Combining therapy with diagnostics
in nuclear medicine

Theranostics – Nuclear medicine´s fountain of youth

October 09, 2018
By: Ken Herrmann and Wolfgang P. Fendler

The term “theranostics” reigns among medicine´s hottest buzz words, being almost as popular as “artificial intelligence” and “immunoncology”. According to PubMed, the term was introduced in an abstract in 2002. Today more than 3800 hits are reported for “theranostic” or “theragnostic”. In short, theranostics is defined as “diagnostic testing employed for selecting targeted therapy.”

Interestingly, Nuclear Medicine has long applied the theranostic concept by using radioactive iodine for diagnostic imaging and therapy of thyroid cancer. In 1943 Seidlin, et al. used a Geiger counter to localize sites of metastases under 131I treatment. Whereas radioactive iodine-based theranostics are established worldwide, it took more than 70 years to successfully translate a new generation of theranostics into the clinic. Similar to radioiodine treatment, Lutathera and other theranostic probes are highly efficacious, with few serious adverse events. It was only earlier this year that Lutathera, a 177Lu-labelled somatostatin receptor agonist, was approved for clinical use in patients with rare neuroendocrine tumors (NET) by the FDA and a bit earlier by the EMA. The medical and economic excitement associated with the introduction of Lutathera represents just a small glimpse of what can be expected when new theranostic pairs are made available to diagnose and treat more prevalent malignancies such as prostate, breast, lung and/or pancreatic cancer. For prostate cancer the target of interest is the prostate specific membrane antigen (PSMA). PSMA is over-expressed by the majority of prostate cancers and was also described to have prognostic value. The introduction of specific PSMA ligands conjugable with diagnostic (68Ga-, 18F-) or therapeutic (177Lu-, 90Y-, 225Ac-) radionuclides resulted in an overwhelming demand by referring physicians and patients (Figure 1) .

Recent developments have triggered a lot of industry interest in theranostics. The acquisition of Advanced Accelerator Applications by Big Pharma (Novartis) for $3.9 billion USD, the recent surge of the Endocyte Inc. stock after licensing a theranostic to be applied to prostate cancer, as well as the reimbursement level of around $47,500 USD per dose of Lutathera highlight the emerging economic relevance of theranostics and therefore nuclear medicine. However, opportunities are associated with challenges such as setting up the required infrastructure, training the healthcare professionals, establishing the appropriate position of a new therapeutic within established treatment algorithms and many more. There are approximately 40 dedicated theranostic centers in Germany supplying a population of 80 million citizens. Translating this number to a population of 320 million in the U.S. suggests a need of around 160 theranostic centers. Few early adopters, such as UCLA, UCSF and MSKCC, among others, are currently setting up dedicated theranostic centers in the U.S. Others are hesitant due to unknown regulatory (FDA approval) and reimbursement status, which renders development of solid business plans difficult. In addition, only few in the U.S. have been appropriately trained in theranostics. There is, therefore, an unmet need to train a wide spectrum of healthcare professionals, including nurses, technologists, physicists, radiation safety officers, and medical doctors. At the same time this also provides an opportunity to attract young, motivated people, including specialists from other fields, such as medical oncology, gastroenterology, endocrinology, and urology to nuclear medicine.

Supply of theranostic compounds remains another significant roadblock to widespread adoption. Some experts, using conservative models, predicted an annual need of around 30,000 doses of Lutathera for NET and around 160,000 doses of 177Lu-PSMA for prostate cancer patients. Based on 250 work days per year this results in an average of 760 doses per day and, including a safety margin, the need to produce 800-1000 doses per day. However, the current production infrastructure as well as the 177Lu-supply are far from ready to meet this demand. This crisis provides an opportunity for industry, insurances, health care providers and health care professionals to come up with mutually beneficial solutions.

As outline above, the demand for theranostics will be high. However, with the development and emergence of additional novel theranostics the demand is likely to become even higher. These new compounds will be applicable to NET and other somatostatin receptor expressing tumors (177Lu-Satoreotide), neurotensin-1 receptor ligands, possibly for pancreactic cancer among others (177Lu-3BP-227), CD37-binding antibodies for hematological malignancies (Betalutin) and the recently approved 131MIBG (Azedra) for neuroblastoma and pheochromocytoma. More recently introduced ligands targeting tumor stroma (Fibroblast Activation Protein (FAPI)) may find even wider application in various cancers.

Ken Herrmann
In summary, theranostics provides unique new opportunities and challenges for nuclear medicine and industry regulators, insurances and healthcare systems. But there is no time to hesitate – the future is now!

Wolfgang P. Fendler
About the authors: Ken Herrmann and Wolfgang P. Fendler work in the department of Nuclear Medicine, Universitätsklinikum Essen, Essen, Germany. Ken Herrmann is also associated with the Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California.