Interventional radiology (IR) is a main player in modern clinical oncology practice. Almost every tumour board has a seat for IR. Clinical oncology is a rapidly evolving field as well; new therapies are being introduced frequently allowing for treatment of a wide spectrum of cancers. Among these treatment options, radiotheranostics represent a unique platform where diagnostic and therapeutic purposes are combined into a single paradigm. This allows diagnosis and treatment of advanced stages of cancer with high precision, fitting very well into the modern concept of personalised medicine.
Peptide receptor radionuclide therapy (PRRT) is the most common radiotheranostic form in clinical practice. The two most widely available radiopharmaceuticals currently are Lutathera for treatment of gastroenteropancreatic neuroendocrine tumours (GEP- NETs) and Pluvicto for treatment of castration resistant metastatic prostate cancer. Different clinical specialties, including nuclear medicine, IR, medical and radiation oncology have high interest in radiotheranostics. With many specialties digging into this field, it is extremely important for the interventional radiologists to be updated about the advances in radiotheranostics. The aim of this article is to update IRs about the key concepts of radiotheranostics and to explore ways by which IR remains a key player in modern oncology practice.
To start with, most interventional radiologists are familiar with the use of yttrium-90 (Y90), loaded on resin or glass microspheres, for transarterial treatment of liver tumours. However, there are significant differences between Y90 therapy and PRRT. Resin or glass loaded Y90 microspheres are essentially flow directed therapists; blood flow dynamics are the main factors controlling microspheres distribution. PRRT have the additional advantage of being linked to receptor specific ligands. This allows these radiopharmaceuticals to attach to active, disease specific, receptors which can be easily screened for and quantified using advanced PET/CT imaging tracers. Additionally, there are key differences between Lutetium-177 (177Lu) (a common radionuclide for clinical PRRT radiopharmaceuticals) and Y90. While both are beta particle emitters, Y90 is known to have a longer penetration range (maximum=11mm, mean=3.9mm) and higher energy (mean of 0.94MeV) compared to 177Lu which has a mean energy of 0.15MeV and shorter penetration range in human tissues (maximum=1.7mm, mean=0.23mm). These differences may have implications on patients selection for either therapies, as detailed later herein.
Interventional radiologists need to be aware of the fact that, as more clinical theranostic therapies become available, the decision-making process regarding the best treatment option in specific clinical scenarios will become more sophisticated. For example, many metastatic NETs present with liver metastatic disease. These patients have historically been treated by liver directed therapies (LDTs) and thermal ablation. With Lutathera now on board, questions may arise about whether metastatic liver disease would respond better to LDTs versus PRRT. The answer to this question is onerous and requires expertise in the field, sometimes even extended discussions in multidisciplinary tumour boards. A higher somatostatin receptor expression, reflected by a higher Krenning score of 3 or 4, is a good predictor of favourable response to PRRT. On the other hand, lower Krenning score metastatic deposits reflect lower receptor expression and may respond better to LDTs. Another factor to consider is the extent of metastatic disease. In our experience, patients with extrahepatic widespread metastatic disease are good candidates for intravenous PRRT therapy, while liver only/dominant metastatic disease may be better candidates for early LDTs, preserving PRRT for later advanced stages. The higher penetration range and beta particle energy of Y-90 spheres may favor the use of Y-90 intra-arterial therapy for large infiltrative tumours and may explain that tumours >2–3cm in size may not respond well to PRRT.
An exciting potential opportunity for interventional radiologists is the possible intra-arterial administration of PRRT, combining the high selective advantage of catheter-directed therapy with precise receptor-targeting potential of PRRT. Several studies have demonstrated a higher tumour to background uptake using the intra-arterial approach. However, more studies are needed to investigate how this may reflect on progression-free and overall survival. If proved to add survival benefit, intra-arterial PRRT can be a unique niche for those interested in this field.
To conclude, theranostics therapy is a rapidly evolving field with lots of potential in modern oncology practice. Interventional radiologists, who are already key players in interventional oncology practice, need to realise the added value of this innovative paradigm and make necessary changes to their practice in response to the advances in the field. Radiotheranostics should not be visualised as a source of threat for IR practice, but rather a gateway to one of the most revolutionary treatments of cancer in the coming years.
Islam Elhelf is a clinical assistant professor and programme director at Augusta University (Augusta, USA).