Technetium (99mTc) arcitumomab explained

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.

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.^[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.

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.

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

Further reading

• Primus FJ, Newell KD, Blue A, Goldenberg DM . Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies . Cancer Research . 43 . 2 . 686–92 . February 1983 . 6184152 .
• Hansen HJ, Jones AL, Sharkey RM, Grebenau R, Blazejewski N, Kunz A, Buckley MJ, Newman ES, Ostella F, Goldenberg DM . 6 . Preclinical evaluation of an "instant" 99mTc-labeling kit for antibody imaging . Cancer Research . 50 . 3 Suppl . 794s–798s . February 1990 . 2297726 .
• Hughes K . Use of radioimmunodetection with CEAScan in planning for resection of recurrent colorectal cancer. Proc Amer Soc Clin Oncol. 14. 1995. 544.
• Moffat FL, Pinsky CM, Hammershaimb L, Petrelli NJ, Patt YZ, Whaley FS, Goldenberg DM . 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 . August 1996 . 8708720 . 10.1200/JCO.1996.14.8.2295 .

Notes and References

1. Web site: CEA-Scan Summary of Product Characteristics. Immunomedics. 2009-10-28. 2016-03-13. https://web.archive.org/web/20160313061725/http://cea-scan.com/inserts/epckginst.htm. dead.
2. Guadagni F, Kantor J, Aloe S, Carone MD, Spila A, D'Alessandro R, Abbolito MR, Cosimelli M, Graziano F, Carboni F, Carlini S, Perri P, Sciarretta F, Greiner JW, Kashmiri SV, Steinberg SM, Roselli M, Schlom J . 6 . 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 . March 2001 . 11289125 .
3. Behr T, Becker W, Hannappel E, Goldenberg DM, Wolf F . 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 . December 1995 . 7493346 .