DOTA-TATE (DOTATATE, DOTA-octreotate, oxodotreotide, DOTA-(Tyr³)-octreotate, and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator. DOTA-TATE can be reacted with the

radionuclide A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transfer ...

s gallium-68 (T_1/2 = 68 min), lutetium-177 (T_1/2 = 6.65 d) and copper-64 (T_1/2 = 12.7 h) to form radiopharmaceuticals for

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...

(PET) imaging or radionuclide therapy. ¹⁷⁷Lu DOTA-TATE therapy is a form of

peptide receptor radionuclide therapy Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs). Mechanism A key advantage of ...

(PRRT) which targets somatostatin receptors (SSR). In that form of application it is a form of targeted drug delivery.

Chemistry and mechanism of action

DOTA-TATE is a compound containing tyrosine³-octreotate, an SSR agonist, and the bifunctional chelator DOTA (tetraxetan). SSRs are found with high density in numerous malignancies, including CNS, breast,

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

, and lymphatics. The role of SSR agonists (i.e. somatostatin and its analogs such as octreotide, somatuline and vapreotide) in neuroendocrine tumours (NETs) is well established, and massive SSR overexpression is present in several NETs. ( Tyr³)-octreotate binds the transmembrane receptors of NETs with highest activity for SSR2 and is actively transported into the cell via

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

, allowing trapping of the radioactivity and increasing the probability of the desired double-strand DNA breakage (for tumour control). Trapping improves the probability of this kind of effect due to the relatively short range of the beta particles emitted by ¹⁷⁷Lu, which have a maximum range in tissue of <2 mm. Bystander effects include cellular damage by free radical formation.

Clinical applications

Gallium-68 DOTA-TATE

⁶⁸Ga DOTA-TATE (gallium-68 dotatate, GaTate) is used to measure tumor SSR density and wholebody bio-distribution via PET imaging. ⁶⁸Ga DOTA-TATE imagery has a much higher

sensitivity Sensitivity may refer to: Science and technology Natural sciences * Sensitivity (physiology), the ability of an organism or organ to respond to external stimuli ** Sensory processing sensitivity in humans * Sensitivity and specificity, statisti ...

and resolution compared to ¹¹¹In octreotide gamma camera or SPECT scans, due to intrinsic modality differences.

Copper-64 DOTA-TATE

Copper (⁶⁴Cu) oxodotreotide or copper Cu 64 dotatate, sold under the brand name Detectnet, is a radioactive diagnostic agent indicated for use with

(PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults. It was FDA approved in September 2020. These are the same indications for as the gallium DOTA-TATE scans, but Cu-64 has advantages over Ga-68 in having a 12-hour half life rather than the much shorter one-hour half life of Ga-68, making it easier to transport from central production locations.

Lutetium-177 DOTA-TATE

The combination of the beta emitter ¹⁷⁷Lu with DOTA-TATE can be used in the treatment of cancers expressing the relevant somatostatin receptors. The U.S. Food and Drug Administration (FDA) considers ¹⁷⁷Lu-dotatate to be a first-in-class medication. Alternatives to ¹⁷⁷Lu-DOTA-TATE include ⁹⁰Y (T_1/2 = 64.6 h) DOTA-TATE. The longer penetration range in the target tissues of the more energetic

beta particle A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus during the process of beta decay. There are two forms of beta decay, β� ...

s emitted by ⁹⁰Y (high average beta energy of 0.9336 MeV) could make it more suitable for large tumors while ¹⁷⁷Lu would be preferred for smaller volume tumors.

References