Reagent and method for radioimaging leukocytes

• US 4,634,586 A
• Filed: 05/21/1984
• Issued: 01/06/1987
• Est. Priority Date: 05/21/1984
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University), Regents of the University of California (University of California)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Goodwin, David A., Meares, Claude F.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US06/612,759
• Time in Patent Office: 960 Days
• Field of Search: 424/1.1, 424/9, 424/85, 760/112 B
• US Class Current: 424/1.65
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/1093 conjugates with carriers being antibodies
• CPC Class Codes: Y10S 424/806 involving IgM

Abstract

Leukocytes are radioimmunoimaged by injecting patients with an immunoreactive nonleukocidal conjugate of an anti-leukocyte antibody and a gamma-emitting radioactive metal chelate, waiting for the conjugate to localize on the leukocytes, injecting the patient with an antibody to the conjugate to clear the blood of background nonlocalized conjugate, and visualizing the leukocytes by scintillation scanning.

Claims

1. A leukocyte radioimmunoimaging reagent comprising an immunoreactive nonleukocidal conjugate of an antibody to a leukocyte membrane determinant and a bifunctional phenyl or benzyl derivatine of EDTA or DTPA chelated with a radioactive metal.

2. The reagent of claim 1 wherein the radioactive metal is ^99m Tc, ⁶⁷ Ga, ⁶⁸ Ga or ¹¹¹ In and said derivative is of the formula ##STR2## where X is a functionality that reacts with an amino acid side chain of the antibody to covalently bind the chelating agent to the antibody and R is EDTA.

3. The reagent of claim 1 wherein the antibody is a monoclonal antibody.

4. The reagent of claim 1 wherein the leukocyte is a lymphocyte or granulocyte.

5. The reagent of claim 1 wherein the leukocyte is a noncancerous human lymphocyte, the antibody is a monoclonal antibody to a nontumor-specific membrane determinant of the lymphocyte, the metal is ¹¹¹ In, and the bifunctional phenyl or benzyl derivative of EDTA or DTPA is 1-(p-bromoacetamidobenzyl) ethylenediaminetetraacetic acid.

6. A method for making leukocytes in a patient visible by radioimmunoimaging comprising injecting an effective amount of the reagent of claim 1 into the patient subcutaneously or intravenously.

7. A method of making leukocytes in a patient visible by radioimmunoimaging comprising injecting an effective amount of the reagent of claim 5 into the patient.

8. A method of making a site of expected lymphocyte concentration in a patient visible by radioimmunoimaging comprising injecting an effective amount of the reagent of claim 4 into the patient subcutaneously or intravenously at a location from which the reagent will migrate rapidly to the site.

9. The method of claim 8 wherein the site is a lymph node, an inflammation, or an absess.

10. A method of radioimaging leukocytes comprising injecting an effective amount of the reagent of claim 1 into the patient subcutaneously or intravenously, waiting until the conjugate localizes on the leukocytes of the patient, injecting into the patient'"'"'s circulation an effective amount of antibody to the conjugate that does not cross react with endogenous components of the patient'"'"'s blood, waiting for the reticuloendothial system to clear the patient'"'"'s blood of complexes of the conjugate and the antibody to the conjugate, and visualizing the patient'"'"'s leukocytes by scintillation scanning.

11. The method of claim 10 wherein the labeled serum protein is a leukocyte radioimmunoimaging reagent comprising an immunoreactive nonleukocidal conjugate of an antibody to a leukocyte membrane determinant and a radioactive metal chelate.

12. The method of claim 11 wherein the antibody to the conjugate is an IgM.

13. The method of claim 12 wherein the antibody to the conjugate is a monoclonal antibody.

14. The method of claim 11 wherein the antibody to the conjugate is to a determinant site on the antibody of the conjugate.

15. The method of claim 11 wherein the antibody to the conjugate is to a determinant site in the chelating agent of the conjugate.

16. A kit for use in radioimmunoimaging leukocytes in a patient comprising in:

(a) a first container containing conjugate of an antibody to a nontumor-specific membrane determinant of the leukocytes and a bifunctional benzyl or phenyl derivative of EDTA or DTPA; and

(b) a second container containing an antibody to the conjugate that does not cross react with endogenous components of the patient'"'"'s blood.