Therapy + diagnostics = theranostics
Theranostics is the combination of therapy and diagnostics. With nuclear medicine principles, theranostics offer ever more possibilities in personalized cancer treatment.
Theranostics is a medical field developed as a real targeted therapy based on the identification and display of a biological target. In nuclear medicine, theranostics includes diagnostic imaging using radiolabeled tracers to identify a biological target structure, followed by internal radiation therapy using the same tracer. This achieves a selective and targeted treatment of disease manifestations in the body.
The method is far from new and was developed more than 75 years ago using radioactive iodine (131I) for diagnostic imaging and treatment of malignant and benign thyroid diseases (1, 2). In the 1980s (131I)-metaiodobenzylguanidine ((131I)-MIBG), a noradrenaline analogue, introduced in the diagnosis and treatment of neuroblastomas (3). However, it was only with radionuclide-labeled somatostatin analogues for the diagnosis and treatment of neuroendocrine neoplasia that the field of theranostics gained momentum. Peptide receptor radionuclide therapy for neuroendocrine neoplasia has become an established treatment alternative for inoperable and metastatic disease. The treatment has a good safety profile, good disease control, increased quality of life and better survival (4, 5). From 2002 until the treatment was introduced in Norway in autumn 2019, Norwegian patients were sent to Sweden and Denmark for treatment.
The rise in theranostics will challenge current healthcare infrastructures
The success of radionuclide therapy with peptide receptor has stimulated further development of theranostics, a current example being prostate-specific membrane antigen (PSMA). PSMA-PET/CT imaging has already been established for the investigation of biochemically proven recurrence of prostate cancer. Systemic radiotherapy with (177Lu)-PSMA-617 is approved by US drug authorities in March 2022 for patients with metastatic castration-resistant prostate cancer. The approval based on results from VISION studies, a randomized phase 3 study, in which survival and progression-free survival were significantly better with treatment with (177Lu)-PSMA-617 as a supplement to standard treatment (6). In Norway, a national method assessment for PSMA radionuclide therapy is currently underway.
The rise in theranostics will challenge current healthcare infrastructures. In Germany, the Netherlands and the United States, this has resulted in the establishment of theranostic centers. In April 2022, there are joint international guidelines for the establishment of theranostic centers (7). The guidelines emphasize the importance of close interdisciplinary collaboration between clinical departments and nuclear medicine.
Much research is being done on new radionuclide treatments, and a number of theranostic tracer pairs are being tested both preclinically and clinically. Examples of this are fibroblast activating protein expressed in cancer-associated fibroblasts (8, 9) and chemokine receptor-4 in conditions such as lymphoma and multiple myeloma (10).
For effective and safe radiotherapy, individual dose calculations (dosimetry) are of central importance. It is important to avoid both under- and over-treatment and to minimize toxicity (11). For some patients this will mean that the dose should be reduced for the treatment to be safe, while for others it may mean that the dose is higher due to individual variations and expression of the biological process.
The potential in theranostics is great. In theory, it will be possible to treat all (cancer) diseases for which there is a tracer that selectively recognizes the pathological cells, but in practice there will be many technical and biological limitations that must first be clarified. Still, with the development we are seeing now, we can expect that such personalized treatment will become relevant for many patient groups in the future.
After the manuscript for this article was approved, the European Medicines Agency also approved systemic radiotherapy with (¹⁷⁷Lu)-PSMA-617.