Technetium (99mTc) arcitumomab

Technetium (99mTc) arcitumomab
Monoclonal antibody
Type Fab' fragment
Source Mouse
Target CEA
Clinical data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Intravenous
Legal status
  • (Prescription only)
Pharmacokinetic data
Bioavailability N/A
Biological half-life 13 ± 4 hours
Identifiers
CAS Number 154361-48-5 YesY (arcitumomab)
ATC code V09IA06
ChemSpider none
UNII 029JF1SCU8 YesY
Chemical data
Molar mass ca. 50 kg/mol
  (verify)

Technetium (99mTc) arcitumomab is a drug used for the diagnostic imaging of colorectal cancers, marketed by Immunomedics.[1] It consists of the Fab' fragment of a monoclonal antibody (arcitumomab, trade name CEA-Scan) and a radionuclide, technetium-99m.

Chemistry

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

Arcitumomab recognizes carcinoembryonic antigen (CEA), an antigen over-expressed in 95% of colorectal cancers.[2] 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][3]

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.[1]

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 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.

References

  1. 1 2 3 4 5 6 "CEA-Scan Summary of Product Characteristics". Immunomedics.
  2. Guadagni, Fiorella; Kantor, J; Aloe, S; Carone, MD; Spila, A; D'alessandro, R; Abbolito, MR; Cosimelli, M; et al. (15 March 2001). "Detection of Blood-borne Cells in Colorectal Cancer Patients by Nested Reverse Transcription-Polymerase Chain Reaction for Carcinoembryonic Antigen Messenger RNA". Cancer Research 61 (6): 2523–32. PMID 11289125.
  3. Behr, T; Becker, W; Hannappel, E; Goldenberg, DM; Wolf, F (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.

Further reading

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