Development of positron emission tomography imaging by 64Cu-labeled Fab for detecting ERC/mesothelin in a mesothelioma mouse model.
BACKGROUND
Malignant mesothelioma is a highly aggressive form of cancer. Curative surgery is the only effective therapy for mesothelioma, and therefore early diagnosis is important. However, early diagnosis is difficult using current diagnostic imaging techniques, and a new imaging method for early diagnosis is urgently required. We evaluated the affinity of radiolabeled monoclonal antibodies to the C-terminal fragment of ERC/mesothelin for this purpose.


METHODS
In-labeled or I-labeled IgG against C-terminal fragment of ERC and its Fab fragment were evaluated in vitro by cell binding, competitive inhibition, and cellular internalization assays, and in vivo by biodistribution in mice bearing ERC-expressing tumors. Next, the Fab fragment was labeled with the positron emitter Cu and evaluated by positron emission tomography (PET).


RESULTS
Radiolabeled IgG and Fab showed specific binding to ERC-expressing mesothelioma cells with high affinity. Both radiolabeled IgG and Fab internalized into cells after binding to ERC on the cell surface. In-labeled IgG accumulated in ERC-expressing tumors and resulted in a moderate tumor-to-blood ratio at 4 days after injection. Furthermore, PET using Cu-labeled Fab visualized the tumor at 6 h after injection.


CONCLUSIONS
Cu-labeled Fab can be useful for ERC-specific PET imaging, and can thus facilitate improved diagnosis of patients with early-stage mesothelioma.
Yoshida
Chisato
C
Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa, Inage-ku, Japan.
Sogawa
Chizuru
C
Tsuji
Atsushi B
AB
Sudo
Hitomi
H
Sugyo
Aya
A
Uehara
Tomoya
T
Hino
Okio
O
Yoshii
Yukie
Y
Fujibayashi
Yasuhisa
Y
Fukumura
Toshimitsu
T
Koizumi
Mitsuru
M
Arano
Yasushi
Y
Saga
Tsuneo
T
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000090204:Mesothelin; D008654:Mesothelioma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*
D003301:Copper Radioisotopes; D058851:GPI-Linked Proteins; D006573:Heterocyclic Compounds, 1-Ring; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; C000715528:Msln protein, mouse; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000090204:Mesothelin