Radiolabeled Antibodies for Cancer Imaging and Therapy

Abstract

Radioimmunoconjugates consist of a monoclonal antibody (mAb) linked to a radionuclide. Radioimmunoconjugates as theranostics tools have been in development with success, particularly in hematological malignancies, leading to approval by the US Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma. Radioimmunotherapy (RIT) allows for reduced toxicity compared to conventional radiation therapy and enhances the efficacy of mAbs. In addition, using radiolabeled mAbs with imaging methods provides critical information on the pharmacokinetics and pharmacodynamics of therapeutic agents with direct relevance to the optimization of the dose and dosing schedule, real-time antigen quantitation, antigen heterogeneity, and dynamic antigen changes. All of these parameters are critical in predicting treatment responses and identifying patients who are most likely to benefit from treatment. Historically, RITs have been less effective in solid tumors; however, several strategies are being investigated to improve their therapeutic index, including targeting patients with minimal disease burden; using pre-targeting strategies, newer radionuclides, and improved labeling techniques; and using combined modalities and locoregional application. This review provides an overview of the radiolabeled intact antibodies currently in clinical use and those in development.

Emerging Trends in Immunotherapy for Cancer

“…A monoclonal antibody (mAb) coupled to a radionuclide is called radioimmunoconjugate [ 256 , 257 ], RICs. Unlike ADCs, they do not require cellular uptake or endocytosis to provide anti-cancer activity; instead, DNA strand breaks occur in the target cell when a mAb emitting radionuclide attaches to its targeted antigen [ 256 , 257 , 258 ]. The advantage of radioimmunotherapy (RIT) over standard radiotherapy is that it is less hazardous and improves the efficacy of mAbs [ 256 ].…”

“…Radio-immunoconjugates (RICs) have been successfully developed as theragnostic tools, with the FDA approving Ibritumomab tiuxetan (Zevalin ® ; Biogen Idec) and 131 I-tositumomab radioimmunoconjugate for the treatment of non- Hodgkin’s lymphoma. Ibritumomab tiuxetan is a yttrium-90, and Tositumomab is an iodine-131 radionuclide coupled monoclonal antibody that targets the CD20 antigen on B-cell malignancies [ 256 , 257 , 258 , 259 , 260 ]. Even though Ibritumomab and Tositumomab are the only FDA-approved RIT, many RICs have entered clinical studies for both hematological and solid cancers.…”

“…Even though Ibritumomab and Tositumomab are the only FDA-approved RIT, many RICs have entered clinical studies for both hematological and solid cancers. Other than the therapeutic usage, RICs have a wide range of applications in cancer imaging and diagnosis [ 256 , 257 , 261 ]. Currently, 37 RICs are under phase I/II/III clinical trials for the diagnosis or treatment of various human cancers [ 256 , 257 ].…”

“…Other than the therapeutic usage, RICs have a wide range of applications in cancer imaging and diagnosis [ 256 , 257 , 261 ]. Currently, 37 RICs are under phase I/II/III clinical trials for the diagnosis or treatment of various human cancers [ 256 , 257 ].…”

Antibody-Based Approaches to Target Pancreatic Tumours

“…Antibodies are versatile molecules that can be selected in vitro by phage display and used as direct blocking therapeutics for intracellular or extracellular proteins [ 9 , 10 ]. When conjugated, they can deliver a drug payload, such as antibody drug conjugate (ADC) [ 11 ] or radiolabelled antibodies, for targeted radionuclide therapy [ 12 ]. Finally, if functionalised with a fluorescent or radio-analogue moiety, mAbs can be used as an imaging agent.…”