Role of theranostics in thoracic oncology

Abstract

Theranostics is a re-emerging field of medicine that aims to create targeted agents that can be used for diagnostic and/or therapeutic indications. In the past, theranostics has been used to treat neoplasms, such as thyroid cancer and neuroblastomas. More recently, theranostics has seen a resurgence with advent of new therapeutic antibodies and small molecules which can be transformed into Theranostic agents through radioconjugating with a radioactive isotope. Positron emitting radioisotopes can be used for diagnostic purposes while alpha- and beta-emitting radioisotopes can be used for therapy. The technique of radiolabeling an existing therapeutic agent (small molecule or antibody) leverages the existing qualities of that drug, and potentiates therapeutic effect by conjugating it with a cytotoxic-energy bearing radioisotope (e.g., 131-iodine, 177-lutetium). Theranostics have been used for a few decades now, starting with 131-iodine for therapy of autoimmune thyroiditis (Graves' disease, Hashimoto's thyroiditis) as well as for thyroid cancer. Additionally, 131-iodine-meta-iodobenzylguanidine (131-I-MIBG) initially had been used for gastroenteropancreatic neuroendocrine (carcinoid) tumors. However, recently clinical trials have start enrolling patients to evaluate efficacy of 131-I-MIBG in patients with small cell carcinoma of the lung. In the era of precision medicine and personalized targeted therapeutics, Theranostics can play a key pivotal in improving diagnostic and therapeutic specificity by increasing potency of these targeted small molecules and antibodies with radioisotopes. In this review, we will review various clinically relevant Theranostics agent and their utility in thoracic disorders, notably within oncology.

Keywords: AXL; CAR T; FDG; FET; FLT; PSMA; Theranostics; lung metastasis; lymphoma; mIBG; neuroendocrine tumors; non-small cell lung cancer (NSCLC); nuclear medicine; positron emission tomography (PET); small cell lung cancer (SCLC); thoracic adenopathy; thymoma.

Figure 1

(A,B) FDG vs. Gallium-PSMA, respectively. A 53-year-old male with metastatic prostate cancer, with history of increasing PSA. FDG PET shows nonspecific low level metabolic activity in the skeletal system. However, Gallium-PSMA, shows focal nodular FDG uptake in multiple osseous structures including right clavicle, multiple thoracic vertebrae (T2 shown) vertebral body, right scapular and right humerus. Additionally, bilateral rib lesions are seen on the gallium PSMA PET and were occult on the FDG PET scan. (C,D) FDG vs. Gallium-PSMA, respectively. A 65-year-old male with elevated PSA and LDH presents with rib pain and shortness of breath. FDG-PET CT shows sclerosis in the sternum, ribs bilaterally and bilateral humeri, without significant FDG uptake. Gallium-PSMA shows marked radiotracer uptake in the aforementioned sclerotic lesions, consistent with widespread osseous metastases. Additionally, gallium-PSMA PET shows a metastatic right hilar lymph node which was occult on the FDG PET scan. Images generated through COH Trial NCT04216134.