Interventional radiology is an essential player in modern clinical oncology practice—almost all tumor boards nowadays have a seat reserved for IR. As a physician trained in both interventional radiology and nuclear medicine, I believe we have reached a point where IRs need to be well informed about radiotheranostics and potential IR opportunities as we move towards intra-arterial radiotheranostic therapies in the future.
What is radiotheranostics?
Radiotheranostics is a platform that combines the diagnostic and therapeutic aspects of oncology practice into one paradigm. In radiotheranostics, a chemically sophisticated ligand is designed to attach to tumor-specific receptors. When the ligand is linked to a diagnostic radionuclide, a high-quality diagnostic scan is produced that accurately maps the sites of active disease and the density of tumor-specific receptors. When the same ligand is linked to a therapeutic radionuclide, the resultant radiopharmaceutical attacks the same receptors with high accuracy resulting in highly selective therapeutic effect.
The two common clinical applications of radiotheranostics nowadays are the use of Lutathera for treatment of gastroenteropancreatic neuroendocrine tumors (GEP NETs) and the use of Pluvicto for treatment of castration-resistant metastatic prostate cancer. Taking NETs as an example, gallium-68 DOTATATE (Ga DOTATATE) is commonly performed first to check the extent of the disease and to evaluate the presence of sufficient receptor density to proceed with the treatment. If the scan is favorable, treatment with Lutathera is then started. Treatment is in the form of intravenous infusions; usually four sessions with 8-week intervals between sessions.
How I learned about radiotheranostics
I first discovered radiotheranostics in my radiology residency at the University of Iowa, which is a big hub of nuclear medicine. During one of the nuclear medicine lectures, the speaker talked about radiotheranostics as one of the emerging fields of nuclear medicine. At that time, this field was in early clinical practice.
As someone interested in interventional oncology, I was impressed by the advantages that radiotheranostics can bring to the field of oncology. It did not take me long to decide I wanted to do a nuclear medicine fellowship, specifically, to learn more about radiotheranostics.
This led me to complete a nuclear medicine fellowship at the University of Iowa, followed by an interventional radiology fellowship at Harvard-BIDMC in Boston. I am currently a clinical assistant professor at the Medical College of Georgia, Augusta University, the medical director of the theranostics program and the program director of the integrated IR/DR residency.
The intersection of IR and radiotheranostics
IR introduced revolutionary treatment options to the field of medical oncology. The transarterial approach allowed for selective delivery of chemotherapy and radiation to tumors, resulting in increased drug delivery to target tumors while reducing undesirable systemic side effects. If the transarterial approach is combined with the highly targeted nature of radiotheranostics, then an excellent personalized therapeutic platform may evolve.
Many NETs patients have liver metastasis on presentation. As such, liver-directed therapies (LDTs), whether thermal ablation or transarterial therapies, are essential tools for managing these patients. As radiotheranostics become more available, IRs should consider whether their patients may benefit more from LDTs, radiotheranostics or both.
It seems like a simple question. However, it is a challenging one that requires familiarity with these treatment options. Until clear guidelines are available, interventional radiologists would need to use their best clinical judgment to decide, together with medical oncologists, which treatment option may be better to consider first.
In our institution, for example, we prefer to start with Lutathera for NETs if patients have significant extrahepatic disease, especially if symptomatic. For patients with liver-dominant disease, we find it reasonable to start with LDTs and leave Lutathera for a later disease stage when there is disease progression. Different institutions may follow different protocols and each case must be discussed in a tumor board to achieve consensus. It's worth noting that patients with tumoral radiotracer uptake lower than that of the background liver (Krenning score 1–2) are unlikely to benefit from Lutathera treatment while tumors with higher uptake (Krenning score 3–4) are more likely to respond to treatment given higher receptor expression.
Clinical trials are ongoing to investigate intra-arterial radiotheranostics therapies for metastatic NETs to the liver and for metastatic prostate cancer. If these trials demonstrate survival benefit of the intra-arterial approach over intravenous approach in select clinical scenarios, then interventional radiology will be expected to play a critical role in advancing the field in the near future. Currently, radiotheranostics are being administrated in most centers by authorized nuclear medicine physicians, but interventional radiologists highly interested in this field may need to get dedicated nuclear medicine training to be able to administer these radiotheranostics on a wider scale.
Where to find out more
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) has a dedicated Radiopharmaceutical Therapy Central resource (therapy.snmmi.org/snmmi-therapy) that provides valuable information for physicians interested in the clinical and research applications of radiotheranostics.
