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Technetium Tc 99m Arcitumomab (Systemic)


VA CLASSIFICATION
Primary: DX201


Note: For a listing of brand names for the articles in this monograph, refer to the General Index.

Commonly used brand name(s): CEA-Scan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Diagnostic aid, radioactive (colorectal disease)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Carcinoma, colorectal (diagnosis adjunct)—Technetium Tc 99m arcitumomab, in conjunction with standard diagnostic modalities (e.g., computed tomography [CT]), is indicated to detect, locate, and determine the extent of recurrent and/or metastatic colorectal carcinoma involving the liver and the extrahepatic abdominal and pelvic regions in patients with a histologically confirmed diagnosis of colorectal carcinoma {01} {03} {04} {05} {06} {07} {08} {10} {11} {13}. Imaging with technetium Tc 99m arcitumomab provides additional information in patients suspected of tumor recurrence or metastasis who have elevated or rising serum carcinoembryonic antigen (CEA) but no evidence of disease by standard diagnostic methods (e.g., abdominal and pelvic CT, chest radiograph, colonoscopy, barium enema) {01} {07} {08} {12} {18}.

Acceptance not established
Technetium Tc 99m arcitumomab may have a role as an adjunct to mammography in the diagnosis of primary, recurrent, or metastatic mammary cancer {14} {15} {16} {17}, particularly in patients without palpable abnormalities who have indeterminate mammograms {15}. However, at present, there are insufficient data to confirm the usefulness of technetium Tc 99m arcitumomab for this indication {18}.


Physical Properties


Radionuclide
(half-life) 
Mode of
decay 
Principal
photon
emissions
(keV) 
Mean number
of emissions/
disintegration 
Tc 99m
(6 hr) 
Isomeric transition to Tc 99  Gamma
(18)
Gamma
(140.5) 
0.062
0.891 


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Arcitumomab, the Fab" fragment, is derived from purified IMMU-4 by enzymatic digestion with pepsin, which produces F(ab")2 fragments, and by subsequent reduction, the Fab" fragments {01} {08} {12}.
Molecular weight—
    Arcitumomab: approximately 50,000 daltons {01} {08}

Mechanism of action/Effect:

Arcitumomab, a Fab" fragment of the murine monoclonal antibody IMMU-4 of the IgG1 subclass, is directed against a 200,000-dalton carcinoembryonic antigen (CEA) that is expressed on the cell surface of numerous tumors, particularly of the gastrointestinal tract (including fetal gastrointestinal tissues) and in certain inflammatory states (e.g., Crohn"s disease) {01} {08} {13} {18}. The Fab" fragment is used rather than the whole monoclonal antibody because of its more favorable pharmacokinetics (faster blood clearance and minimal liver metabolism) {18} also, it minimizes the frequency of human anti-mouse antibody response {07} {09} {11} {18}. Less than 50% antigen complexation with technetium Tc 99m arcitumomab occurs with plasma CEA levels of up to 2000 nanograms per mL, and antigen complexation is not detectable at serum CEA levels below 250 nanograms per mL {01} {18}. The distribution of radioactivity is recorded by planar scintigraphy and single photon emission computed tomography (SPECT) {01} {06} {11} {12}.

Distribution:

After intravenous administration of technetium Tc 99m arcitumomab, there is moderately rapid clearance from the circulation {01} {12} {18}. Blood levels at 1, 5, and 24 hours after technetium Tc 99m arcitumomab injection have been reported as 63%, 23%, and 7% of the administered activity, respectively {01}. Technetium Tc 99m arcitumomab localizes at sites of increased CEA expression, particularly primary and/or metastatic colorectal lesions {01} {05} {08} {12} {18}. Also, accumulation of radioactivity, leading to potential false-positive readings especially with planar imaging, may occur in nontumor areas, such as in major blood pool organs (e.g., heart, major vessels), near the sites of antibody fragment excretion (e.g., kidneys and urinary bladder, and in the gallbladder and intestines) {01} {08} {12} {18}.

Half-life:


Elimination:

Initial: Approximately 1 hour {01}.

Terminal: 13 ± 4 hours {01}.


Time to radioactivity visualization:

For optimal target tissue visualization—Planar scintigraphy and SPECT are generally performed 2 to 5 hours after technetium Tc 99m arcitumomab administration {01} {03} {06} {07} {08} {11}. Selected additional views may be obtained for up to 24 hours after administration {01}.

Note: If late imaging is performed (up to 24 hours postinjection), intestinal and gallbladder activity may interfere with true tumor imaging {01}. Late images should be compared to earlier ones (2 to 5 hours) and interpreted cautiously {01}.


Radiation dosimetry:


Estimated absorbed radiation dose * 
Organ  mGy/MBq
(mean) 
rad/mCi 
Kidney  0.1   0.4 
Bladder  0.02  0.06 
Spleen  0.02  0.06 
Liver   0.01  0.04 
Red marrow  0.01  0.04 
Ovaries  0.008  0.03 
Lungs  0.008  0.03 
Testes  0.005  0.02 
Total body  0.005  0.02 
Effective dose: 0.009 mSv/MBq (0.03 rem/mCi) 
*  For adults; intravenous injection {01}.

Elimination:
    Renal (primary) {08} {09}. Approximately 28% of the administered activity is excreted within the first 24 hours {01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to murine antibody–based products may be sensitive to technetium Tc 99m arcitumomab also {01}.

Carcinogenicity/ Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of technetium Tc 99m arcitumomab have not been performed {01}.

Pregnancy/Reproduction

Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. However, studies to assess transplacental transfer of technetium Tc 99m arcitumomab have not been done in humans {01}.

To avoid the possibility of fetal exposure to radiation, in those circumstances in which the patient's pregnancy status is uncertain, a pregnancy test will help to prevent inadvertent administration of this preparation during pregnancy {01}.

Studies have not been done in animals {01}.

FDA Pregnancy Category C. {01}

Breast-feeding

Although it is not known whether technetium Tc 99m arcitumomab is distributed into breast milk {01}, it is known that Tc 99m as free pertechnetate is distributed into breast milk. To avoid radiation exposure to the infant, discontinuation of nursing for a period of 24 hours is recommended after administration of technetium Tc 99m–labeled radiopharmaceuticals {18}.

Pediatrics

Studies on the relationship of age to the effects of technetium Tc 99m arcitumomab have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of technetium Tc 99m arcitumomab in children are not expected {18}.


Geriatrics


Appropriate studies on the relationship of age to the effects of technetium Tc 99m arcitumomab have not been performed in the geriatric population. However, clinical trials and studies that included older patients were conducted, and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected {08} {12} {13}.


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Immunoassays, murine antibody–based{01}    (human anti-murine antibody [HAMA] production may be induced by the administration of murine monoclonal antibodies; although the use of the Fab' fragment almost always eliminates induction of HAMAs {07} {11} {18}, HAMAs in serum may interfere with murine antibody–based immunoassays and with in vitro or in vivo diagnostic murine antibody–based agents, and may increase the risk of adverse reactions {01} {18})


Diagnostic interference
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medical problems or conditions:
Inflammatory lesions, local or {08}

Surgical areas, recent {12}
    (localization of technetium Tc 99m arcitumomab may occur at these sites {08} {12})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Sensitivity to murine antibody–based products or to the radiopharmaceutical preparation{01}


Side/Adverse Effects

Note: Allergic reactions, including anaphylaxis, can occur in patients receiving murine antibody–based products. Although serious allergic reactions have not been reported during clinical trials with technetium Tc 99m arcitumomab, the possibility must be considered and proper treatment measures should be readily available {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence rare
    
Allergic reaction, mild, transient{01}{11}{13} (itching; skin rash)
    
bursitis (pain and inflammation at the joints)
    
eosinophilia, transient
    
fever{01}{11}{13}
    
headache{01}{11}{13}
    
nausea{01}{11}{13}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Localization of radiolabeled monoclonal antibodies in tumor sites; uptake of radioactivity may be visualized by external imaging

Small amounts of radioactivity used in diagnosis; radiation received is low and considered safe

Before using this test
»   Conditions affecting use, especially:
Sensitivity to murine antibody–based products or to the radiopharmaceutical preparation

Pregnancy—Technetium Tc 99m (as free pertechnetate) crosses the placenta; risk to fetus from radiation exposure as opposed to benefit derived from study should be considered





Breast-feeding—Not known if technetium Tc 99m arcitumomab is distributed into breast milk, but Tc 99m (as free pertechnetate) is distributed into breast milk; temporary discontinuation of nursing is recommended after administration of this agent to avoid any unnecessary absorbed radiation dose to the infant

Preparation for this test
Special preparatory instructions may apply; patient should inquire in advance

Voiding prior to imaging of the pelvis to minimize bladder activity, which may interfere with image interpretation


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are licensed by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority {01}.

The patient should void prior to imaging of the pelvis to minimize bladder activity, which may interfere with image interpretation {01}.

Safety considerationsfor handling this medication
Guidelines for the receipt, storage, handling, dispensing, and disposal of radioactive materials are available from scientific, professional, state, federal, and international bodies. Handling of this radiopharmaceutical should be limited to those individuals who are appropriately qualified and authorized {02}.

For treatment of adverse effects
Epinephrine and antihistamines should be available during the administration of technetium Tc 99m arcitumomab because of the possibility of allergic reactions {01}.




TECHNETIUM Tc 99m ARCITUMOMAB INJECTION

Usual adult administered activity
Diagnosis of colorectal carcinoma
Intravenous, 1 mg of arcitumomab radiolabeled with 740 to 1110 megabecquerels (20 to 30 millicuries) of technetium Tc 99m, administered over five to twenty minutes {01} {07} {11} {13} {14}.


Usual pediatric administered activity
Minimum dosage has not been established. {18}

Usual geriatric administered activity
See Usual adult administered activity .

Strength(s) usually available
U.S.—


1.25 mg of arcitumomab and 0.29 mg of stannous chloride, per single-use vial (Rx) [CEA-Scan (potassium sodium tartrate tetrahydrate) (sodium acetate trihydrate) (sodium chloride) (glacial acetic acid) (hydrochloric acid) (sucrose)]

Canada—


1.25 mg of arcitumomab and 0.29 mg of stannous chloride, per single-use vial (Rx) [CEA-Scan (potassium sodium tartrate tetrahydrate) (sodium acetate trihydrate) (sodium chloride) (glacial acetic acid) (hydrochloric acid) (sucrose)]

Packaging and storage:
Before radiolabeling, store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer {01}. Protect from freezing {01}.

Note: After radiolabeling, the technetium Tc 99m arcitumomab injection can be kept at room temperature {01}.


Preparation of dosage form:
To radiolabel the arcitumomab, 1110 megabecquerels (30 millicuries) of a sterile, pyrogen- and oxidant-free sodium pertechnetate Tc 99m in 0.9% sodium chloride solution is used {01}. See the manufacturer's package insert for instructions.

Stability:
The package insert states that the injection can be administered 5 minutes after radiolabeling {01} {18}. Administration should occur within 4 hours after radiolabeling {01} {18}.


Caution:
Radioactive material.



Developed: 08/26/1998



References
  1. CEA-Scan package insert (Immunomedics—US), New 7/96.
  1. Radiopharmaceuticals Advisory Panel Meeting, 4/96.
  1. Swayne LC, Goldenberg DM, Diehl WL, et al. SPECT anti-CEA monoclonal antibody detection of occult colorectal carcinoma metastases. Clin Nucl Med 1991 Nov; 16(11): 849-52.
  1. Rodriguez-Bigas MA, Bakshi S, Stomper P, et al. 99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer: a prospective study. Arch Surg 1992 Nov; 127(11): 1321-4.
  1. Lechner P, Lind P, Binter G, et al. Anticarcinoembryonic antigen immunoscintigraphy with a 99mTc- Fab' fragment (IMMU-4) in primary and recurrent colorectal cancer: a prospective study. Dis Colon Rectum 1993 Oct; 36(10): 930-5.
  1. Podoloff DA, Patt YZ, Curley SA, et al. Imaging of colorectal carcinoma with technetium-99m radiolabeled Fab' fragments. Semin Nucl Med 1993 Apr; 23(2): 89-98.
  1. Moffat FL Jr, Vargas-Cuba RD, Serafini AN, et al. Radioimmunodetection of colorectal carcinoma using technetium-99m-labeled Fab' fragments of the IMMU-4 anti-carcinoembryonic antigen monoclonal antibody. Cancer 1994 Feb; 73(3 Suppl): 836-45.
  1. Patt YZ, Podoloff DA, Curley S, et al. Technetium 99m-labeled IMMU-4, a monoclonal antibody against carcinoembryonic antigen, for imaging of occult recurrent colorectal cancer in patients with rising serum carcinoembryonic antigen levels. J Clin Oncol 1994 Mar; 12(3): 489-95.
  1. Becker BT, Hannappel E, Goldenberg DM, et al. 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 Res 1995 Dec; 55(23 Suppl): 5777S-5785S.
  1. Stomper PC, D'Souza DJ, Bakshi SP, et al. Detection of pelvic recurrence of colorectal carcinoma: prospective, blinded comparison of Tc-99m-IMMU-4 monoclonal antibody scanning and CT. Radiology 1995 Dec; 197(3): 688-92.
  1. Moffat FL Jr, Pinsky CM, Hammershaimb L, et al. 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. J Clin Oncol 1996 Aug; 14(8): 2295-305.
  1. Sirisriro R, Podoloff DA, Patt YZ, et al. 99mTc-IMMU-4 imaging in recurrent colorectal cancer: efficacy and impact on surgical management. Nucl Med Commun 1996 Jul; 17(7): 568-76.
  1. Hughes K, Pinsky HK, Petrelli NK, et al. Use of carcinoembryonic antigen radioimmunodetection and computed tomography for predicting the resectability of recurrent colorectal cancer. Ann Surg 1997 Nov; 226(5): 621-31.
  1. Goldenberg DM, Wegener W. Studies of breast cancer imaging with radiolabeled antibodies to carcinoembryonic antigen. Acta Med Austriaca 1997; 24(2): 55-9.
  1. Nabi HA, Rosner K, Pannaro V, et al. Results of CEA-Scan immunoscintigraphy in 59 patients with non-palpable, mammographically abnormal breast lesions. Abstract No. 25. Presented at SNM 44th Annual Meeting in San Antonio, TX. J Nucl Med 1997 May; 38(5 Suppl): 9P.
  1. Nabi RD, Wild L, Ortman-Nabi J, et al. Diagnosis of breast carcinoma with radiolabeled monoclonal antibodies (MoAbs) to carcinoembryonic antigen (CEA) and human milk fat globulin (HMFG). Cancer Invest 1995; 13(6): 573-82.
  1. Lind P, Smola MG, Lechner P, et al. The immunoscintigraphic use of Tc-99m-labelled monoclonal anti-CEA antibodies (BW 431/26) in patients with suspected primary, recurrent and metastatic breast cancer. Int J Cancer 1991 Apr; 47(6): 865-9.
  1. Reviewers' comments per monograph revision of 3/30/98.
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