Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

Abstract

Carcinoembryonic antigen (CEA), highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET]) have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefl y, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab', scFv, minibody, diabody and scFv-Fc) have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99m Tc-labeled anti-CEA Fab' fragment) has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99m Tc) are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111 In) are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting effi cacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to "personalized medicine".

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

“…Both SPECT and PET-labeled anti-CEA T84.66 diabodies have been synthesized and evaluated in tumor-bearing mice (165,404). Of these, the 124 I-and 18 F-labeled versions gave the best images, the latter of which afforded high-contrast images as early as 1 h postinjection, with only background levels of activity detected in CEA-negative C6 tumors (44).…”

Imaging in targeted delivery of therapy to cancer

“…A study using the L19 antibody targeting the extra-domain B (EDB) of fibronectin compared three formats: a scFv fragment, a SIP and a whole IgG and demonstrated optimum kinetics with the SIP [52]. Promising results have been seen with a 123-Iodine anti-CEA minibody [53] and a 124-Iodine anti-Her2 diabody [54] using single photon emission computed tomography (SPECT) and PET respectively.…”

Fluorescent Dye Conjugates for Optical Imaging of Cancer

“…100 Normally expressed during the development of the fetal gut, it is also a well-established tumor-associated antigen in colorectal carcinoma and adenocarcinomas of the lung, breast, other gastrointestinal organs, and the ovaries. [101][102][103] Radionuclide-based imaging techniques (gamma camera, SPECT, and PET) have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically.…”