title: Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.
abstract: Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.
authors.affiliation: Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York.
authors.forename: R A
authors.initials: RA
authors.lastname: Vaccarino
authors.forename: J E
authors.initials: JE
authors.lastname: Sanchez
authors.forename: L L
authors.initials: LL
authors.lastname: Johnson
authors.forename: T S
authors.initials: TS
authors.lastname: Wang
authors.forename: D W
authors.initials: DW
authors.lastname: Seldin
authors.forename: C
authors.initials: C
authors.lastname: Marboe
authors.forename: P
authors.initials: P
authors.lastname: Egbe
authors.forename: K
authors.initials: K
authors.lastname: Bhatia
authors.forename: E A
authors.initials: EA
authors.lastname: Rose
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D006084:Graft Rejection; D006321:Heart / Q000000981:diagnostic imaging*; D016027:Heart Transplantation; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D008252:Macaca fascicularis; D009218:Myosins / Q000276:immunology*; D010215:Papio; D016719:Radioimmunodetection; D013667:Technetium; D016042:Transplantation, Heterotopic
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D013667:Technetium; D009218:Myosins