Microdistribution of targeted, fluorescently labeled anti-carcinoembryonic antigen antibody in metastatic colorectal cancer: implications for radioimmunotherapy.
OBJECTIVE
Most radioimmunotherapy studies on radiolabeled antibody distribution are based on autoradiographic and radioluminographic data, which provide a lack of detailed information due to low resolution. We used fluorescently labeled anti-carcinoembryonic antigen (CEA) antibody (A5B7) to investigate quantitatively the kinetics and microdistribution of antibody in a clinically relevant orthotopic colorectal cancer model (LS174T) using high-resolution digital microscopy.


METHODS
Nude mice bearing LS174T liver orthotopic tumors received a single i.v. injection of fluorescently labeled A5B7 and were sacrificed at 10 minutes, 1 hour, or 24 hours postinjection. Before sacrifice, mice were injected with the perfusion marker Hoechst 33342. An anti-CD31 antibody was used to detect blood vessel distribution. Cryostat sections were processed with immunofluorescence procedures and analyzed with fluorescence microscopy and image analysis techniques. The fluorescence images were related to morphologic images of the same or adjacent tumor sections.


RESULTS
Fluorescently labeled antibody showed rapid, selective uptake into tumor deposits, with a strong negative correlation with tumor size at 10 minutes and 1 hour (P < or = 0.01). By 24 hours, the correlation was no longer significant. The study showed movement of antibody across the tumor with time and a tendency to localize more uniformly by later time points (24 hours). The rate of antibody motility was similar in small and large tumor metastases, but small deposits showed more rapid antibody localization. Intratumoral vessels were positively related to tumor size (P < or = 0.001).


CONCLUSIONS
The obtained data suggest that radioimmunotherapy can be highly efficient in an adjuvant or minimal residual disease setting.
Fidarova
Elena F
EF
Cancer Research UK Targeting and Imaging Group, Department of Oncology, University College London, London, United Kingdom.
El-Emir
Ethaar
E
Boxer
Geoffrey M
GM
Qureshi
Uzma
U
Dearling
Jason L J
JL
Robson
Mathew P
MP
Begent
Richard H J
RH
Trott
Klaus R
KR
Pedley
R Barbara
RB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes