Radioimmunoimaging with longer-lived positron-emitting radionuclides: potentials and challenges

Abstract

Radioimmunoimaging and therapy has been an area of interest for several decades. Steady progress has been made toward clinical translation of radiolabeled monoclonal antibodies for diagnosis and treatment of diseases. Tremendous advances have been made in imaging technologies such as positron emission tomography (PET). However, these advances have so far eluded routine translation into clinical radioimmunoimaging applications due to the mismatch between the short half-lives of routinely used positron-emitting radionuclides such as (18)F versus the pharmacokinetics of most intact monoclonal antibodies of interest. The lack of suitable positron-emitting radionuclides that match the pharmacokinetics of intact antibodies has generated interest in exploring the use of longer-lived positron emitters that are more suitable for radioimmunoimaging and dosimetry applications with intact monoclonal antibodies. In this review, we examine the opportunities and challenges of radioimmunoimaging with select longer-lived positron-emitting radionuclides such as (124)I, (89)Zr, and (86)Y with respect to radionuclide production, ease of radiolabeling intact antibodies, imaging characteristics, radiation dosimetry, and clinical translation potential.

Figure 1

General scheme and reagents of radio-halogenation of intact antibodies using commonly used methods (a) Chloramine-T method, (b) Bolton-hunter method, (c) Iodogen method and (d) N-succinimidyl 4-iodobenzoate based method.

Figure 2

Representative scheme of radiolabeling intact antibodies with radio-arsenic using SATA approach.

Figure 3

Selected chelating agents used for radiolabeling intact antibodies with ⁶⁴Cu.

Figure 4

Selected chelating agents used for radiolabeling intact antibodies with ⁸⁶Y/⁹⁰Y.