4-[18F]Fluorobenzoyl-T84.66 diabody

Carcinoembryonic antigen (CEA) was first identified from extracts of human colon adenocarcinoma (1) and fetal gut (2). It is a β-glycoprotein, and its predominant expression on the cell surface is increased in a variety of carcinomas and in certain inflammatory states such as inflammatory bowel disease (3, 4). CEA has a molecular weight of ~180 kDa, and it can be shed and detected in the serum (5). CEA expression is observed in patients with various carcinomas of the colon, lungs, thyroid, uterus, ovaries, pancreas, and medullary thyroid (6). Radiolabeled monoclonal Antibodies (mAbs) have been developed for both the diagnosis and treatment of tumors (7, 8). ^99mTc-Arcitumomab (a murine anti-CEA mAbFab’ fragment) was approved by the United States Food and Drug Administration in 1999 for whole-body planar and single-photon emission computed tomography (SPECT) imaging of CEA expression.

Single-chain variable fragments (scFvs) of Antibodies with a molecular mass of 25 kDa are cleared very rapidly from the circulation, but they exhibit poor tumor retention because they have lower affinity than the parent antibody (9). On the Other hand, bivalent antibody fragments possess more ideal tumor-targeting characteristics, including rapid tissue penetration, high target retention, and rapid blood clearance. The diabody fragment (a dimer of scFvs; molecular mass = 55 kDa) has been evaluated for targeting in several tumor antigen systems and has demonstrated rapid tumor localization and high-contrast imaging (9, 10). In particular, a murine anti-CEA T84.66 diabody, which retains excellent CEA-binding properties, was radiolabeled with ¹²⁴I for localization of CEA-positive tumors in mice (11). However, for clinical development, ¹⁸F offers the advantages of easy availability, a higher positron yield (nearly 100% versus 23% for ¹²⁴I), and a short half-life (109.7 min versus 4.18 days for ¹²⁴I). Therefore, a diabody labeled with ¹⁸F is more suitable for routine clinical use because of the biological targeting and clearance kinetics of diabodies. 4-[¹⁸F]Fluorobenzoyl-T84.66 diabody ([¹⁸F]FB-T84.66 diabody) is being developed as a positron emission tomography (PET) agent to image CEA-expressing tumors.