Theranostics in nuclear medicine practice

Figures & data

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.

Table 1 Overview of theranostic agents

Theranostic molecule	Iodine	mIBG	SSA	PSMA-ligands	Benzamide/arylcarboxamide
Target	Thyroid cancer cells	Neurosecretory granules	SSTR, especially the subtype SSTR2	PSMA	Melanin
Planar imaging/SPECT or PET	^131I and ^123I	[^131I]I-mIBG, [^123I]I-mIBG	SSA labeled with indium-111	[^123I]I-MIP-1072	[^123I]I-BA52
	^124I	[^124I]I-mIBG	[^68Ga]Ga-DOTA-TATE	[^68Ga]Ga-PSMA-11	[^18F]F-ICF15002
			[^68Ga]Ga-DOTA-TOC	[^68Ga]Ga-PSMA-617
			[^68Ga]Ga-DOTA-NOC
Therapeutic agent	^131I	[^131I]I-mIBG	[^177Lu]Lu-DOTA-TATE	[^177Lu]Lu-J591	[^131I]I-BA52
			[^177Lu]Lu-DOTA-TOC	[^90Y]Y-J591	[^131I]I-ICF15002
			[^90Y]Y-DOTA-TOC	[^131I]I-MIP-1095
			[^90Y]Y-DOTA-TATE	[^177Lu]Lu-PSMA-617
Indication	Thyroid cancer	Neuroblastomas, pheochromocytomas, paragangliomas, medullary thyroid carcinomas, and other NEN	NEN, especially GEP-NEN	Metastatic prostate cancer	Metastatic melanoma

Abbreviations: mIBG, metaiodobenzylguanidine; SSA, somatostatin analogs; SSTR, somatostatin receptors; NEN, neuroendocrine neoplasia; GEP, gastroenteropancreatic system; SPECT, single photon emission computed tomography; PET, positron emission tomography.

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.