Technetium (^99mTc) arcitumomab is 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 or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

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. Goldenbe ...

. It consists of the

Fab' fragment The fragment antigen-binding region (Fab region) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the a ...

of a monoclonal antibody (arcitumomab, trade name CEA-Scan) and a

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 ...

, technetium-99m.

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 murine

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 a ...

monoclonal antibody extracted from the ascites of mice. The enzyme pepsin 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 (^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 transp ...

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 ...

(CEA), an antigen over- expressed in 95% of colorectal cancers. Consequently, the antibody accumulates in such tumours together with the radioisotope, which emits photons. Via single photon emission computed tomography (SPECT), high-resolution images showing localisation,

remission Remission often refers to: *Forgiveness Remission may also refer to: Healthcare and science *Remission (medicine), the state of absence of disease activity in patients with a chronic illness, with the possibility of return of disease activity *R ...

or progression, and metastases of the tumour can be obtained.

Contraindications

Technetium (^99mTc) arcitumomab is contraindicated 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 x 109/ L (i.e. 1,500/μL). The hypereosinophilic syndro ...

, itching and fever. Some patients develop human anti-mouse antibodies, so there is the theoretical possibility of

anaphylactic reactions Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

. 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 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