Technetium Tc-99m nofetumomab merpentan

Identification

Name
Technetium Tc-99m nofetumomab merpentan
Accession Number
DB09336
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Technetium Tc-99m nofetumomab merpentan (Tc-99m nm) consists of a Fab fragment of an IgG2b of the pancarcinoma murine antibody NR-LU-10.[1] The NR-LU-10 antibody is directed against a 40 kDa glycoprotein antigen expressed in a variety of cancers and some normal tissues.[Label] Tc-99m nm was developed by Boehringer Ingelheim Pharma KG and FDA approved on September 14, 1992. It was after discontinued on August 13, 2013, but in the 2018 FDA submission list, it can be found as a substance type II (Drug substance) with an active status.[8, 9]

Synonyms
  • Nofetumomab
  • Technetium (99mTc) nofetumomab merpentan
  • Technetium Tc 99m nofetumomab merpentan
Categories
Not Available
UNII
9UFH75HT7S
CAS number
165942-79-0
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Tc-99m nm is one of the technetium-labeled antibodies and it is indicated for the detection of small-cell lung cancer.[3] The small cell lung cancer is a syndrome characterized by the abnormal and uncontrolled cell growth and it is characterized by a shorter doubling time, higher growth fraction and earlier development of metastases.[4]

Pharmacodynamics

Studies have shown that the Fab fragment presents high immunoreactivity in small cell lung cancer tumors. The adenocarcinomas of the kidney and pancreas are not detected. This lack of diagnostic detection can be explained because some radioactivity gets accumulated in the excretion pathway, in nonspecific vascular locations and in non-tumor areas with traces of inflammation, increased vascular pool or recent surgical. Therefore, the detection rate may be reduced in those areas and its adjacent zones.[Label]

Mechanism of action

The mechanism of action in Tc-99m nm is ruled by the presence of nofetumomab, which can recognize the pancarcinoma antigen EpCAM and/or CD20/MS4A1,[2] and merpentan, that acts as a linker for the binding of technetium.[6]

TargetActionsOrganism
AEpithelial cell adhesion molecule
binder
Human
AB-lymphocyte antigen CD20
binder
Human
Absorption

After intravenous administration, Tc-99m nm presents a rapid distribution phase.[Label]

Volume of distribution
Not Available
Protein binding

There are no reports of binding of Tc-99m nm to binding proteins.[Label]

Metabolism
Not Available
Route of elimination

The primary route of elimination is renal and accounts for the 64% of the administered dose. After renal clearance, the main route is hepatobiliary. All the different elimination pathways lead to accumulation of radioactivity on the kidney, urinary bladder, gall bladder and intestines.[7]

Half life

The radioactive half-life of the Tc-99m nm is of 6 hours. It is important to consider this short half-life as the use of this agent should be done within the active time.[5] Tc-99m nm presents a serum half-life of 1.5 hours and an elimination phase half-life of 10.5 hours.[7]

Clearance
Not Available
Toxicity

Long-term preclinical studies to determine the carcinogenic, mutagenic or fertility effect have not been studied.[Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Breitz HB, Tyler A, Bjorn MJ, Lesley T, Weiden PL: Clinical experience with Tc-99m nofetumomab merpentan (Verluma) radioimmunoscintigraphy. Clin Nucl Med. 1997 Sep;22(9):615-20. [PubMed:9298295]
  2. Honjo T., Alt F. and Neuberger M. (2004). Molecular biology of B cells. Elsevier .
  3. Technetium radiopharmaceutical chemistry [Link]
  4. Cancer [Link]
  5. Pharmacopeia [Link]
  6. Pharmacological science [Link]
  7. National Public library [Link]
  8. FDA CDER list [Link]
  9. FDA Submission [Link]
External Links
PubChem Substance
347910442
FDA label
Download (1.32 MB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
Radioactivity (mCi/mL)30FDA label
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Protein complex binding
Specific Function
May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier...
Gene Name
EPCAM
Uniprot ID
P16422
Uniprot Name
Epithelial cell adhesion molecule
Molecular Weight
34932.005 Da
References
  1. Honjo T., Alt F. and Neuberger M. (2004). Molecular biology of B cells. Elsevier .
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Honjo T., Alt F. and Neuberger M. (2004). Molecular biology of B cells. Elsevier .

Drug created on November 26, 2015 17:09 / Updated on November 02, 2018 07:01