Mangafodipir

Identification

Summary

Mangafodipir is an organ-specific paramagnetic contrast agent indicated for the imaging of the hepatobiliary system and detecting lesions in the liver and pancreas.

Generic Name

Mangafodipir

DrugBank Accession Number

DB06796

Background

Mangafodipir is a contrast agent used as a diagnostic tool administered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver and pancreas. This drug is made up of paramagnetic manganese (II) ions combined with the chelating agent fodipir (dipyridoxyl diphosphate, DPDP). Manganese absorption into the tissues that makes the normal tissue appear brighter in MRI is limited in abnormal or cancerous tissue. Enhanced contrast by mangafodipir improves visualization and detection of lesions of the liver formed from metastatic disease or hepatocellular carcinomas. The contrast agent is present as mangafodipir trisodium marketed under the name Teslascan. Teslascan has been removed from the Drug Product List by FDA in 2003, and withdrawn from the European market in 2012.

Type

Small Molecule

Groups

Approved, Investigational, Withdrawn

Structure

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Similar Structures

Structure for Mangafodipir (DB06796)

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Weight

Average: 691.382
Monoisotopic: 691.06142

Chemical Formula

C₂₂H₃₀MnN₄O₁₄P₂

Synonyms

• Mangafodipir

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Pharmacology

Indication

Indicated for use as an organ-specific paramagnetic contrast agent developed for imaging of the hepatobiliary system and detecting lesions in liver and pancreas.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Diagnostic agent	Hepatic lesions		••••••••••••			•••••••••

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Pharmacodynamics

Manganese (II) metals exhibit paramagnetic properties that increases contrast between normal liver parenchyma and metastatic liver lesions after uptake into the hepatic or pancreatic parencyma. They serve to increase the signal intensity of liver or pancreas tissue. Enhancement in both organs is near maximal for up to approximately 4 hours after the end of administration. Lesion-related enhancement of certain types of lesions, such as liver metastases and hepatocellular carcinomas, may be detectable for up to 24 hours ⁸.

Mechanism of action

After intravenous administration, the chelate dissociates slowly to manganese and organic ligand fodipir (dipyridoxyl diphosphate), and manganese is taken up by the hepatocytes with high affinity and selectivity. The ligand fodipir is distributed to the extracellular fluid and later eliminated via urine ³. Mangafodipir shortens the longitudinal relaxation time (T1) of targeted tissues during MRI, where signal intensity or brightness is increased in normal liver parenchyma. Overall, there is increased contrast between normal tissue and abnormal tissue with lesions because there is a difference between cellular compositions ⁶, and manganese uptake in metastatic tissue or focal lesions is minimal or nearly absent ¹.

Absorption

Mangafodipir is taken up by the liver and pancreas where the contrast enhancement effect is mediated.

Volume of distribution

The volume of distribution for manganese is between 0.5 and 1.5 l/kg, and 0.17 to 0.45 l/kg for fodipir (dipyridoxyl diphosphate) ⁸. Fodipir is distributed rapidly throughout the body with the highest concentrations in the kidneys, lung, blood and liver with a low affinity in the myocardium and brain. Manganese is initially distributed to the kindeys and sequentially to liver, spleen and pancreas ⁹.

Protein binding

The protein binding of manganese is approximately 27% but negligible for fodipir ⁸. Manganese is transported to the liver via α2-macroglobulin and to a lesser extent, albumin ³.

Metabolism

Mangafodipir (MnDPDP) is dephosphorylated to form Mn dipyridoxyl monophosphate (MnDPMP) and fully dephosphorylated Mn dipyridoxyl ethylenediamine diacetate (MnPLED) in a sequential manner, followed by simultaneous transmetallation where maganese is exchanged for plasma zinc ⁸. Corresponsing zinc compounds are ZnDPDP, ZnDPMP and ZnPLED ³. Manganese is released from the complex to be transported to target organs.

Route of elimination

Fodipir is predominantly eliminated via urine within 24 hours where up to 25% of administered fodipir is excreted into feces. Manganese is mainly excreted into feces where renal elimination is about 15-20% of the dose ⁹.

Half-life

The mean initial plasma half-life of manganese metals is approximately 20 minutes and 50 minutes for fodipir (dipyridoxyl diphosphate, DPDP) ⁸.

Clearance

The approximate total clearance of radiolabeled mangafodipir is 3.1 mL/min kg in dogs ⁴.

Adverse Effects

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Toxicity

Common adverse effects include headache, nausea and feeling of warmth or flushing. Other uncommon side effects include hypersensitivity reactions, fever, diarrhea, vomiting, dizziness, palpitations, paraesthesia, abdominal pain, and taste sensations. There is no identified antidote in case of overdose. Mangafodipir displays embryotoxic and fetotoxic potential thus is contradindicated in pregnant patients. It is not reported to be genotoxic ⁹. LD50 in the mouse is 5 mmol/kg ⁷.

Pathways

Not Available

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Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Mangafodipir which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Mangafodipir which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Mangafodipir which could result in a higher serum level.
Acetaminophen	Acetaminophen may decrease the excretion rate of Mangafodipir which could result in a higher serum level.
Acetazolamide	Acetazolamide may increase the excretion rate of Mangafodipir which could result in a lower serum level and potentially a reduction in efficacy.

Food Interactions

No interactions found.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Mangafodipir trisodium	129FW80TG4	140678-14-4	BENFPBJLMUIGGD-UHFFFAOYSA-I

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Teslascan	Injection, solution	0.01 mmol/ml	Intravenous	Ge Healthcare As	2016-09-08	2012-08-02
Teslascan	Injection, solution	0.01 mmol/ml	Intravenous	Ge Healthcare As	2016-09-08	2012-08-02
Teslascan	Solution	37.9 mg / mL	Intravenous	Ge Healthcare	2000-09-15	2010-07-26

Categories

ATC Codes

V08CA05 — Mangafodipir

• V08CA — Paramagnetic contrast media
• V08C — MAGNETIC RESONANCE IMAGING CONTRAST MEDIA
• V08 — CONTRAST MEDIA
• V — VARIOUS

Drug Categories

• Acetates
• Acids, Acyclic
• Amines
• Coenzymes
• Compounds used in a research, industrial, or household setting
• Contrast Media
• Diagnostic Uses of Chemicals
• Diamines
• Drugs that are Mainly Renally Excreted
• Enzymes and Coenzymes
• Ethylenediamines
• Magnetic Resonance Contrast Activity
• Magnetic Resonance Imaging Contrast Media
• Paramagnetic Contrast Agent
• Paramagnetic Contrast Media
• Picolines
• Polyamines
• Pyridines

Classification

Not classified

Affected organisms

Not Available

Chemical Identifiers

UNII

N02W67RKJS

CAS number

155319-91-8

InChI Key

CXFKOLCMCRBYPL-UHFFFAOYSA-L

InChI

InChI=1S/C22H32N4O14P2.Mn/c1-13-21(31)15(5-17(23-13)11-39-41(33,34)35)7-25(9-19(27)28)3-4-26(10-20(29)30)8-16-6-18(12-40-42(36,37)38)24-14(2)22(16)32;/h5-6,31-32H,3-4,7-12H2,1-2H3,(H,27,28)(H,29,30)(H2,33,34,35)(H2,36,37,38);/q;+2/p-2

IUPAC Name

manganese(2+) ion 2-({2-[(carboxylatomethyl)({3-hydroxy-2-methyl-6-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino]ethyl}({3-hydroxy-2-methyl-6-[(phosphonooxy)methyl]pyridin-4-yl}methyl)amino)acetate

SMILES

[Mn++].CC1=C(O)C(CN(CCN(CC([O-])=O)CC2=CC(COP(O)(O)=O)=NC(C)=C2O)CC([O-])=O)=CC(COP(O)(O)=O)=N1

References

General References

1. Wang C: Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas. Acta Radiol Suppl. 1998;415:1-31. [Article]
2. Hirt D, Richardet JP, Urien S, Poupon J, Sogni P, Batteux F, Laurent A, Pavlovic S, Debray M, Treluyer JM, Weill B: Pharmacokinetic-pharmacodynamic modeling of manganese after a single intravenous infusion of mangafodipir in patients with acute alcoholic hepatitis. Ther Drug Monit. 2009 Oct;31(5):557-65. doi: 10.1097/FTD.0b013e3181affd6d. [Article]
3. Toft KG, Hustvedt SO, Grant D, Martinsen I, Gordon PB, Friisk GA, Korsmo AJ, Skotland T: Metabolism and pharmacokinetics of MnDPDP in man. Acta Radiol. 1997 Jul;38(4 Pt 2):677-89. [Article]
4. Hustvedt SO, Grant D, Southon TE, Zech K: Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration. Acta Radiol. 1997 Jul;38(4 Pt 2):690-9. [Article]
5. Eser G, Karabacakoglu A, Karakose S, Eser C, Kayacetin E: Mangafodipir trisodium-enhanced magnetic resonance imaging for evaluation of pancreatic mass and mass-like lesions. World J Gastroenterol. 2006 Mar 14;12(10):1603-6. [Article]
6. Karabacakoglu A, Adiguzel Y, Karakose S, Kayacetin E, Haykir R: Characterization of focal liver lesions: use of mangafodipir trisodium (MnDPDP)-enhanced MR images. Turk J Gastroenterol. 2006 Sep;17(3):164-71. [Article]
7. Colet JM, Vander Elst L, Muller RN: Dynamic evaluation of the hepatic uptake and clearance of manganese-based MRI contrast agents: a 31P NMR study on the isolated and perfused rat liver. J Magn Reson Imaging. 1998 May-Jun;8(3):663-9. [Article]
8. European Medicines Agency (EMA): TESLASCAN Summary of Product Characteristics [Link]
9. European Medicines Agency (EMA): TESLASCAN Scientific Discussion [Link]

External Links

PubChem Compound

131704299

PubChem Substance

310264892

ChemSpider

32700460

RxNav

236987

Wikipedia

Mangafodipir

Clinical Trials

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Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Cancer / Neurotoxic Disorders	1
2	Completed	Treatment	Chemotherapy / Colon Cancer	1
2	Completed	Treatment	Myocardial Infarction	1
1	Completed	Diagnostic	Multiple Sclerosis	1
1	Not Yet Recruiting	Diagnostic	Epilepsy	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Intravenous	0.01 mmol/ml
Solution	Intravenous	37.9 mg / mL
Injection		0.01 mmol/50ml

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	1.06 mg/mL	ALOGPS
logP	0.79	ALOGPS
logP	-1.8	Chemaxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	1.38	Chemaxon
pKa (Strongest Basic)	-6.4	Chemaxon
Physiological Charge	-4	Chemaxon
Hydrogen Acceptor Count	16	Chemaxon
Hydrogen Donor Count	6	Chemaxon
Polar Surface Area	286.5 Å2	Chemaxon
Rotatable Bond Count	17	Chemaxon
Refractivity	164.24 m3·mol-1	Chemaxon
Polarizability	56.97 Å3	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

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Drug created at September 14, 2010 16:21 / Updated at February 02, 2024 22:53