Radioimmunodetection of amyloid deposits in patients with AL amyloidosis.
Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.
Wall
Jonathan S
JS
Department of Medicine,University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
Kennel
Stephen J
SJ
Stuckey
Alan C
AC
Long
Misty J
MJ
Townsend
David W
DW
Smith
Gary T
GT
Wells
Karen J
KJ
Fu
Yitong
Y
Stabin
Michael G
MG
Weiss
Deborah T
DT
Solomon
Alan
A
D000368:Aged; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D015507:Drugs, Investigational; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography; D016719:Radioimmunodetection; D014018:Tissue Distribution
D000682:Amyloid; D000911:Antibodies, Monoclonal; D015507:Drugs, Investigational; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; C518669:amyloid L, human; C485960:monoclonal antibody 11-1f4