Emerging role of radiopharmaceutical therapy in oncology - advances, challenges, and future directions

Sep 23, 2026

Radiopharmaceutical therapy reshapes cancer management through systemic, molecularly targeted delivery of ionizing radiation, complementing external beam radiotherapy for localized lesions. The radiotheranostic approach couples diagnostic imaging with treatment, enabling patient-specific target selection, individualized dosimetry, and on-treatment monitoring. Target and radioligand advances, plus optimized pharmacokinetics and biodistribution, have improved efficacy and safety, reflected in FDA approvals of 177Lu-based agents for prostate and neuroendocrine tumors. This review traces clinical evolution, surveys emerging radioligands, and addresses challenges in patient selection, dosimetry standardization, resistance, and access while outlining paths to broader integration and innovation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Historical perspectives

JNCI Cancer Spectrum, 2026, 10(3), pkag056 [https://doi.org/10.1093/jncics/pkag056](https://doi.org/10.1093/jncics/pkag056) Advance Access Publication Date: June 2, 2026 Solicited Review Emerging role of radiopharmaceutical therapy in oncology: advances, challenges, and future directions Laura Ordas, PhD1, Sean Foster, BS1, Phuc Pham, BS1, Andy Ollendorff, BS1, Varun Gnanasekar, BS1, Mahmoud Toulany, PhD1, Quaovi H. Sodji , MD, PhD1,2, 3, 􀀃 1Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States 2Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States 3William S. Middleton Veterans Hospital, Radiation Oncology, Madison, WI, United States 􀀃 Corresponding author: Quaovi Sodji, MD, PhD, Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792, United States ([qsodji@wisc.edu](qsodji@wisc.edu)) . Abstract Radiopharmaceutical therapy has transformed cancer management by enabling systemic delivery of ionizing radiation via molecularly targeted pharmaceutics, complementing external beam radiotherapy, which primarily treats localized, radiographically defined lesions. By coupling diagnostic imaging with therapy, in a “radiotheranostic” paradigm, radiopharmaceutical therapy supports patient-specific target selection, dosimetry, and on-treatment monitoring. Progress in target discovery, radioligand chemistry, and optimization of pharmacokinetics and biodistribution has improved efficacy and safety, culminating in US Food and Drug Administration approvals of [177Lu]Lu-PSMA-617 (Pluvicto) for metastatic castration-resistant prostate cancer and [177Lu]Lu-DOTATATE (Lutathera) for neuroendocrine tumors. These successes highlight radiopharmaceutical therapy’s expanding role across oncology. This review summarizes the evolution of radiopharmaceutical therapy from early clinical milestones to modern regulatory approvals, then surveys emerging radioligands directed at new molecular pathways. We also discuss strategies to enhance therapeutic response including rational combinations with DNA damage response agents such as poly(adenosine diphosphate–ribose) polymerase inhibitors or immunotherapies. Finally, we outline key challenges such as optimal patient selection, dosimetry standardization, therapeutic resistance, and access and highlight a few ways to accelerate broader clinical integration and continued innovation. Introduction Radiation therapy is used in more than half of all cancer patients for curative intent or symptom palliation, making it a cornerstone of oncologic care.1 Radiation therapy is mostly delivered either as external beam radiation therapy via x-rays, proton, and electron or via temporary implanted radioactive sources as brachytherapy.2-4 External beam radiotherapy and brachytherapy are confined to the treatment of radiographically detectable disease. Furthermore, for widely metastatic disease that may require a large radiation field, the use of external beam radiotherapy is further limited by normal tissue toxicity. Radiopharmaceutical therapy has emerged as an approach to systemically deliver radiation to all sites of disease including radiographically occult lesions with potentially fewer side effects than whole-body irradiation delivered by external beam radiotherapy. Radiopharmaceutical therapy delivers radionuclides (radioactive atoms) to targeted tumor-associated antigens via small molecules, peptides, or antibodies. Once in the tumor microenvironment, the radionuclides decay, emitting radiation as α-particles, β-particles, γ rays, or Auger electrons.5-8 Often described as radiopharmaceutical-based theranostics or radiotheranostics, radiopharmaceutical therapy has emerged asa powerful tool for patient management. Theranostics combines radionuclide-based therapeutics preceded by molecular imaging and diagnostics. Clinically, using no

FAQs

What makes radiopharmaceutical therapy distinct from external beam radiotherapy?

Radiopharmaceutical therapy delivers radiation systemically to all disease sites, including radiographically occult lesions. External beam radiotherapy is mainly confined to radiographically detectable areas and can be limited by normal tissue toxicity for large metastatic fields.

How does the radiotheranostic paradigm guide treatment decisions?

Molecular imaging (such as SPECT/CT or PET/CT) determines target expression across metastatic lesions in real time. That imaging then informs delivery of a therapeutic radionuclide matched to the molecular target.

Which FDA-approved radiopharmaceutical therapies are highlighted?

The review highlights FDA approvals of [177Lu]Lu-PSMA-617 (Pluvicto) for metastatic castration-resistant prostate cancer and [177Lu]Lu-DOTATATE (Lutathera) for neuroendocrine tumors.

Sep 23, 2026

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