Theranostics- What is the Concept

There is a significant growth in number of therapeutic applications of radiopharmaceuticals. This opens new avenues of clinical interest to the Nuclear Medicine specialty.

Theranostics is its most important concept. It combines diagnostic and therapeutic capabilities with radiopharmaceuticals derived from binding to a specific molecular target. Theranostic applications use the same molecule labelled with a γ or positron emitter radionuclide for diagnosis and a β minus or α emitter radioisotope for therapy.

For almost 80 years, the best-known theranostic paradigm is represented by radioactive iodine, namely the pair Iodine-123 (γ emitter) – Iodine-131 (β minus emitter) for thyroid disease diagnosis and therapy, respectively. The first Iodine-131 treatments for hyperthyroidism were in 194187 and 1946 for thyroid cancer.

Another example is metaiodobenzylguanidine (MIBG) labeled with Iodine-123 or Iodine-131 for advanced pheochromocytoma and neuroblastoma diagnosis and treatment, respectively. Bone imaging and palliation with radiolabeled bisphosphonates (e.g.99mTc-HDP and 188Re-HEDP) is another longstanding example.

Recently, several studies demonstrated the efficacy of systemic therapy with peptide receptor radionuclide therapy in patients with advanced metastatic neuroendocrine neoplasms, using somatostatin-analogs (e.g. DOTA-TATE and DOTA-TOC) labeled with either Yttrium-90 or Lutetium-177.

The first randomized controlled Phase III study, NETTER-1 showed a significant clinical benefit from this therapy, achieving a prolonged progression-free survival of around 40 months, an overall response rate of 18% and presumably, a longer overall survival (median not reached) than standard treatment. This treatment, 177Lu-DOTA-TATE (Lutathera®), was approved by EMA in 2017 and FDA in 2018.

During the last 5 years, several studies have demonstrated treatment efficacy of 177Lu-PSMA ligands, reaching biochemical response in more than 50% of the patients. Partial response, measured by imaging, was achieved in more than one-third of the total number of patients. 

Despite the utility of β-minus emitters (Yttrium-90 and Lutetium-177), α-emitters (Actinium-225 and Astatine-211) have the major advantage of lower penetration power, resulting in a more potent absorbed dose to the tumoral lesions.

Good overall treatment response and reduced adverse effects have led to increasing research and development in this field and new therapeutic agents will soon be available.