Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells.
BACKGROUND
Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques.


METHODS
The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 microg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining.


RESULTS
Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed.


CONCLUSIONS
This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.
Carrió
I
I
Department of Nuclear Medicine, Hospital de Sant Pau, Barcelona, Spain.
Pieri
P L
PL
Narula
J
J
Prat
L
L
Riva
P
P
Pedrini
L
L
Pretolani
E
E
Caruso
G
G
Sarti
G
G
Estorch
M
M
Berná
L
L
Riambau
V
V
Matías-Guiu
X
X
Pak
C
C
Ditlow
C
C
Chen
F
F
Khaw
B A
BA
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000000981:diagnostic imaging* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000000981:diagnostic imaging; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000276:immunology*; D011817:Rabbits; D016719:Radioimmunodetection; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015899:Tomography, Emission-Computed, Single-Photon
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D011993:Recombinant Fusion Proteins