Radioimmunotherapy for delivery of cytotoxic radioisotopes: current status and challenges

ABSTRACT

Introduction: Radioimmunotherapy (RIT) with monoclonal antibodies and their fragments labelled with radionuclides emitting α -particles, β-particles or Auger electrons have been used for many years in the development of anticancer strategies. While RIT has resulted in approved radiopharmaceuticals for the treatment of hematological malignancies, its use in solid tumors still remains challenging.

Areas covered: In this review, we discuss the exciting progress towards elucidating the potential of current and novel radioimmunoconjugates and address the challenges for translation into clinical practice.

Expert opinion: There are still technical and logistical challenges associated with the use of RIT in routine clinical practice, including development of novel and more specific targeting moieties, broader access α to α-emitters and better tailoring of pre-targeting approaches. Moreover, improved understanding of the heterogeneous nature of solid tumors and the critical role of tumor microenvironments will help to optimize clinical response to RIT by delivering sufficient radiation doses to even more radioresistant tumor cells.

KEYWORDS:

• Radioimmotherapy
• radionuclide therapy
• targeted radionuclide therapy
• monoclonal antibody

Article highlights

• Systemic radiotherapy with radiolabeled immunoconjugates delivers a non-uniform, low dose rate irradiation over a prolonged period of time, in contrast to external beam radiotherapy

• The opportunity of theragnostics, i.e. quantitative imaging of antibodies labeled with PET or SPECT radionuclides to predict subsequent therapeutic effects of an antibody radiolabeled with therapeutic α or β emitting radionuclides, significantly contributes to a personalized treatment delivery

• Radioimmunotherapy is more successful in hematological cancers than in solid tumors

• The choice of the radionuclide is of pivotal importance for therapeutic efficacy and radiation-related toxicity.

• Modification of the antibody may improve the therapeutic window when tumor targeting is preserved, while blood clearance is accelerated.

• Application of bispecific monoclonal antibodies, binding to both tumor antigens and haptens, allows faster targeting of rapidly clearing radiolabeled small molecules, thereby improving the therapeutic window of radioimmunotherapy.

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Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.