of interest, for example, an inflammatory site.
There is a clinical need to be able to determine the location and/or extent of sites of focal or localized infection. In a substantial number of cases conventional methods of diagnosis (such as physical examination, x-ray, CT and ultrasonography) fail to identify such sites (e.g., an abscess). In some cases, biopsy may be resorted to, but is preferably avoided at least until it is necessary in order to identify the pathogen responsible for an abscess at a known location. Identifying the site of such "occult" infection is important because rapid localization of the problem is critical to effective therapeutic intervention.
In the field of nuclear medicine, certain pathological conditions can be localized or the extent of such conditions determined by imaging the internal distribution of administered radioactively-labeled tracer compounds (i.e. radiotracers or radiopharmaceuticals) that accumulate specifically at the pathological site. However, an abscess may be caused by any one of many possible pathogens, so that a radiotracer specific for a particular pathogen would have limited scope. On the other hand, infection is almost invariably accompanied by inflammation, which is a general response of the body to tissue injury. Therefore, a radiotracer specific for sites of inflammation would be expected to be useful in localizing sites of infection caused by any pathogen.
One of the main phenomena associated with inflammation is the location of leukocytes (white blood cells), usually monocytes and neutrophils, at the site of inflammation. A radiotracer specific for leukocytes would be useful in detecting leukocytes at the site of a localized infection. Currently approved nuclear medicine procedures for imaging sites of infection use either indium-111 labeled leukocytes (.sup.111 In-WBC) (see, e.g. Peters, 1992, J. Nucl. Med. 33: 65-67) or gallium-67 (.sup.67 Ga) citrate (see, e.g. Ebright et al., 1982, Arch. Int. Med. 142: 246-254).
A major disadvantage of using .sup.111 In-labeled WBCs is that the preparation of the radiotracer requires sterile removal of autologous blood, sterile isolation of the leukocytes from the blood, sterile labeling of the leukocytes using conditions that do not damage the cells (since damaged WBC are taken up by the reticuloendothelial system when re-injected) and return (re-injection) of the (now labeled) leukocytes to the patient. Furthermore, a delay of 12 to 48 hours between injection and imaging may be required for optimal images. While Tc-99m labeled leukocytes have been used to shorten this delay period (see, e.g. Vorne et al., 1989, J. Nucl. Med. 30: 1332-1336), ex-corporeal labeling is still required. A preferred radiotracer would be one that does not require removal and manipulation of autologous blood components.
.sup.67 Ga-citrate can be administered by intravenous injection. However, this compound is not specific for sites of infection or inflammation. Moreover, a delay of up to 72 hours is often required between injection of the radiotracer and imaging. In addition, the .gamma.-(gamma) emission energies of .sup.67 Ga are not well suited to conventional gamma cameras.
Ra

REFERENCES:
patent: 4986979 (1991-01-01), Morgan, Jr. et al.
patent: 4988496 (1991-01-01), Srinivasan et al.
patent: 5277892 (1994-01-01), Rhodes
patent: 5376356 (1994-12-01), Morgan, Jr.
patent: 5443815 (1995-08-01), Dean et al.
patent: 5508020 (1996-04-01), Dean et al.
patent: 5720934 (1998-02-01), Dean et al.
patent: 5759515 (1998-06-01), Rhodes et al.
Moyer et al (1996), J. Nucl. Med, vol. 37, No. 4, pp. 673-679, "Technetium-99m White Blood Cell Specific Imaging Agent Developed from Platelet Factor & to Detect Infection."
Zoghbi et al., 1981, "Selective cell labeling: a potential radioactive agent for labeling human neutrophils", J. Nucl. Med. 22: 32 (Abst).
Jiang et al., 1982, "Localization of abscess with an iodinated synthetic chemotactic peptide", Nuklearmedizin 21: 110-113.
Ebright et al., 1982, "The gallium scan: Problems and misuse in examination of patients with suspected infection", Arch. Int. Med. 142: 246-254.
Brenner et al., 1984, "Synthesis and Characterization of a Series of Isomeric Oxotechnetium (V) Diamido Dithiolates", Inorg. Chem. 23: 3793-3797.
Epps et al., 1987, "Brain Imaging Agents: Synthesis and Characterization of (N-Piperidinylethyl) Hexamethyl Diaminoditholate Oxo Technetium (V) Complexes" Appl. Radiat. Isot. 38: 661-664.
Wilkinson, 1988, "Chemotactic factors: an overview", Meth. Enzymol. 162: 127-132.
Tam, 1968, "Synthetic peptide vaccine design: Synthesis and properties of a high-density multiple antigenic peptide system", Proc. Natl. Acad. Sci. USA 85: 5409-5413.
Fritzberg et al., 1988, "Specific and stable labeling of antibodies with technetium-99m with a diamide dithiolate chelating agent", Proc. Natl. Acad. Sci. USA 85: 4025-4029.
Harlow & Lane, 1988, "Chapter: Immunizations", in The Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., pp. 53-137.
Vorne et al., 1989, "Technetium-99m HM-PAO-labeled leukocytes in detection of inflammatory lesions: Comparison with gallium-67 citrate", J. Nucl. Med. 30: 1332-1336.
LaMuraglia et al., 1989, "Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection", J. Vasc. Surg. 10: 20-28.
Lind et al., 1990, "Immunoscintigraphy of inflammatory processes with a technetium-99m-labeled monoclonal antigranulocyte antibody (MAb BW 250/183)", J. Nucl. Med. 31: 417-473.
Baidoo & Lever, 1990, "Synthesis of a Diaminedithiol Bifunctional Chelating Agent for Incorporation of Technetium-99m into Biomolecules", Bioconjugate Chem. 1: 132-137.
Bryson et al., 1990, "Protecting Groups in the Preparation of Thiolate Complexes of Technetium", Inorganic Chem. 29: 2948-2951.
Fischman et al., 1991, "Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs", J. Nucl. Med. 32: 482-491.
Peters, 1992, "Imaging Inflammation: Current role of labeled autologous leukocytes", J. Nucl. Med. 33: 65-67.
Najifi et al., 1992, "The Evaluation of .sup.186 Re-labeled Antibodies Using N.sub.2 S.sub.4 Chelate In Vitro and in Vivo Using Tumor-bearing Nude Mice", Nucl. Med. Biol. 19: 205-212.

Affiliated with

Also associated with

Rating

Technetium-99m labeled peptides for imaging inflammation does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Technetium-99m labeled peptides for imaging inflammation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Technetium-99m labeled peptides for imaging inflammation will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1217902