Theranostics in nuclear medicine practice

Abstract

The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.

Keywords: PET/CT; diagnostics; nuclear medicine; personalized medicine; theranostics; therapy.

Figure 1

The theranostic principle in nuclear medicine involves combining diagnostic imaging and therapy with the same molecule, which is radiolabeled differently, or administered in other dosages. In case of radioiodine therapy (RAI), the radioisotope (¹³¹I or ¹²³I) can be directly mediated by the sodium-iodide symporter in the thyroid cells. In other cases, it can be more complex. The image shows a simplified model of a radiopharmaceutical, which consists of a binding molecule that binds the target, and a linking molecule, which binds the radioisotope. Examples of such theranostic molecules are DOTA-TOC, DOTA-TATE, and PSMA-617.

Figure 2

(A) Initial ¹³¹I-planar images of a 74-year-old female with metastatic thyroid cancer (lung, bone, and intracranial soft-tissue metastases, marked with arrows). The tumor marker thyroglobulin (Tg) before radioiodine therapy (RAI) was 572 ng/mL. (B) After two administrations of RAI (cumulative activity: 14.3 GBq), the patient was in complete remission with the Tg at 0.2 ng/mL. The planar images show only a physiological uptake of the radiotracer in the gastrointestinal tract and pharyngeal mucosa (marked with an asterisk).

Figure 3

(A) [⁶⁸Ga]Ga-DOTA-TOC-image* of a male patient with a neuroendocrine tumor (unknown origin) 23 months after the baseline PRRT (three cycles, cumulative activity: 19.6 GBq). The patient had a recurrence of the disease with multiple metastases in the bone, lung, liver, and lymph nodes (marked with arrows). (B) After another course of PRRT (three cycles, cumulative: 43.4 GBq), the PET images showed a partial response. Note: *Maximum-intensity projection (MIP) PET image is a visualization technique that provides an initial overview of the case. Abbreviations: PET, positron emission tomography; PRRT, peptide receptor radionuclide therapy.

Figure 4

(A) Pre-therapeutic [⁶⁸Ga]Ga-PSMA-11 images* of a patient with multiple lymph node, peritoneal, and bone metastases (arrows), and history of chemotherapy (first and second line) with enzalutamide and abiraterone. (B) After three cycles of [¹⁷⁷Lu]Lu-PSMA-617, the follow-up images showed a very good response with a substantial PSA decline. Note: *Maximum-intensity projection (MIP) PET image is a visualization technique that provides an initial overview of the case. Abbreviations: PET, positron emission tomography; PSA, prostate-specific antigen.