Radiotheranostics in oncology: current challenges and emerging opportunities

• Published in: Nature reviews. Clinical oncology 2022-08, Vol.19 (8), p.534-550
• Main Authors: Bodei, Lisa, Herrmann, Ken, Schöder, Heiko, Scott, Andrew M., Lewis, Jason S.
• Format: Article
• Language: English
• Subjects: 692/4028/67/1059/153; 692/4028/67/1059/485; 692/4028/67/1059/602; Biodistribution; Cancer therapies; Dosimetry; Drug dosages; Humans; Iodine; Ligands; Medical Oncology; Medical research; Medicine; Medicine & Public Health; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - radiotherapy; Oncology; Patients; Phenotypes; Precision Medicine; Radiation; Radiation therapy; Radioisotopes; Radiopharmaceuticals - therapeutic use; Review Article; Single photon emission computed tomography; Thyroid diseases; Tumors
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/s41571-022-00652-y

Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to noninvasively investigate tumour phenotypes and evaluate functional and molecular responses to therapy, theranostics — the combination of diagnostic imaging with targeted therapy — is becoming more widely implemented. The field of radiotheranostics, which is the focus of this Review, combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from its potential to target and eliminate tumour cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. In this Review, we describe the clinical experience with established radiotheranostics as well as novel areas of research and various barriers to progress. Radiotheranostics enables the clinician to image and then target lesions using the same probe. Despite this appealing potential, interest in the field of radiotheranostics has long been constrained by a lack of expertise, high infrastructure costs and the availability of non-radioactive alternative approaches. Nonetheless, several recent successes have led to renewed research interest. In this Review, the authors summarize the current challenges and opportunities in this rapidly emerging area. Key points Radiotheranostics combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, typically with radionuclides that emit α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from the potential to target and eliminate tumour cells with minimal adverse effects owing to a mechanism of action that is distinctly different from that of most other systemic therapies. Approvals of new radiotheranostic agents such as 177 Lu-DOTATATE and 177 Lu-PSMA-617 alongside the availability of companion diagnostic agents (such as 68 Ga-DOTATATE and 68 Ga-PSMA-11, respectively) have driven a resurgence of interest in the fiel