Arcitumomab - CEA-Scan; carcinoembryonic antigen monoclonal antibody Fab’ fragment–Technetium-99m radioimmune conjugate; IMMU-4 Fab’–Tc 99m
Status: discontinued/withdrawn in 2005
Organizations involved:
Immunomedics, Inc. – Manuf.; R&D; Tech.; USA mark.; Europe mark.
AMERISOURCEBERGEN CORP. – USA Mark.
Syncor International, Inc. – USA mark.
Pharmacia Corp. – Manuf. other
Prizer Corp. – Parent co.
Lilly, Eli & Co. – Europe mark.
Mallinckrodt Inc. – Former inv.
Hoffmann-La Roche Ltd. – Patent dispute
Teva Pharmaceutical Ind. Ltd. – Latin Amer. mark..
Cross ref: See the entry (#304) for CEA Mab, conc. or Immu-4 Bulk (For Further Manufacturing Use), the intermediate used for manufacture of this product. See the entry for Monoclonal Antibodies (#300).
Description: CEA-Scan is a lyophilized (freeze-dried) formulation of arcitumomab (IMMU-4 Fab’) or reduced Fab’ fragments of the murine ascites cultured IgG1 monoclonal antibody IMMU-4 with specificity for carcinoembryonic antigen (CEA), a protein expressed by colorectal and many other tumors, used to prepare Tech-netium Tc 99m arcitumomab for radiodiagnostic imaging of tumors. IMMU-4 F(ab’)2 fragments prepared from the IMMU-4 monoclonal antibody (Manufactured by Charles River Div., Wilmington Partners, L.P.; see the CEA Mab, conc. entry, #304) by pepsin digestion are further chemically cleaved and reduced to provide the IMMU-4 Fab’ fragment with exposed sulfhydryl (-SH) groups (arcitumomab; IMMU-4 Fab’-SH; actived agent in CEA-Scan) capable of forming covalent links with the metal radioisotope Technetium-99m. Arcitumomab has a molecular weight of ~54,000 Daltons (~54 kDa). Arcitumomab is used in the local nuclear pharmacy for the preparation of the radioimmune conjugate, Technetium Tc 99m arcitumomab, used for radiodiagnostic imaging of colorectal tumors.
The IMMU-4 murine monoclonal antibody (originally called NP-4), an IgG1 antibody with a lambda light chain, was derived from the IMMU-4 hybridoma cell line, which was first isolated in 1981 from the fusion of spleen cells from mice immunized with carcinoembryonic antigen (CEA) with murine myeloma cells. IMMU-4 is manufactured by Charles River Laboratories by culture of IMMU-4 hybridoma cells using the ascites method, i.e., the cells are cultured in vivo in murine ascites (peri-to-neal sac or gut) fluid. See the entry (#304) for CEA Mab, conc. or IMMU-4 Bulk (For Further Manufacturing Use). This IMMU-4 Bulk is exclusively supplied to Immunomedics, Inc. IMMU-4 monoclonal antibodies are purified from the ascitic fluid, and digested with pepsin to produce IMMU-4 F(ab’)2 fragments, which are reductively cleaved, e.g., with cysteine, to produce the Fab’ fragment with pendent sulfhydryl groups (arcitumomab; IMMU-4 Fab’-SH).
In the on-site or local nuclear pharmacy, IMMU-4 Fab’-SH (arcitumomab) is conjugated or radiolabeled with Technetium-99m, a radioactive isotope, by mixing IMMU-4 Fab’-SH with 25 to 30 mCi sodium pertechnetate Tc 99m (99m-pertechnetate) in the presence of stannous (tin) ions to form Technetium Tc 99m arcitumomab or Technetium Tc 99m CEA-Scan, and purified by Instant Thin Layer Chromatography (ITLC). Prior to patient administration, radiochemical purity must be >90% by ITLC. The Technetium Tc 99m CEA-Scan is then administered systemically for radioimaging purposes.
CEA-Scan is packaged as a single-use vial containing 1.25 mg lyophilized arcitumomab, along with 0.29 mg stannous chloride, plus excipients – potassium sodium tartrate tetra-hydrate, sodium acetate trihydrate, sodium chloride, glacial acetic acid, hydrochloric acid, and sucrose. The product contains no preservatives. The dating period is 24 months from the date of manufacture, defined as the date of final sterile filtration of the bulk, when stored at 2-8˚C (refrigerated). Following reconstitution (aqueous dissolution) of the lyophilized arcitumomab and radiolabeling, the material can be held at room temperature and must be used within four hours. In the nuclear pharmacy, the final imaging agent, Technetium Tc 99m Arcitumomab, is formed by reconstitution of the contents of the CEA-Scan vial with 30 mCi of Tc 99m sodium pertechnetate in 1 ml of Sodium Chloride for Injection, USP. The resulting solution is pH 5-7 for intravenous use only. Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours.
Nomenclature: CEA Mab Fab'–Tc 99m radioconj. [BIO]; CEA-Scan [TR]; arcitumomab [FDA USAN INN]; immunoglobulin G 1 (mouse monoclonal IMMU-4 Fab’ fragment gamma-chain anti-human antigen CEA), disulfide with mouse monoclonal IMMU-4 light chain, technetium-99mTc salt [CAS for radiolabeled arcitumomab]; immunoglobulin G 1 (mouse monoclonal IMMU-4 Fab’ fragment gamma-chain anti-human antigen CEA), disulfide with mouse monoclonal IMMU-4 light chain [CAS for arcitu-momab]; 154361-48-5 [CAS RN for arcitumomab]; 154361-49-6 [CAS RN for Tc-labeled arcitumomab]; technetium Tc99m arcitumomab [SY]; IMMU-4 Fab’ [SY]; ImmuRAID-Tc-99m [SY]; ImmuRAID-CEA-Tc-99m [SY]; NP-4 [SY original name of IMMU-4 cell line]; Fab’-SH [SY for arcitumomab]; F(ab’)2-SH fragment [SY for arcitu-momab]; carcinoembryonic antigen monoclonal antibody Fab’ fragment–Technetium-99m radioimmune conjugate [SY for arcitu-momab]
Biological.: IMMU-4 monoclonal antibody and its functional fragments have binding specificity for carcinoembryonic antigen (CEA), a tumor-associated antigen. The CEA target antigen is a heavily glycosylated membrane-bound glycoprotein secreted by virtually all solid tumors with a molecular weight of 180-200 kDa. CEA exhibits marked heterogeneity due to quantitative and qualitative differences in its carbohydrate composition (glycosylation). Cellular expression of CEA is increased in a variety of carcinomas, particularly of the gastro-intestinal tract, as well as in fetal gastrointestinal tissues and in certain inflammatory states (e.g., Crohn’s disease, inflammatory bowel disease, post-radiation therapy to the bowel). Studies have shown that immunohistochemical staining of a variety of adenocarcinomas with CEA antibodies and elevated serum CEA levels are often associated with carcinomas of the colon, stomach, rectum, pancreas, and lungs. Immunoassays of serum levels of circulating CEA are often performed to obtain prognostic information following potentially curative surgical resection of tumors, and as an adjunct to monitoring for recurrent disease in patients who have undergone curative resection of colorectal cancer. Various cross-reactive, but genetically distinct, CEA variants have been described in the literature, including nonspecific cross-reactive antigen (NCA) and meconium antigen (MA). However, IMMU-4 is specific for the classical ~200,000 Dalton (200 kDa) CEA molecule found predominantly on the tumor cell membrane, and does not cross-react with NCA or MA. The Ka determined on 8 lots of arcitu-momab was 3-9 x 107/M.
In proteins containing disulfide bonds, such as the IMMU-4 Mab F(ab’)2 fragment of the IMMU-4 immunoglobulin (monoclonal antibody) molecule, the disulfide bonds can be reductively cleaved to dissociate the F(ab’)2 protein into smaller fragments. The IMMU-4 Fab’-SH fragment is formed by the reductive cleavage of IMMU-4 monoclonal antibody (IgG) F(ab’)2 fragments using cysteine, a disulfide-reducing agent, to form Fab’ fragments. The IMMU-4 F(ab’)2 is reduced to provide fragments with exposed/pendant sulfhydryl groups capable of forming stable covalent bonds with Technetium-99m radioisotope ligand (99m-per-technetate). The cleaved F(ab’)2 fragments containing at least one free sulfhydryl group are termed “Fab’-SH.” With its free pendant sulfhydryl groups, Fab’-SH can selectively bind certain radioactive metals, e.g., Technetium Tc 99m, forming radio--immune conjugates, with the metal ions tightly bound covalently to the sulfhydryl groups, with the radio--immune conjugates stable in blood and other bodily fluids and tissues. In the nuclear pharmacy, addition of the resultant Fab’-SH fragment to reduced Technetium-99m pertechnetate results in binding of all of the reduced pertechnetate to the Fab’-SH, forming the final radioimmune conjugate.
Removal of the Fc portion of the IgG molecule (monoclonal antibody) eliminates much of the immunogenicity ordinarily observed with mouse-derived antibodies, i.e., reduces induction of human anti-mouse antibodies (HAMA), which has serious adverse effects. Use of just the smaller Fab’ fragment also facilitates rapid clearance of CEA-SCAN and more pronounced tumor/background radiation ratios. Using CEA-SCAN, ordinary SPECT imaging systems can identify tumors as small as 0.3 cm, although the actual resolution with planar gamma cameras is usually above 1 cm. The arcitu-momab Fab’ fragment also binds to 99mTc using a simple, one-step, one-vial, direct radiolabeling method. In contrast, whole IgG (monoclonal antibody) imaging products, e.g., OncoScint (see related entry), are eliminated much slower than arcitu-momab, and can not be used with 99mTc and other radionuclides with relatively short half-lives (i.e., use indium-111 or iodine-121, with considerably longer half-lives).
After intravenous injection, Tech-netium Tc 99m arcitumomab complexes (binds to) circulating CEA. Less than 50% complexation was observed with plasma CEA levels up to 2000 ng/mL, and is not detectable at serum CEA levels below 250 ng/mL. The remaining Tech-netium Tc 99m arcitumomab binds to CEA on the cell surface (of tumors), the desired activity. The pharmacokinetics of the Fab’ fragment (as compared to the intact immunoglobulin) minimizes liver metabolism. The Fab’ fragment clears rapidly from the blood.
Companies.: CEA-Scan was developed and manufactured by Immunomedics, Inc., CBER/FDA est. no. 1205. On Dec. 17, 1998, Immunomedics announced FDA approval of the company’s new manufacturing facility in Morris Plains, NJ. Prior to this, manufacturing was performed at its Newark, NJ facility. Pharmacia Inc. (Albuquerque, NM; merged into Pfizer) formulated, filled and lyophilized the final containers under a shared manufacturing agreement (reported at time of approval).
In Aug. 2005, Immunomedics announced discontinuation of CEA-Scan due to low sales.
Immunomedics and Bergen Brunswig Specialty Company, a wholly owned subsidiary of Bergen Brunswig Corp., now AMERISOURCEBERGEN CORP., co-marketed CEA-Scan in the U.S. Prior to April 1998, Mallin-ckrodt, Inc. was Immunomedics’ U.S. and European co-marketer for the product. Immunomedics marketed CEA-Scan in Germany, France, and the U.K. through its own sales organizations, and through distributors in Spain, Italy, Greece and Belgium. CEA-Scan was co-marketed in European countries by Eli Lilly & Co. Merck Frosst, a subsidiary of Merck & Co., originally licensed Canadian rights, but these were returned.
Syncor International, Inc., the leading U.S. provider of radio-pharmaceutical services, in Sept. 1998 began making CEA-Scan available to its hospital and clinic accounts across the U.S., supported by Immunomedics’ sales and technical support specialists. Syncor provided Technetium-99m arcitumomab (the final radioimmune conjugate) as an already radiolabeled, ready to inject preparation; and supported Immu-nomedics’ promotional effort with its own sales force, as well as with the radiopharmacists at its 118 U.S. facilities.
Teva-Tuteur, a subsidiary of Teva Pharmaceutical Industries Ltd., had marketing rights in Latin American countries.
Manufacture: The source monoclonal antibody, IMMU-4, was produced in ascitic fluid (ascites method), involving culturing IMMU-4 hybridoma cells in vivo in the mouse peritoneal cavity (gut). The injection of the mice and collection and centrifugation of the ascitic fluid was performed by Charles River Labs. under a shared manufacturing agreement. At Immunomedics, the ascitic fluid from each single lot (12-14 liters) was further processed as 4 sublots of about 3 L each, with these pooled after processing to arcitumomab. First, IMMU-4 immune globulin G (IgG) was isolated from the ascitic fluid using Q-Sepharose, Protein A and S-Sepharose column chromatography. The IgG was converted to its F(ab’)2 fragment by pepsin digestion. The fragment was further purified by chromatography including use of Q-Sepharose columns. The F(ab’)2 fragment was reduced by reaction with cysteine, resulting in the Fab’-SH fragment (arcitumomab), which is further purified by exclusion HPLC. The arcitumomab was formulated (mixed) with stannous chloride in an acetate/tartrate buffer, to facilitate on-site or local nuclear pharmacy radiolabeling with Technetium Tc99m, and the product was lyophilized (freeze-dried). During formulation and filling, the solution was maintained in an argon inert gas atmosphere to prevent oxidation. The final formulation, sterile filtration, vial filling, and lyophilization, and also labeling and distribution, were performed by contractors (Pharmacia Corp.). All release testing was performed by Immunomedics.
Examination of four manufacturing lots of ascitic fluid (as reported at the time of approval) by transmission electron microscopy (TEM) indicated the presence of 0.86 x 105 to 3.94 x 105 retroviral particles/Liter. Using SV40, pseudorabies, and Muloney murine leukemia virus (MuLV) as marker viruses, the arcitumomab purification process was shown to reduce virus titers (ranges for 3 studies) by 12.7-14.4 log for MuLV, 12.6-13.2 for pseudorabies, and 6.5-8.6 for SV40.
Various quality control assays were performed on the intermediates in the purification process. IgG testing after the Q-Sepharose chromatography included IgG concentration, endo-toxin and bioburden; after Protein A chromatography includes IEF, Protein A, HPLC, SDS-PAGE, endotoxin and bioburden; and after S-Sepharose chromatography includes IEF, HPLC, isotyping, SDS-PAGE, immunoreactivity, mycoplasma, reverse transcriptase, endotoxin and bioburden. For the F(ab’), testing included IEF, HPLC, SDS-PAGE, immuno-reactivity, mouse DNA, pristane, endotoxin, and bioburden. For arcitumomab (prior to formulation), testing included IEF, HPLC, immunoreactivity, thiol groups, radiolabeling, ITLC, endo-toxin, and bioburden. The manufacturing process had been validated to remove non-product protein, mouse DNA, residual Protein A, pepsin, pristane, and had been evaluated for capacity to remove/inactivate viruses.
A Certificate of Analysis included in the product’s FDA Summary Basis of Approval (SBA) provides detailed release specifications and results for a single lot of CEA-Scan (final product). Test parameters included (with actual measurements/-values in parentheses): UV-HPLC, not less than (NLT) 90% as Fab’ (97.46%); protein content, 1.25 +/- 0.12 mg/vial (1.30 mg/vial); immunoreactivity, NLT 75% (91.25%); radiolabeling, NLT 70% as Tc-Fab’ (82.28%), not more than (NMT) 25% as Tc-F(ab’)2 (11.13%), NLT 90% combined (93.41%); ITLC, NMT 5% free 99mTc (0.34%); SDS-PAGE using Coomassie Blue Stain, a band pattern similar to that of DTNB-modified reference standard (passed); SDS-PAGE, using densito-metry under non-reducing conditions, NTL 50% for Fab’ (50 kDa region; 57.58%), NMT 45% for H’ and L’ chains combined (25 kDa region; 23.11%), and under reducing conditions, NLT 85% for H’ and L’ chains combined (25 kDa region; 98.72%); IEF, using Coomassie Blue Stain, a band pattern similar to that of DCNB-modified reference standard (passed); IEF using densitometry, 6 regions of bands between 4.8-5.8 (passed), and areas of each of the six regions (spec not presented); stannous ion content, NLT 50 µg/vial (114.6 µg/vial); endotoxin, NMT 2 EU/vial (5.93 mg/vial); sterility, sterile (passed); and moisture, NMT 5% (3.78%). CEA-Scan must pass all tests prior to release.
FDA class: Biologic PLA
CBER class: Blood And Blood Derivatives
CBER to CDER: Among the products transferred within FDA on June 30, 2003
Approvals: Date = 19960628, PLA/ELA (91-0209 and 91-0208)
Date =19981217; PLA supplement; Indication = approval of new manufacturing facility and processes
Indications: [full text from "Indications” section of product insert/labeling]:
CEA-Scan (Arcitumomab) is indicated, in conjunction with standard diagnostic evaluations (e.g., additional imaging evaluation), for detection of the presence, location and extent of recurrent and/or metastatic colorectal carcinoma involving the liver, extrahepatic abdomen and pelvis in patients with a histologically confirmed diagnosis of colorectal carcinoma. CEA-Scan provides additional information in patients with no evidence of disease by standard diagnostic modalities (SDM) in whom recurrence or metastasis is suspected based upon elevated or rising serum CEA, and in patients with evidence of metastatic or recurrent disease on SDM. A retrospective analysis suggests that these data can be useful in the evaluation of patients in whom surgical intervention (biopsy, exploratory laparotomy and surgical resection) is under consideration.
CEA-Scan is not indicated for the differential diagnosis of suspected colorectal carcinoma or as a screening tool for colorectal cancer. CEA-Scan is not intended for readministration or for assessment of response to treatment. (see PRECAUTIONS).
Status: On Aug. 31, 2005, Immunomedics announced discontinuation of CEA-Scan due to low sales. approvals, including in the U.S. and European Union, have subsequently been voluntarily withdrawn by Immunomedics.
Arcitumomab was exempt from CBER/FDA lot release inspection requirements.
On Dec. 17, 1998, Immunomedics, Inc. announced FDA approval of the its new manufacturing facility in Morris Plains, NJ, and processes for manufacture of CEA-Scan. Prior to this, product manufacturing occurred at its former Newark, NJ facility. The approval included a review of certain changes in product manufacturing processes for both CEA-Scan and LeukoScan (sulesomab; not approved in U.S.; see entry #308).
Application for European Union approval was filed with EMEA on Jan. 26, 1999, and was granted on Oct. 4, 1999. EU market authorization was withdrawn on Sept. 27, 2005 at the request of Immunomedics.
Tech. transfer: The product insert/labeling cites U.S. patents 5,514,363; 4,331,647; and 4,818,709.
U.S. patent 5,514,363 (a continuation of 5,061,641), “Method for radiolabeling antibody fragments,” Shochat, et al., May 7, 1996, assigned to Immunomedics, Inc., describes manufacture and on-site/local preparation of radiolabeled arcitumomab. The exemplary claim (no. 1) states: “A method for direct radio labeling of a monovalent antibody fragment, comprising the step of contacting, in solution, a mixture of (a) a monovalent Fab-SH, Fab’-SH or Fabc-SH monovalent antibody fragment produced by reductive cleavage, using a thiol reducing agent, of a divalent F(ab)2 or F(ab’)2 precursor fragment or whole immunoglobulin, respectively, and (b) a stannous ion reducing agent for pertechnetate or perrhenate, wherein said mixture is substantially free of low molecular weight thiol compounds, with 99m-pertechnetate, 186-per-rhenate or 188-perrhenate ions, and recovering the resultant solution of radiolabeled monovalent antibody fragment without purification.” See also EP 336678.
The only example in U.S. 5,514,363 describes final preparation of the radioconjugate: “A solution of SnCl2 is prepared by washing a piece of solid SnCl2 with 1N aqueous HCl to remove surface oxide, drying and weighing, then dissolving the solid in metal-free 10N HCl. The resultant solution is diluted with metal-free distilled water and phthalate/tartrate buffer, pH 5.5 (0.13 mg Sn/ml), filtered and purged with argon. A solution of anti-CEA-Fab’-SH is mixed with the foregoing SnCl2 solution in a ratio of 13 µg Sn/mg Fab’-SH, purged with argon, and 99m-TcO4 is then added (about 20 mCi/mg), at room temperature, and incubated about 30 min. The resultant labeled antibody solution contains nearly 100% of the label bound to Fab’, and can be used after sterile filtration through a syringe needle equipped with a sterile filter, directly for patient injection.”
In Dec. 2003, Immunomedics prevailed in a patent dispute with Hoffmann-La Roche in Europe concerning Roche’s CEA immunodiagnostic kits, with the Dutch Supreme Court ruling that Immunomedic’s patent covering arcitumomab and CEA-specific monoclonal antibodies was valid throughout the European Union, and that Immunomedic’s was entitled to a portion of profits from Roche’s sales. This followed an earlier finding by a German court that Immunomedics patent was valid. The dispute is being appealed to the European Court of Justice.
Medical: Technetium Tc 99m arcitumomab (CEA-Scan) is a nuclear imaging agent used in conjunction with standard diag-nostic evaluations, e.g., computerized tomography (CT) scans, to detect the presence, location, and extent of metastatic disease in patients with primary or recurrent cancer. CEA-Scan is particularly useful for imaging colorectal cancer and its metastases. Adding radiodiagnostic imaging with CEA-Scan to a standard preoperative workup can help identify those patients who will benefit from aggressive procedures and those for whom minimal surgery and adjuvant chemotherapy would be appropriate. CEA-Scan is administered to patients and three hours later the patient is scanned with a standard tomographic nuclear camera, which shows in two- and three-dimensional images areas of CEA concentration (likely areas of tumors).
Technetium Tc 99m arcitumomab (CEA-Scan) use has been shown in multicenter pivotal trials to be more sensitive than computerized tomography (CT) imaging or blood CEA studies (immunoassays) for the detection and evaluation of metastatic and recurrent colorectal cancer. When added to CT, use of CEA-Scan increased the preoperative identification of resectable patients by 40%, and identified twice as many non-resectable patients as CT alone.
The recommended adult dosage of CEA-Scan is a single dose of 1 mg of arcitumomab labeled with 20 to 30 mCi of Technetium Tc 99m. Following dilution of the Technetium Tc 99m arcitumomab with 1 mL of Sodium Chloride Injection, USP, the dose is administered as a 2 mL intravenous injection. Alternately, the contents of the vial may be diluted to a total volume of 30 ml with isotonic Sodium Chloride Injection, USP. Intravenous infusion of this solution is usually performed over a period of 5-20 minutes.
CEA-Scan can be injected five minutes after its reconstitution and should be used within 4 hours following reconstitution. Immediately prior to administration, the patient dose should be measured in a dose calibrator. Immunoscintigraphy, using planar and Single-Photon Emission Computed Tomography (SPECT) techniques, should be performed at 2-5 hours after injection; and selected additional/follow-up views may be obtained up to 24 hours later. Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours, emitting gamma radiation with a mean energy of 140.5 Kev.
CEA-Scan has an excellent safety profile, with potentially serious adverse events at less than 1% each. CEA-Scan is virtually non-immunogenic, with less than 1% of patients experiencing a human anti-mouse antibody (HAMA) rejection-like response, involving production of antibodies to the administered murine protein.
Disease: Colorectal cancer is the third most frequent cancer in both sexes in the U.S. and most of the Western world, accounting for over 130,000 new cases diagnosed each year and more than 55,000 deaths annually. About 60% of colorectal cancer patients develop local tumor recurrence or distant metastases, either because of spread already being present at the time of initial surgery, or because of the failure of current detection methods to identify all sites of cancer before or during surgery.
Market In Aug. 2005, Immunomedics announced discontinuation of CEA-Scan due to low sales, primarily due to competition from positron emission tomography (PET) radiodiagnostic imaging.
Sales of CEA-Scan had been dwindling as the product has been largely replaced by PET scans. Immunomedics reported total 2005 sales of $3.8 million, including CEA-Scan. This indicates that CEA-Scan sales were negligible by most pharmaceutical standards.
The 2005 Average Wholesale Price (AWP) was $1,300 vial, with Direct Cost (Manufacturer’s discount price) of $1,025.00 (Red Book, 2005). These prices were unchanged from 2004.
CEA-Scan was reimbursed by Medicare and most insurers.
Companies involvement:
Full monograph
307 CEA Mab Fab'-Tc 99m radioconj.
Nomenclature:
CEA Mab Fab' radioconj. [BIO]
CEA-Scan [TR]
arcitumomab [FDA USAN INN]
Immunoglobulin G 1 (mouse monoclonal IMMU-4 Fab' fragment gamma-chain anti-human antigen CEA), disulfide with mouse monoclonal IMMU-4 light chain, technetium-99mTc salt [CAS for radiolabeled arcitumomab]
Immunoglobulin G 1 (mouse monoclonal IMMU-4 Fab' fragment gamma-chain anti-human antigen CEA), disulfide with mouse monoclonal IMMU-4 light chain [CAS for arcitumomab]
154361-48-5 [CAS RN]
154361-49-6 [CAS RN]
Anti-Carcinoembryonic Antigen Mab radioconjugate [SY]
carcinoembryonic antigen monoclonal antibody Fab' fragment--Technetium-99m radioimmune conjugate [SY for arcitumomab]
F(ab').sub.2-SH fragment [SY for arcitumomab]
Fab'-SH [SY for arcitumomab]
IMMU-4 Fab' [SY]
ImmuRAID-CEA-Tc-99m [SY]
ImmuRAID-Tc-99m [SY]
NP-4 [SY original name of IMMU-4 cell line]
technetium Tc99m arcitumomab [SY]
FDA Class: Biologic PLA
Year of approval (FDA) = 1996
Date of 1st FDA approval = 19960628
(in format YYYYMMDD)
Index Terms:
antibodies (see also immune globulins; monoclonal antibodies)
biopharmaceutical products
conjugates
monoclonal antibodies
murine (mouse) materials used
murine (mouse) monoclonal antibodies
radioimmune conjugates<!-- radioconjugates -->
ascitic fluid
IMMU-4 hybridoma, murine
mammalian cell culture
murine ascites
rodent cells <!-- rodentcells -->
acetic acid
arcitumomab
argon
carcinoembryonic antigen (CEA) monoclonal antibody
cysteine
hydrochloric acid (HCl)
lyophilized (freeze-dried)
monoclonal antibody, carcinoembryonic antigen (CEA)
murine monoclonal antibody, carcinoembryonic antigen
pepsin digestion
potassium sodium tartrate tetrahydrate
pristane
Protein A affinity chromatography
Sepharose
sodium acetate
sodium chloride
stannous chloride
sucrose
Technetium Tc 99m sodium pertechnetate
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
catheter clearance
exempt from CBER lot release requirements
FD&C Yellow 5
North American coral snake
North American coral snake
EU000 Not yet/Never filed with EU
UM999 Not Available/Not Marketed in US
US011 Approved Formerly in US/withdrawn
EM999 Not Available/Not Marketed in EU
Copyright© 2020, Biotechnology Information Institute