Technetium (^99mTc) arcitumomab was a drug used for the diagnostic imaging of

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

s, 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. Goldenb ...

. It consisted 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 antibodie ...

(arcitumomab, trade name CEA-Scan) and a

radionuclide A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ...

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 Radiophar ...

. CEA-Scan was approved by the European Medicine Association (EMA) on October of 1996 for imaging in the case of metastases and/or recurrence in patients that were suffering from colon or rectum cancer. Under the same decision, it was also approved to be used in patients that were suspected to have colon or rectal carcinoma recurrence and/or metastasis in association with rising blood CEA-levels.

Chemistry

Technetium (^99mTc) arcitumomab is an immunoconjugate. Arcitumomab is a Fab' fragment of IMMU-4, a

murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...

IgG1 Immunoglobulin G (IgG) 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 ant ...

monoclonal antibody extracted from the

ascites Ascites (; , meaning "bag" or "sac") 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 abdo ...

of mice. The enzyme

pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...

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 Technetium-99m, 99mTc isotope ( ...

(^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 trans ...

Mechanism of action

Arcitumomab recognizes

carcinoembryonic antigen Carcinoembryonic antigen (CEA) describes a set of highly-related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is us ...

(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 particles that can ...

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 spreading 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, ...

of the tumour can be obtained.

Contraindications

Technetium (^99mTc) arcitumomab is

contraindicated In medicine, a contraindication is a condition (a situation or factor) 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 rea ...

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 Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 billion/ L (1,500/ μL). The hypereosinophilic syndrome ...

, 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

grand mal Grand may refer to: People with the name * Grand (surname) * Grand L. Bush (born 1955), American actor Places * Grand, Oklahoma, USA * Grand, Vosges, village and commune in France with Gallo-Roman amphitheatre * Grand County (disambiguation), s ...

after application. Radioactivity can lead to

radiation poisoning Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. Symptoms can start wit ...

. Since the dose of an arcitumomab application is about 10 m Sv, such an overdose is unlikely.

Removal from market

In August 2005, the marketing company Immunodemics voluntarily decided to withdraw the product from the market. In September 2005, EMA accepted the decision and CEA-Scan was removed from the market.

Chemistry

Mechanism of action

Contraindications

Adverse effects and overdose

Removal from market

References

Further reading