From the Magic Bullet to Theragnostics: Certitudes and Hypotheses, Trying to Optimize the Somatostatin Model

SIMPLE SUMMARY: In oncology, the hypothetical “perfect magic bullet” should have a specific target on tumor cells which allows one to target only the tumor, in the absence of uptake in normal and/or non-neoplastic cells. Theragnostics is a strategy that strictly combines diagnosis and therapy, which creates the conditions for an “a priori” definition of an effective therapeutic effect. The most complete theragnostic and “magic bullet” experiences in clinical practice are those associated with radioiodine and somatostatin model. In this paper, we analyze whether it could be possible to improve present clinical results, further extending the survival of a wider number of patients, expanding the recruitment criteria to other types of pathology, and improving the quality of life. The ultimate goal is to transform the theragnostic strategy based on the somatostatin model into a curative therapy in the highest possible number of patients. ABSTRACT: The first “theragnostic model”, that of radioiodine, was first applied both in diagnosis and therapy in the 1940s. Since then, many other theragnostic models have been introduced into clinical practice. To bring about the closest pharmacokinetic connection, the radiocompound used for diagnosis and therapy should be the same, although at present this is rarely applicable. Today, a widely applied and effective model is also the “DOTA-Ga-68/Lu-177”, used with success in neuroendocrine tumors (NET). In this paper, we analyze the necessary steps from the in vitro evaluation of a target to the choice of radionuclide and chelate for therapy up to in vivo transition and clinical application of most employed radiocompounds used for theragnostic purposes. Possible future applications and strategies of theragnostic models are also highlighted.