Use of Technetium Antigranulocyte Monoclonal Antibody Fab' Fragments for the Detection of Osteomyelitis

Overview

Journal Cell Biophys

Specialty Biophysics

Date 1994 Jan 1

PMID 7736546

Citations 1

Authors

S J Harwood

J G Camblin

S Hakki

M A Morrissey

D L Laven

L M Zangara

J U Patel

W B Webster Jr

R G Carroll

Affiliations

Soon will be listed here.

Abstract

Accurate early diagnosis of osteomyelitis is critical for optimal clinical management. Conventional radiology (X-rays, CT) and nuclear medicine scans (bone, gallium, and technetium/indium white blood cell [WBC]) have limitations and drawbacks. The monoclonal antibody (MAb) ImmuRAID-MN3 (Immunomedics Inc., Morris Plains, NJ), a 99m-Tc Antigranulocyte Fab' fragment, recognizes a surface glycoprotein NCA-90/95 shared by granulocytes, carcino-embryonic antigen (CEA), and meconium antigen (MA). Intravenous injection of radiolabeled MAb enables in vivo labeling of human granulocytes and targets infected lesions in the bone and throughout the body. Technetium labeled Fab' fragments rapidly clear the blood pool and high-quality images can be obtained the same day, as early as 1 h postinjection. Results at our institution on 13 patients with clinically suspected osteomyelitis of infected long bones, prostheses, and diabetic foot ulcers were compared with the surgical/bacteriological verification of the presence or absence of infection. The MAb scan showed six true positives, six true negatives, and one false negative (very low grade infection). The procedure was safe, no clinical or laboratory adverse reactions were encountered. The MAb fragments are markedly less immunogenic than whole IgG, resulting in lower induction of human antimouse antibody (HAMA) titers. No HAMA to this MAb fragment has been detected in 24 patients (data from multiple institutions). Our preliminary results suggest that 99m-Tc ImmuRAID-MN3 is highly accurate for detection of osteomyelitis. This study is part of an ongoing multiinstitutional project sponsored by Immunomedics, Inc. to evaluate the efficacy and safety of this radiopharmaceutical.

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References

Seybold K, Locher J, Coosemans C, Andres R, Schubiger P, Blauenstein P . Immunoscintigraphic localization of inflammatory lesions: clinical experience. Eur J Nucl Med. 1988; 13(11):587-93. DOI: 10.1007/BF02574774. View

Fischman A, Rubin R, Khaw B, CALLAHAN R, Wilkinson R, Keech F . Detection of acute inflammation with 111In-labeled nonspecific polyclonal IgG. Semin Nucl Med. 1988; 18(4):335-44. DOI: 10.1016/s0001-2998(88)80042-4. View

Schauwecker D . The scintigraphic diagnosis of osteomyelitis. AJR Am J Roentgenol. 1992; 158(1):9-18. DOI: 10.2214/ajr.158.1.1727365. View

Gerzof S, Oates M . Imaging techniques for infections in the surgical patient. Surg Clin North Am. 1988; 68(1):147-65. DOI: 10.1016/s0039-6109(16)44437-3. View

Becker W, Borst U, Fischbach W, Pasurka B, Schafer R, Borner W . Kinetic data of in-vivo labeled granulocytes in humans with a murine Tc-99m-labelled monoclonal antibody. Eur J Nucl Med. 1989; 15(7):361-6. DOI: 10.1007/BF00449225. View

Zlatkin M, Pathria M, Sartoris D, Resnick D . The diabetic foot. Radiol Clin North Am. 1987; 25(6):1095-105. View

Rubin R, Young L, Hansen W, Nedelman M, Wilkinson R, Nelles M . Specific and nonspecific imaging of localized Fisher immunotype 1 Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody. J Nucl Med. 1988; 29(5):651-6. View

ten Berge R, Natarajan A, Hardeman M, van Royen E, Schellekens P . Labeling with indium-111 has detrimental effects on human lymphocytes: concise communication. J Nucl Med. 1983; 24(7):615-20. View

Reuland P, Winker K, Heuchert T, Ruck P, Muller-Schauenburg W, Weller S . Detection of infection in postoperative orthopedic patients with technetium-99m-labeled monoclonal antibodies against granulocytes. J Nucl Med. 1991; 32(12):2209-14. View

10.

Thakur M, LAVENDER J, Arnot R, SILVESTER D, Segal A . Indium-111-labeled autologous leukocytes in man. J Nucl Med. 1977; 18(10):1014-21. View

11.

Buchegger F, Schreyer M, Carrel S, Mach J . Monoclonal antibodies identify a CEA crossreacting antigen of 95 kD (NCA-95) distinct in antigenicity and tissue distribution from the previously described NCA of 55 kD. Int J Cancer. 1984; 33(5):643-9. DOI: 10.1002/ijc.2910330515. View

12.

Primus F, Newell K, Blue A, Goldenberg D . Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies. Cancer Res. 1983; 43(2):686-92. View

13.

Lind P, Langsteger W, Koltringer P, Dimai H, Passl R, EBER O . Immunoscintigraphy of inflammatory processes with a technetium-99m-labeled monoclonal antigranulocyte antibody (MAb BW 250/183). J Nucl Med. 1990; 31(4):417-23. View

14.

Zakhireh B, Thakur M, Malech H, Cohen M, Gottschalk A, Root R . Indium-111-labeled human polymorphonuclear leukocytes: viability, random migration, chemotaxis, bacterial capacity, and ultrastructure. J Nucl Med. 1979; 20(7):741-7. View

15.

Roddie M, Peters A, Danpure H, Osman S, Henderson B, LAVENDER J . Inflammation: imaging with Tc-99m HMPAO-labeled leukocytes. Radiology. 1988; 166(3):767-72. DOI: 10.1148/radiology.166.3.3340775. View

16.

Vorne M, Soini I, Lantto T, Paakkinen S . Technetium-99m HM-PAO-labeled leukocytes in detection of inflammatory lesions: comparison with gallium-67 citrate. J Nucl Med. 1989; 30(8):1332-6. View

17.

Seabold J, Nepola J, Conrad G, Marsh J, Montgomery W, Bricker J . Detection of osteomyelitis at fracture nonunion sites: comparison of two scintigraphic methods. AJR Am J Roentgenol. 1989; 152(5):1021-7. DOI: 10.2214/ajr.152.5.1021. View

18.

Andres R, Schubiger P, Tiefenauer L, Seybold K, Locher J, Mach J . Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody. Eur J Nucl Med. 1988; 13(11):582-6. DOI: 10.1007/BF02574773. View

19.

Esterhai Jr J, Goll S, McCarthy K, Velchik M, Alavi A, Brighton C . Indium-111 leukocyte scintigraphic detection of subclinical osteomyelitis complicating delayed and nonunion long bone fractures: a prospective study. J Orthop Res. 1987; 5(1):1-6. DOI: 10.1002/jor.1100050102. View

20.

Alazraki N, Dries D, Datz F, Lawrence P, Greenberg E, Taylor Jr A . Value of a 24-hour image (four-phase bone scan) in assessing osteomyelitis in patients with peripheral vascular disease. J Nucl Med. 1985; 26(7):711-7. View