High-resolution microPET imaging of carcino-embryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment

Citation
Am. Wu et al., High-resolution microPET imaging of carcino-embryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment, P NAS US, 97(15), 2000, pp. 8495-8500
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
97
Issue
15
Year of publication
2000
Pages
8495 - 8500
Database
ISI
SICI code
0027-8424(20000718)97:15<8495:HMIOCA>2.0.ZU;2-#
Abstract
Rapid imaging by antitumor antibodies has been limited by the prolonged tar geting kinetics and clearance of labeled whole antibodies. Genetically engi neered fragments with rapid access and high retention in tumor tissue combi ned with rapid blood clearance are suitable for labeling with short-lived r adionuclides, including positron-emitting isotopes for positron-emission to mography (PET). An engineered fragment was developed from the high-affinity anticarcinoembryonic antigen (CEA) monoclonal antibody T84.66. This single -chain variable fragment (Fv)-C(H)3, or minibody, was produced as a bivalen t 80 kDa dimer. The macrocyclic chelating agent 1,4,7,10-tetraazacyclododec ane-N,N',N ", N'''-tetraacetic acid (DOTA) was conjugated to the anti-CEA m inibody for labeling with copper-64, a positron-emitting radionuclide (t(1/ 2) = 12.7 h). In vivo distribution was evaluated in athymic mice bearing pa ired LS174T human colon carcinoma (CEA positive) and C6 rat glioma (CEA neg ative) xenografts. Five hours after injection with Cu-64-DOTA-minibody, mic roPET imaging showed high uptake in CEA-positive tumor (17.9% injected dose per gram +/- 3.79) compared with control tumor (6.0% injected dose per gra m +/- 1.0). In addition, significant uptake was seen in liver, with low upt ake in other tissues. Average target/background ratios relative to neighbor ing tissue were 3-4:1. Engineered antibody fragments labeled with positron- emitting isotopes such as copper-64 provide a new class of agents for PET i maging of tumors.