Technetium (99mTc) arcitumomab
| Monoclonal antibody | |
|---|---|
| Type | Fab' fragment |
| Source | Mouse |
| Target | CEA |
| Clinical data | |
| Routes of administration | Intravenous |
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| Pharmacokinetic data | |
| Bioavailability | N/A |
| Elimination half-life | 13 ± 4 hours |
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| Chemical and physical data | |
| Molar mass | 54 kDa[citation needed] |
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Technetium (99mTc) arcitumomab was a drug used for the diagnostic imaging of colorectal cancers, marketed by Immunomedics.[1] It consisted of the Fab' fragment of a monoclonal antibody (arcitumomab, trade name CEA-Scan) and a radionuclide, technetium-99m.
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. [2]
Chemistry
[edit]Technetium (99mTc) arcitumomab is an immunoconjugate. Arcitumomab is a Fab' fragment of IMMU-4, a murine IgG1 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.[1]
Mechanism of action
[edit]Arcitumomab recognizes carcinoembryonic antigen (CEA), an antigen over-expressed in 95% of colorectal cancers.[3] 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 or progression, and metastases of the tumour can be obtained.[1][4]
Contraindications
[edit]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.[1]
Adverse effects and overdose
[edit]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 grand mal after application.[1]
Radioactivity can lead to radiation poisoning. Since the dose of an arcitumomab application is about 10 mSv,[1] such an overdose is unlikely.
Removal from market
[edit]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.[5]
References
[edit]- ^ a b c d e f "CEA-Scan Summary of Product Characteristics". Immunomedics. Archived from the original on 2016-03-13. Retrieved 2009-10-28.
- ^ "CEA-Scan | European Medicines Agency (EMA)". www.ema.europa.eu. 2005-11-16. Retrieved 2024-09-30.
- ^ Guadagni F, Kantor J, Aloe S, Carone MD, Spila A, D'Alessandro R, et al. (March 2001). "Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers". Cancer Research. 61 (6): 2523–32. PMID 11289125.
- ^ Behr T, Becker W, Hannappel E, Goldenberg DM, Wolf F (December 1995). "Targeting of liver metastases of colorectal cancer with IgG, F(ab')2, and Fab' anti-carcinoembryonic antigen antibodies labeled with 99mTc: the role of metabolism and kinetics". Cancer Research. 55 (23 Suppl): 5777s–5785s. PMID 7493346.
- ^ "CEA-Scan | European Medicines Agency (EMA)". www.ema.europa.eu. 2005-11-16. Retrieved 2024-09-30.
Further reading
[edit]- Primus FJ, Newell KD, Blue A, Goldenberg DM (February 1983). "Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies". Cancer Research. 43 (2): 686–92. PMID 6184152.
- Hansen HJ, Jones AL, Sharkey RM, Grebenau R, Blazejewski N, Kunz A, et al. (February 1990). "Preclinical evaluation of an "instant" 99mTc-labeling kit for antibody imaging". Cancer Research. 50 (3 Suppl): 794s–798s. PMID 2297726.
- Hughes K (1995). "Use of radioimmunodetection with CEAScan in planning for resection of recurrent colorectal cancer". Proc Amer Soc Clin Oncol. 14: 544.
- Moffat FL, Pinsky CM, Hammershaimb L, Petrelli NJ, Patt YZ, Whaley FS, Goldenberg DM (August 1996). "Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group". Journal of Clinical Oncology. 14 (8): 2295–305. doi:10.1200/JCO.1996.14.8.2295. PMID 8708720.