Professional Drug Information > Indium In 111 Satumomab Pendetide

Indium In 111 Satumomab Pendetide (Systemic)

VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): OncoScint CR/OV.

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

^†Not commercially available in Canada.

Category:


Diagnostic aid, radioactive (extrahepatic malignant disease)—

Indications

Accepted

Extrahepatic malignant disease (diagnosis)—Indium In 111 satumomab pendetide is indicated for use in immunoscintigraphy in patients with known colorectal or ovarian cancer. Indium In 111 satumomab pendetide helps determine the extent and location of extrahepatic foci of disease, and can be helpful in the preoperative determination of the resectability of malignant lesions in these patients. It helps clarify equivocal results of, and serves to complement, other diagnostic evaluations. ^{{01} {04} {05} {06} {08} {10} {17} {18} {19} {20} {21} {22} {23} {24} {25} {26} {27} {28} {29} {35}}
—Indium In 111 satumomab pendetide immunoscintigraphy, when combined with computed tomography (CT) scans results and carcinoembryonic antigen (CEA) or serum tumor marker levels, provides complementary information useful in the presurgical evaluation of colorectal or ovarian cancer patients. ^{{05} {06} {18} {19} {20} {21} {22} {23} {24} {25} {26} {27} {28} {29} {35}}

Unaccepted
Not indicated as a screening test for ovarian or colorectal cancer. ^{{01} {35}}


Physical Properties

Nuclear data: ^{01}

Radionuclide (half-life)	Mode of decay	Principal photon emissions (keV)	Mean number of emissions/ disintegration
In 111 (2.83 days)	Electron capture	Gamma (171.3)	0.90
		Gamma (245.4)	0.94

Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

The murine monoclonal antibody of the immunoglobulin subclass IgG ₁, satumomab (MAb B72.3), localizes or binds specifically to a tumor-associated glycoprotein (TAG-72), a cell surface antigen expressed at high levels on nearly all colorectal and ovarian adenocarcinomas. The monoclonal antibody B72.3 is site-specifically labeled with indium In 111 chloride using the linker-chelator, glycyl-tyrosyl-(N,epsilon-diethylenetriaminepentaacetic acid)-lysine or GYK-DTPA. The resultant radiolabeled monoclonal antibody conjugate, ¹¹¹In satumomab pendetide (CYT-103), retains the immunoreactivity of the unconjugated monoclonal antibody. Following intravenous administration, the indium In 111–labeled satumomab pendetide travels through the bloodstream until it encounters tumors bearing the TAG-72 antigen. The distribution of radioactivity is recorded by imaging. ^{{01} {04} {05} {06} {07} {08} {12} {14} {16} {17} {35}}

Distribution:

Following intravenous administration, indium In 111 satumomab pendetide localizes rapidly in colorectal adenocarcinomas and common epithelial ovarian carcinomas. In in vitro immunohistologic studies indium In 111 satumomab pendetide has been reported to be reactive with the majority of breast, non–small cell lung, pancreatic, gastric, and esophageal carcinomas. ^{{01} {32} {35}} Some non-antigen-dependent localization occurs, probably secondary to catabolism, in normal liver, spleen, and bone marrow. ^{{07} {33} {34}} In some individuals, some radioactivity may localize in the bowel, blood pool, kidneys, urinary bladder, male genitalia, and breast nipples in women. ^{{01} {04} {07} {12} {15} {32}}

Half-life:

Elimination—56±14 hours (mean±SD). ^{{01} {07} {15} {35}}

Time to radioactivity visualization:

Optimal diagnostic images—48 to 72 hours. ^{{01} {06}}

Note: Variability occurs; diagnostic images have been obtained as early as 24 hours and as late as 120 hours after administration of the radiopharmaceutical. ^{01} Delayed imaging allows clearance of the radiopharmaceutical from the cardiac and vascular pool, which improves image contrast. ^{07}


Radiation dosimetry:
^{01}

Estimated absorbed radiation dose *
Organ	mGy/MBq	rad/mCi
Spleen	0.86	3.2
Liver	0.81	3.0
Red marrow	0.65	2.41
Kidney	0.52	1.93
Lungs	0.26	0.96
Adrenal	0.24	0.89
Pancreas	0.20	0.74
Bone	0.18	0.67
Heart wall	0.17	0.63
Stomach wall	0.17	0.63
Large intestine wall (upper)	0.17	0.63
Small intestine	0.16	0.59
Ovaries	0.16	0.59
Bladder	0.15	0.56
Uterus	0.15	0.56
Large intestine wall (lower)	0.14	0.52
Other tissues	0.12	0.44
Skin	0.09	0.33
Thyroid	0.08	0.30
Testes	0.08	0.30
Total body	0.15	0.55
Effective dose: 0.32 mSv/MBq (1.2 rem/mCi) {35}

^* For adults; intravenous injection. Includes absorbed radiation doses from both the indium In 111 and the indium In 114 contaminant. The maximum permissible level (0.16% at expiration time) of indium In 114 was used for dose estimates. ^{01}

Elimination:
    Renal (10% of the administered activity excreted within 72 hours). ^{{01} {07} {15} {35}}

Note: The radioligand is excreted in the urine as a small molecular weight entity, which indicates that the indium In 111 has become catabolized from the immunoglobulin molecule. ^{{07} {35}}



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to murine antibody–based products may be sensitive to indium In 111 satumomab pendetide also. ^{01}

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of indium In 111 satumomab pendetide have not been performed. ^{01}

Pregnancy/Reproduction

Pregnancy—
Indium In 111 crosses the placenta. Studies have not been done with indium In 111 satumomab pendetide in humans.

The possibility of pregnancy should be assessed in women of child-bearing potential. Clinical situations exist where the benefit to the patient and fetus, based on information derived from radiopharmaceutical use, outweighs the risks from fetal exposure to radiation. In these situations, the physician should use discretion and reduce the radiopharmaceutical dose to the lowest possible amount.

Studies have not been done in animals.

FDA Pregnancy Category C. ^{01}

Breast-feeding

In some women, indium In 111 satumomab pendetide has been found to localize in breast nipples. Because of the potential risk to the infant from radiation exposure, temporary discontinuation of nursing is recommended. ^{{01} {04} {35}}

Pediatrics

There have been no specific studies evaluating the safety and efficacy of indium In 111 satumomab pendetide in pediatric patients. When this radiopharmaceutical is used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation.


Geriatrics


Diagnostic studies performed to date using indium In 111 satumomab pendetide have not demonstrated geriatrics-specific problems that would limit the usefulness of indium In 111 satumomab pendetide in the elderly. ^{{04} {05} {06} {30}}


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 other diagnostic test results
Immunoassays, including carcinoembryonic antigen (CEA) and serum tumor marker (CA 125)    (human anti-murine antibodies [HAMAs] production may be induced by the administration of indium In 111 satumomab pendetide; HAMAs in serum may cause falsely elevated values of in vitro immunoassays; interference may persist for months; use of non-murine immunoassays, or HAMAs removal by adsorption, blocking, or heat inactivation is recommended to avoid interference ^{{01} {05} {09} {13} {35}})


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 medications
Murine antibody–based products    (previous administration of murine antibody–based products, including this agent, may induce human anti-murine antibodies [HAMAs], which may alter the clearance and tissue biodistribution of indium In 111 satumomab pendetide; however, more studies are needed to establish the effects of circulating HAMAs on monoclonal antibody–based products ^{{01} {05} {09} {31}})


Due to medical problems or conditions
Aneurysms, abdominal or
Bowel adhesions, postoperative or
Colostomy or
Inflammatory lesions, local or
Joint disease, degenerative or
Ovarian tumors, benign    (localization of indium In 111 satumomab pendetide may occur at these sites ^{{01} {03} {35}})


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 problem exists
Sensitivity to murine antibody–based products or to the radiopharmaceutical preparation^{01}


Side/Adverse Effects
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
Incidence less frequent
    
Fever^{01}{05}{18}

Incidence rare
    
Allergic reaction, including anaphylaxis
    
chest pain
    
confusion
    
hypertension
    
hypotension
    
hypothermia
    
skin rash^{{01}{04}{05}{13}}



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Chills
    
diarrhea
    
dizziness
    
flushing of skin
    
headache
    
joint pain
    
nausea
    
nervousness^{{01}{05}{13}{14}}





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 at sites of tumor spread or growth

Tumor sites may be visualized by external imaging

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

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

Pregnancy—Indium In 111 crosses placenta; risk to fetus from radiation exposure as opposed to benefit derived from use should be considered





Breast-feeding—Indium In 111 satumomab pendetide may be distributed into breast milk; temporary discontinuation of nursing recommended because of risk to infant from radiation exposure





Use in children—Risk of radiation exposure as opposed to benefit derived from use should be considered


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

Administration of a laxative, before imaging, to minimize imaging interference due to radioactivity localization in stool ^{01}


Side/adverse effects
Signs of potential side effects, especially allergic reactions including anaphylaxis, fever, chest pain, confusion, hypertension, hypotension, hypothermia, skin rash


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 authorized by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority.

Laxative administration prior to initial or follow-up images is recommended to minimize radioactivity in bowel, which is due to uptake of isotope in stool and which may interfere with image interpretation. ^{{01} {04} {15} {35}}

Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. ^{36}

For treatment of adverse effects
Epinephrine, antihistamines, and corticosteroid agents should be available during the administration of indium In 111 satumomab pendetide because of the possibility of allergic reactions. ^{01}


Parenteral Dosage Forms

INDIUM In 111 SATUMOMAB PENDETIDE INJECTION

Usual adult and adolescent administered activity
For diagnosis of extrahepatic disease—Intravenous, 1 mg of satumomab pendetide radiolabeled with 185 megabecquerels (5 millicuries) of indium In 111 chloride, administered over a period of five minutes. ^{{01} {04} {05}}

Usual pediatric administered activity
Safety and efficacy have not been established. ^{{01} {35}}

Usual geriatric administered activity
See Usual adult and adolescent administered activity .

Strength(s) usually available
U.S.—


1 mg of satumomab pendetide per 2 mL-single-dose vial of sodium phosphate–buffered saline solution (Rx) [OncoScint CR/OV]

Canada—
Not commercially available.

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

Note: Product should be brought to room temperature before radiolabeling.
After radiolabeling, injection may be kept at room temperature, up to 8 hours, until administration. ^{01}


Preparation of dosage form:
To prepare injection, a sterile, pyrogen-free indium In 111 chloride solution is used. Isoptope solution must be buffered with sodium acetate before adding to the satumomab pendetide solution. See manufacturer's package insert for instructions. ^{{01} {35}}

Stability:
Injection should be administered within 8 hours after radiolabeling. ^{01}

Note: Caution—Radioactive material.

Revised: 08/02/1994

References

1. OncoScint CR/OV package insert (Cytogen—US), Rev 12/30/92.
   

2. USP Radiopharmaceuticals Panel meeting on 08/04/92.
   

3. Abdel-Nabi HH, Chan HW, Doerr RJ. Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma. J Nucl Med 1990; 31(12): 1975-9.
   

4. Abdel-Nabi HH, Chan HW, Doerr RJ, et al. In-111-labeled monoclonal antibody immunoscintigraphy in colorectal carcinoma: safety, sensitivity, and preliminary clinical results. Radiology 1990; 175: 163-71.
   

5. Doerr RJ, Abdel-Nabi HH, Krag D, et al. Radiolabeled antibody imaging in the management of colorectal cancer. Ann Surg 1991; 214(2): 118-24.
   

6. Doerr RJ, Abdel-Nabi HH, Baker JM, et al. Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3. Arch Surg 1990; 125: 1601-5.
   

7. Harwood SJ, Carroll RG, Webster WB, et al. Human biodistribution of ¹¹¹In-labeled B72.3 monoclonal antibody. Cancer Res 1990; (Suppl) 50: 932S-936S.
   

8. Neal CE, Swan TL, Baker MR, et al. Immunoscintigraphy of colorectal carcinoma utilizing ^{11 1}In-labeled monoclonal antibody conjugate CYT-103. Gastrointest Radiol 1991; 16: 251-5.
   

9. Price T, Beatty BG, Beatty JD, et al. Human anti-murine antibody interference in measurement of carcinoembryonic antigen assessed with a double-antibody enzyme immunoassay. Clin Chem 1991; 37(1): 51-7.
   

10. Serafini AN, Vargas-Cuba R, Benedetto P, et al. Clinical experience in utilizing radiolabeled monoclonal antibodies. Antibody, Immunoconjugates, and Radiopharmaceuticals 1991; 4(1): 77-83.
    

11. Task Group of Committee 2 of the International Commission on Radiological Protection. Annals of the ICRP. ICRP Publication 53—Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988: 234.
    

12. Sands H, Jones PL. Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor. J Nucl Med 1987; 28: 390-8.
    

13. Hansen H, et al. Solving the problem of antibody interference in commercial ``sandwich''-type immunoassays of carcinoembryonic antigen. Clin Chem 1989; 35: 146-51.
    

14. Johnson VG, Schlom J, Paterson AJ, et al. Analysis of human tumor-associated glycoprotein (TAG-7) identified by monoclonal antibody B72.3. Cancer Res 1986; 46: 850-7.
    

15. Yokoyama K, Carrasquillo JA, Chang AE, et al. Differences in biodistribution of indium-111 and iodine-131 labeled B72.3 monoclonal antibodies in patients with colorectal cancer. J Nucl Med 1989; 30: 320-7.
    

16. Abdel-Nabi H, Croghan G, Doerr RJ. Relationship between tumor expression of TAG-72 and tumor imaging with In-111 labeled B72.3 MoAb. J Nucl Med 1989; 30: 908.
    

17. Colcher D, Estevan JM, Carrasquillo SA, et al. Complementation of intracavitary and intravenous administration of monoclonal antibody (B72.3) in patients with carcinoma. J Cancer Res 1987; 47: 4218-24.
    

18. Maguire R, Pascucci V, Maroli A, et al. Immunoscintigraphy of colorectal adenocarcinoma: multicenter clinical trials with ^{11 1}In-CYT-103. Presented at Fifth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1990.
    

19. Weiner GJ, Kahn D, Jochimsen PR, et al. The clinical impact of imaging with ^{11 1}In B72.3 on the management of patients with potentially resectable recurrent colorectal adenocarcinoma. Presented at Sixth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1991.
    

20. Gallion HH, Pavlik EJ, Surwit RD, et al. The efficacy of ^{11 1}In-CYT-103 immunoscintigraphy prior to second look laparotomy in patients with epithelial ovarian cancer. Presented at American College of Obstetricians and Gynecologists, New Orleans, May 1991.
    

21. Gallup D, Serafini A, Vargas-Cuba R, et al. Intravenously administered ^{11 1}In-CYT-103 in the imaging of ovarian carcinoma—correlative findings with standard imaging, surgery and pathology. Presented at American College of Obstetricians and Gynecologists, New Orleans, May 1991.
    

22. Krag DN, Ford P, Smith L, et al. Clinical immunoscintigraphy (IS) of ovarian cancer with ^{11 1}In-CYT-103. Presented at Sixth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1991.
    

23. Collier BD, Abdel-Nabi H, Doerr R, et al. Detection of colorectal cancer with In-111-labeled CYT-103. Presented at 76th Annual Meeting Radiological Society of North America, Chicago, November 1990.
    

24. Kaplan EH, Hartman DD, Fordham EW, et al. ^{11 1}Indium-labeled monoclonal antibody (MoAb), ^{11 1}In-CYT-103, imaging of colorectal carcinoma: a surgical correlation. Presented at American Society of Clinical Oncology, Washington, DC, May 1990.
    

25. Pascucci VL, Maguire RT, Maroli AN, et al. Comparison of ^{11 1}In-CYT-103 (OncoScint CR 103) immunoscintigraphy and CT imaging in presurgical colorectal cancer patients. Presented at Fifth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1990.
    

26. Serafini AN, Gallup DG, Vargas-Cuba R, et al. Detection of ovarian carcinoma with radiolabeled monoclonal antibody In-111 CYT 103. Presented at 76th Annual Meeting Radiological Society of North America, Chicago, November 1990.
    

27. Surwit E, et al. Use of radiolabeled immunoconjugate of MAb B72.3 (In-111 CYT 103) for the detection of epithelial ovarian adenocarcinoma. Presented at Fifth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1990.
    

28. Pavlik EJ, Gallion HH, Ryo U, et al. In-111 CYT 103 monoclonal antibody for abdominal localization of ovarian and colorectal carcinoma by SPECT of planar imaging. Presented at Fifth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, March 1990.
    

29. Maguire R, Pascucci V, Maroli A, et al. Radioimaging with In-111 CYT-103: effect on the presurgical management of colorectal cancer patients. Presented at American Society of Clinical Oncology, May 1990.
    

30. Abdel-Nabi H, Herrera L, Evans N, et al. In-111 CYT-103 MoAb imaging in patients with suspected recurrent colorectal cancer (RCC). Presented at 38th Annual Meeting of the Society of Nuclear Medicine, Cincinnati, June 1991.
    

31. Reynolds JC, Del Vecchio S, Sakahara H, et al. Anti-murine antibody response to mouse monoclonal antibodies: clinical findings and implications. Nucl Med Biol 1988; 16: 121-5.
    

32. Thor A, Noriaki O, Szpak C, et al. Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3. Cancer Res 1986; 46: 3118-24.
    

33. Harwood SJ, McDonald LM, Elkin MC, et al. Biodistribution differences of In-111 B72.3 MoAb in nude mice and man. J Nucl Med 1988; 29: 2029.
    

34. Meares CF, McCall MJ, Deshpande SV, et al. Chelate radiochemistry: clevable linkers lead to altered levels of radioactivity in the liver. Int J Cancer 1988; 2(Suppl): 99-102.
    

35. Reviewers' comments as per 02/08/93 monograph revision.
    

36. Reviewers' responses to Ballot of 5/11/94.
    

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