Technetium (^99mTc) arcitumomab is a drug used for the diagnostic imaging of colorectal cancers, marketed by

Immunomedics Immunomedics was a biotechnology company focused on the development of antibody-drug conjugates for the treatment of cancer. In 2020, the company was acquired by Gilead Sciences. History Immunomedics was founded in July 1982 by David M. Goldenbe ...

. It consists of the Fab' fragment of a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

(arcitumomab, trade name CEA-Scan) and a radionuclide,

technetium-99m Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical ra ...

Chemistry

Technetium (^99mTc) arcitumomab is an

immunoconjugate Immunoconjugates are antibodies conjugated (joined) to a second molecule, usually a toxin, radioisotope or label. These conjugates are used in immunotherapy and to develop monoclonal antibody therapy as a targeted form of chemotherapy when they ar ...

. Arcitumomab is a Fab' fragment of IMMU-4, a

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IgG1 Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

monoclonal antibody extracted from the

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

of mice. The enzyme

pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides. It is produced in the gastric chief cells of the stomach lining and is one of the main digestive enzymes in the digestive systems of humans and many other animals, w ...

cleaves the F(ab')₂ fragment off the antibody. From this, the Fab' fragment is prepared by mild reduction. Before application, arcitumomab is reconstituted with a solution of the radioactive agent sodium

pertechnetate The pertechnetate ion () is an oxyanion with the chemical formula . It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope (half-life 6 hou ...

(^99mTc) from a

technetium generator A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a decaying sample of molybdenum-99. 99Mo has a half-life of 66 hours and can be easily transpo ...

Mechanism of action

Arcitumomab recognizes carcinoembryonic antigen (CEA), an antigen over- expressed in 95% of colorectal cancers. Consequently, the antibody accumulates in such tumours together with the radioisotope, which emits

photon A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they a ...

s. Via

single photon emission computed tomography Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...

(SPECT), high-resolution images showing localisation, remission or progression, and

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

of the tumour can be obtained.

Contraindications

Technetium (^99mTc) arcitumomab is

contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

for patients with known allergies or hypersensitivity to mouse proteins, as well as during pregnancy. Women should pause breast feeding for 24 hours after application of the drug.

Adverse effects and overdose

Only mild and transient side effects have been observed, mostly immunological reactions like eosinophilia, itching and fever. Some patients develop human anti-mouse antibodies, so there is the theoretical possibility of anaphylactic reactions. High doses of IMMU-4 (up to 20-fold diagnostic arcitumomab dose) have not led to any serious events. One patient has been reported to develop a

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after application. Radioactivity can lead to radiation poisoning. Since the dose of an arcitumomab application is about 10 m Sv, such an overdose is unlikely.

Chemistry

Mechanism of action

Contraindications

Adverse effects and overdose

References

Further reading