Head of Nuclear Medicine Physics, Guy’s & St. Thomas’ NHS Foundation Trust
Nuclear medicine diagnostics and molecular radiotherapy (mRT) has always been ahead of the curve. Theranostics, multidisciplinary teams and just-in-time medicine are its business well before these became the future of healthcare.
For over sixty years, nuclear medicine has used tracer amounts of radioactive radioiodine to diagnose thyroid cancer. Areas of disease are highlighted by diagnostic imaging, meaning they can be successfully treated with larger doses of the same radionuclide.
Early-day theranostics, diagnostics and therapy link together to provide upfront assurance that a therapeutic option will target disease. In the case of mRT (or targeted radionuclide therapy), theranostics can optimise the radiation dose to provide a treatment effect with minimum side effects to the patient.
Used to treat thyroid cancer, radioiodine is the bedrock of mRT, but it is challenging. It has its place as a useful therapy as it is a curative option.
Treatments with radioactive iodine 131 traditionally require an inpatient stay in rooms with lead shielding. Due to the high-energy gamma emissions, lengthy, complex, post-therapy radiation protection advice is crucial after patients are discharged.
This downside has not gone unrecognised and has led to research trials for the introduction of smaller, administered activities in low-risk disease that can be provided as a day case. This has been a great step forward for the management of thyroid cancer and an indication that inpatient stays and long radiation protections restrictions for patients are barriers for acceptance of mRT by patients and healthcare systems.
Treatments using radioactive medical products have always hidden in the shadows due to complex regulatory requirements and specialist facilities. The subtle differences in the physical characteristics of the radiopharmacology are crucial in determining the acceptance of a new procedure.
Two newcomers, 223Radium-DiChloride (223RaCl, Xofigo) and the peptide receptor, radionuclide therapy (PRRT) 177Lutetium Dotatate (Lutathera), have advantages beyond the evidence of excellent clinical outcomes for the patient.
Treatments using radioactive medical products have always hidden in the shadows due to complex regulatory requirements and specialist facilities.
177Lutetium is an isotope with the required beta emissions profile for treatment with the added benefit of a gamma emission. This delivers enough to provide excellent-quality imaging while using standard nuclear medicine equipment but without lengthy gamma emissions, which would require additional radiation protection advice post-discharge.
Highly detailed, post-therapy imaging provides clinicians and patients with understanding of the disease status and comparison with pre-therapy theranostics for patients with suspected neuroendocrine tumours (NET) provided by the somatostatin receptor, PET tracer 68Gallium-Dotatate.
Greater impact on staff preparing and administering treatments
In comparison, 90Yttrium – a pure beta emitter – has the potential for excellent mRT therapy and can be labeled to peptides for PPRT. Unlike 177Lutetium, the beta emissions from 90Yttrium are considerably higher energy and cause more issues for staff preparing and administered treatments. Additionally, there is the added blow that post-therapy imaging using 90Yttrium, although possible, is not good quality and therefore does not facilitate comparisons between cycles of treatment and with detailed images provided by diagnostic PET imaging.
Perhaps for these reasons 177Lutetium-Dotatate, with its superior imaging characteristics, attracted initial interest and funding for patient trials, which led to its acceptance as a treatment option for patients with NET.
The low-toxicity of 223Ra makes it a versatile treatment option
223Ra-Cl provides palliative treatment of bone pain in men with prostate cancer and is approved by NICE. Translation of this innovative product, the first clinical use of alpha emitters, was made easier by the physical properties of 223Ra. One per cent of its decay is a gamma emission that conveniently allows the radioactivity to be measured accurately using conventional equipment. Without this, its adoption would be more problematic, slower and costly.
So, in a population that needs treatments with low toxicity, it’s a benefit that it can be administered via a quick injection once a month for six months on an outpatient basis. The treatment requires no complicated radiation protection guidance thanks to the properties of alphas; patients can have it and just go home.
The importance of discussing post-treatment advice to patients
Nuclear medicine does not function without the whole team: the patient, nuclear medicine physicians, radiologists, imaging technologists, nurses and nuclear medicine physicists. mRT has always required the patient to be consulted.
Post-treatment advice to family and friends on reducing radiation doses requires two-way conversations on the practicalities of life. There must be compromise and understanding on both sides to ensure the best outcomes.
Nuclear medicine theranostics is the ultimate just-in-time medicine. It comprises short-lived radiopharmaceuticals, optimised to deliver high radiation doses to tumours. It benefits from a fast rate of decay, so reduces side effects to other organs. This therapy allows patients to return home with minimal disruption to their lives.
Future innovations in mRT need to consider the benefits beyond clinical trials to ensure acceptance in healthcare systems that need simplicity to ensure long-term sustainability.