Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Inert coupling of IRDye800CW and zirconium-89 to monoclonal antibodies for single- or dual-mode fluorescence and PET imaging

<p>IRDye800CW and zirconium-89 (Zr-89) have very attractive properties for optical imaging and positron emission tomography (PET) imaging, respectively. Here we describe a procedure for dual labeling of mAbs with IRDye800CW and Zr-89 in a current good manufacturing practice (cGMP)-compliant way. IRDye800CW and Zr-89 are coupled inertly, without impairment of immunoreactivity and pharmacokinetics of the mAb. Organ and whole-body distribution of the final product can be assessed by optical and PET imaging, respectively. For this purpose, a minimal amount of the chelate N-succinyldesferrioxamine (N-sucDf) is first conjugated to the mAb. Next, N-sucDf-mAb is conjugated with IRDye800CW, after which the N-sucDf-mAb-IRDye800CW is labeled with Zr-89. After each of these three steps, the product is purified by gel filtration. The sequence of this process avoids unnecessary radiation exposure to personnel and takes about 5 h. The process can be scaled up by the production of large batches of premodified mAbs that can be dispensed and stored until they are labeled with Zr-89.</p>

Immunoglobulins as Radiopharmaceutical Vectors

With the introduction of the magic bullet concept by Ehrlich and the subsequent development of hybridoma technology by Kohler and Milstein, the world of target-specific protein-based drugs was opened. Since then, numerous immunoglobulins and a few dozen radioimmunoconjugates have been approved by the US Food and Drug Administration (US FDA) and the European Medicines Agency (EMA). In this chapter, we will discuss the array of natural and engineered immunoglobulins that are available as vectors for imaging and therapy as well as their in vivo modes of action. Several critical aspects of the accessibility and expression of targets related to the use of radioimmunoconjugates for imaging and therapy will be also discussed. These two introductory sections are followed by the core of the chapter in which we address the selection of appropriate radionuclide-immunoglobulin combinations, the possible applications of immunoPET and immunoSPECT, and how radiolabeled immunoglobulins can be evaluated