High Relaxivity AgentsHigh Relaxivity Agents in MR Imaging · High Relaxivity Agents in MR Imaging Emanuel Kanal, MD, FACR, FISMRM 1 For education purposes only. ©2011 ABC ... Omniscan

High Relaxivity Agents in MR ImagingEmanuel Kanal, MD, FACR, FISMRMwww.ImagingEducation.com

1For education purposes only. ©2011 ABC Medical Education LLC.Please do not reproduce without permission.

High Relaxivity AgentsHigh Relaxivity AgentsHigh Relaxivity AgentsHigh Relaxivity Agentsin MR Imagingin MR Imaging

Emanuel Kanal, MD, FACR, FISMRMProfessor of Radiology and NeuroradiologyProfessor of Radiology and Neuroradiology

Department of RadiologyUniversity of Pittsburgh Medical Center

Pittsburgh, Pennsylvania

W dWe can doBETTER!BETTER!



Generic Name Trade NameDate FDA

GBCAs Approved in the United States

Generic Name Trade NameApproved

Gadofosveset trisodium

Gadoxetate disodium

Gadobutrol

Gadopentetate dimeglumine

Gadobenate dimeglumine

Ablavar®/Vasovist®

Eovist®/Primovist®

Gadavist™

Magnevist®

MultiHance®

2008

2008

2011

1988

2004

Gadodiamide

Gadoversetamide

Gadoteridol

Omniscan™

OptiMARK™

ProHance®

1993

1999

1992

GBCAs=gadolinium-based contrast agents.

Generic NameTrade Name

Structure IonicityConc.

(M)Protein Interxn

Clinical Use

Gadofosveset Ablavar/Li I i 0 25 St

Blood

Overview of GBCA Properties

Gadofosvesettrisodium

Ablavar/Vasovist

Linear Ionic 0.25 StrongBlood Pool

Gadoxetatedisodium

Eovist/Primovist Linear Ionic 0.25 Weak Liver

Gadobutrol Gadavist Macrocyclic Nonionic 1.0 None ECF

Gadopentetate dimeglumine

Magnevist Linear Ionic 0.5 None ECF

Gadobenate dimeglumine

MultiHance Linear Ionic 0.5 WeakECF + Liver

Gadodiamide Omniscan Linear Nonionic 0.5 None ECF

Gadoversetamide OptiMARK Linear Nonionic 0.5 None ECF

Gadoteridol ProHance Macrocyclic Nonionic 0.5 None ECF



The Role of r1 (Relaxivity) in T1The Role of r1 (Relaxivity) in T1--weighted MRIweighted MRI

Kanal RelaxivityKanal RelaxivityWebinar 11/1/11Webinar 11/1/11

Unenhanced Contrast enhanced


Unenhanced Low r1 Slightly > r1 Notably > r1




Unenhanced Low r1 Slightly > r1 Notably > r1

It is because of the relaxivity of the contrast agents that we administer them to the patients in the first

l !

MR Contrast Agents: Are They All the Same?MR Contrast Agents: Are They All the Same?

place!

The greater the (r1) relaxivity the brighter the lesion on the T1-weighted image



Comparison of Magnetic Properties of MRI Contrast Media Solutions at Different Magnetic Field Strengthsg g

M. Rohrer, H. Bauer, J. Mintorovitch, M. Requardt, and H.J. Weinmann

Rohrer M et al. Invest Radiol. 2005;40:715-724.

Contrast Agent r1 (mmol-1s-1) r2 (mmol-1s-1)Gadoterate(Dotarem®)

3.6 4.3

Relaxivity of Relaxivity of NeuroNeuro GBCAs (at 1.5T)GBCAs (at 1.5T)

(Dotarem )

Gadopentetate(Magnevist®)

4.1 4.6

Gadoteridol(ProHance®)

4.1 5.0

Gadodiamide(Omniscan™)

4.3 5.2

Gadoversetamide 4 7 5 2Gadoversetamide(OptiMARK™)

4.7 5.2

Gadobutrol(Gadavist™)

5.2 6.1

Gadobenate(MultiHance®)

6.3 8.7

Rohrer M et al. Invest Radiol. 2005;40:715-724.

Very similar r1 and r2 Slightly > r1 and r2 Notably >> r1 and r2



Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist), and ( g ), ( ),

Gadobenate Dimeglumine (MultiHance) in Human Blood Plasma at 0.2, 1.5, and 3 Tesla

J. Pintaske, P. Martirosian, H. Graf, G. Erb, K.P. Lodemann, C.D. Claussen, and F. Schick

Pintaske J et al. Invest Radiol. 2006;41:213-221 [erratum in Invest Radiol. 2006;41:859].

Relaxivity of GBCAs at 1.5TRelaxivity of GBCAs at 1.5T

Contrast Agentr1

(mmol-1s-1)r2

(mmol-1s-1)( ) ( )

Gadopentetate (Magnevist®) 3.9 5.3

Gadobutrol (Gadavist™) 4.7 7.5

Gadobenate (MultiHance®) 7.9 18.9

Notably higher r1 and r2Very similar r1 and r2 Slightly higher r1 and r2




Rohrer Pintaske

Contrast Agent r1 (mmol-1s-1) r2 (mmol-1s-1) r1 (mmol-1s-1) r2 (mmol-1s-1)G d t t

RelaxivityRelaxivity of GBCAs at 1.5Tof GBCAs at 1.5T

Gadoterate(Dotarem®)

3.6 4.3


4.1 4.6 3.9 5.3

Gadoteridol(ProHance®)

4.1 5.0

Gadodiamide(Omniscan™)

4.3 5.2

Gadoversetamide 4 7 5 2Gadoversetamide(OptiMARK™)

4.7 5.2

Gadobutrol(Gadavist™)

5.2 6.1 4.7 7.5


6.3 8.7 7.9 18.9

Why - HOW - are they different?Rohrer M et al. Invest Radiol. 2005;40:715-724.Pintaske J et al. Invest Radiol. 2006;41:213-221 [erratum in Invest Radiol. 2006;41:859].

Comparative Study of the Physicochemical Properties of Six Clinical Low Molecular Weight p g

Gadolinium Contrast Agents

Sophie Laurent , Luce Vander Elst, and Robert N. Muller

Laurent S et al. Contrast Media Mol Imaging. 2006;1:128-137.



15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadopentetate 1(Magnevist)

Proton Lamor Frequency (MHz)

15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadoterate 2(Dotarem)

Proton Lamor Frequency (MHz) • Apparent relaxivity profiles of solutions

15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadodiamide 3(Omniscan)


Gadobenate 5

15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadoteridol 4(ProHance)


profiles of solutions containing 1 mM of the contrast agents and 4% HSA. The lower dashed lines correspond to the theoretical fitting obtained in water and upper solid lines correspond

15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadobenate 5(MultiHance)


15

10

5

0

ˡˡ r1ˡˡ (

s-1 m

M-1

)

0.01 0.1 1 10 100 1000

Gadobutrol 6(Gadavist)

Proton Lamor Frequency (MHz)Adapted from Laurent S et al. Contrast Media Mol Imaging. 2006;1:128-137.

pto the expected profiles when the effects of the viscosity increase on τR and D are taken into account.

0.5T-1.5T

Adapted from Laurent S et al. Contrast Media Mol Imaging. 2006;1:128-137.



MR Contrast Agents: Are They All the Same?MR Contrast Agents: Are They All the Same?

MultiHance is the only GBCA clinically approved/used for neuroradiologic imagingapproved/used for neuroradiologic imaging that weakly binds to proteins. This directly results in marked increases in relaxivity and shortening of tissue T1 values, yielding noticeably more intense signal on T1-weighted images.

Influence of Human Serum Albumin on Longitudinal and Transverse Relaxation Rates (r1 and r2) of ( )

Magnetic Resonance Contrast Agents

F.L. Giesel, H. von Tengg-Kobligk, I.D. Wilkinson, P. Siegler, C.W. von der Lieth, M. Frank, K.P. Lodemann, and M. Essig

Giesel FL et al. Invest Radiol. 2006;41:222-228.



R1 Relaxation RatesR1 Relaxation Rates

7 g/dL HSA

0 g/dL HSA3.5 g/dL HSA

5.5 g/dL HSA

/se

c]

/P t i

12

10

12

10/se

c] Gd-DTPA

Gd-BOPTAGd-BT-DO3A

12

10/se

c]

(A) (B) (C)

Re

lax

ati

on

Ra

te R

1 [

1/

w/o Protein

w/Protein10

8

6

4

2

0

10

8

6

4

2

0R

ela

xati

on

Ra

te R

1 [

1/

1 2 3 4 5 6 7HSA (g/dL)

PhysiologicalRange

Gd BT DO3A 10

8

6

4

2

0

Re

lax

ati

on

Ra

te R

1 [

1/

Adapted from Giesel FL et al. Invest Radiol. 2006;41:222-228.

• Relaxation rate R1 of the different contrast agents Gd-DTPA, Gd-BT-DO3A, and Gd-BOPTA vs HSA concentration. The differences in R1 between the 3 contrast agents are shown separately for the normal range (left panel) and the abnormal range (right panel). The percentage changes between different R1 concentration of each contrast agent is calculated by the equation: Rx %HSA > HSA = [(Rx HSAy/Rx HSAz) × 100] – 100. x = relaxation rate R1 [1/s]; y, z = HSA concentration [g/dL].

20Reprinted with limited permission, courtesy of E. Kanal, MD.



SI vs [GD]; 1.5T TR250 TE14

1000

1200

Normal human steady state T1-weighted imaging

♦ Gadopentetate(M i t)

200

400

600

800 MagnevistMultihanceOmniscanOptimarkProhance

(Magnevist)

× Gadobenate(MultiHance)

■ Gadodiamide(Omniscan)

▲ Gadoversetamide(OptiMARK)

× Gadoteridol(ProHance)

0

200

0 1000 2000 3000 4000 5000

Dilution

Reprinted with limited permission, courtesy of E. Kanal, MD.

SE; TR250, TE 14;[Gd] 1:2048

1000

1200

♦ G d t t t

400

600

800 MagnevistMultihanceOmniscanOptimarkProhance

♦ Gadopentetate(Magnevist)

♦ Gadobenate(MultiHance)

♦ Gadodiamide(Omniscan)

♦ Gadoversetamide(OptiMARK)

♦ Gadoteridol(ProHance)

0

200

0 1 2 3 4

Field Strength

Reprinted with limited permission, courtesy of E. Kanal, MD.

(ProHance)



Extracellular fluid agent A 0.1 mmol/kg

Gadobenate dimeglumine g(MultiHance®)

0.1 mmol/kg

Reproduced with permission from Rowley HA et al. AJNR Am J Neuroradiol. 2008;29:1684-1691.

SE GRE

Conventional Gdcontrast agent


Reproduced with permission from Rowley HA et al. AJNR Am J Neuroradiol. 2008;29:1684-1691.



Primary Primary IntraaxialIntraaxial GliomaGlioma

Conventional Gdcontrast agent


Colosimo C et al. Neuroradiology 2004;46:655-665.

Gadobenate (MultiHance®)

Intraindividual Crossover ComparisonIntraindividual Crossover ComparisonGadopentetateGadopentetate vsvs Gadobenate: Gadobenate: TimecourseTimecourse

0-2 min 2-4 min 4-6 min 6-8 min 8-10 min

Gadopentetate (Magnevist®)Reprinted from Applied Radiology, 2003, April (Suppl). M. Essig et al. Comparison of Gd-BOPTA and Gd-DTPA for contrast-enhanced MRI of intra-axial cerebral brain tumors: a two-center, double-blind randomized intra-individual cross-over study, Pages 92-100, ©2003, with permissionfrom Anderson Publishing Ltd.



Gadopentetate(Magnevist®)0.1 mmol/kg

Gadobenate(MultiHance®) 0.1 mmol/kg

Reproduced with permission from Kuhn MJ et al. J Neurosurg. 2007;106:557-566.



Maravilla KR et al. Radiology. 2006;240:389-400.





Kuhn MJ et al. J Neurosurg. 2007;106:557-566.

Reproduced with permission from Maravilla KR et al. Radiology. 2006;240:389-400. ©2006 RSNA.







Images courtesy of K. Maravilla, MD.



Kuhn MJ et al. J Neurosurg. 2007;106:557-566.





Reproduced with permission from Maravilla KR et al. Radiology. 2006;240:389-400. ©2006 RSNA.



Images courtesy of K. Maravilla, MD.



Gadobenate dimeglumine (MultiHance®)

Conventional GdContrast Agent

Images courtesy of A. Tartaro, MD.

1.5T system20 degrees3DFT

Patient with Metastases Patient with Metastases

3DFTDouble doseGadoversetamide (OptiMARK™)TR 21TE 6

Image courtesy of E. Kanal, MD.



1.5T system20 degrees3DFT

Patient with Metastases Patient with Metastases

3DFTDouble doseGadobenate(Multihance®)TR 21TE 6

Image courtesy of E. Kanal, MD.

Prospective Comparison of Image Quality and Diagnostic Accuracy of 0.5M Gadobenate Dimeglumine and 1.0M y g

Gadobutrol in CE Run-Off MRA of the Lower Extremities

Marina Achenbach, Jens H. Figiel, Mykhaylo Burbelko,and Johannes T. Heverhagen

Achenbach M et al. J Magn Reson Imaging. 2010;32:1166-1171.



Evaluable Segments, Detected Stenoses, Evaluable Segments, Detected Stenoses, Image Quality, and Venous ContaminationImage Quality, and Venous Contamination

GadobutrolInvestigator 1 Investigator 2

GadobenateInvestigator 1 Investigator 2

Nonevaluable (evaluable) segments

33 (818) 47 (804) 18 (833) 25 (826)

Clinically relevant stenoses d i t d (%)

21.0 (172/818) 24.9 (200/804) 20.5 (171/833) 23.1 (191/826)depicted (%)

21.0 (172/818) 24.9 (200/804) 20.5 (171/833) 23.1 (191/826)

kappa 0.54 0.53

Median image quality 1 1 1 1

kappa 0.52 0.53

Median venous contamination

1 0 1 0

Achenbach M et al. J Magn Reson Imaging. 2010;32:1166-1171.

Investigator 1 found no statistically significant differences between both groups (P = 0.61) and Investigator 2 found the image quality significantly better in the gadobenate group in comparison to the gadobutrol group (P = 0.01)

Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine p g

and Gadopentetate Dimeglumine for MR Angiography of Peripheral Arteries

S.C. Gerretsen, T.F. le Maire, S. Miller, S.A. Thurnher, C.U. Herborn, H.J. Michaely, H. Kramer, A. Vanzulli, J. Vymazal, M.N. Wasser,

C.E.M. Ballarati, M.A. Kirchin, G. Pirovano, and T. Leiner

Gerretsen SC et al. Radiology. 2010;255:988-1000.



Reprinted with permission from Gerretsen SC et al. Radiology. 2010;255:988-1000. ©2010 RSNA.







ConclusionConclusion

Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0 1 mmol/kg doses in patients undergoingcompared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease

Gerretsen SC et al. Radiology. 2010;255:988-1000.



Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine andCrossover Comparison of Gadobenate Dimeglumine and

Gadopentetate Dimeglumine for Breast MR Imaging (DETECT Trial)

L. Martincich, M. Faivre-Pierret, C.M. Zechmann, S. Corcione, H.C. van den Bosch, W.J. Peng, A. Petrillo, K.C. Siegmann,

J.T. Heverhagen, P. Panizza, H.B. Gehl, F. Diekmann, F. Pediconi, L. Ma, F.J. Gilbert, F. Sardanelli, P. Belli, M. Salvatore, K.F. Kreitner,

C M W i d C Z i iC.M. Weiss, and C. Zuiani

Martincich L et al. Radiology. 2011;258:396-408.

DETECT Study (February DETECT Study (February 20112011))

Gadobenate (MultiHance®) vsGadopentetate (Magnevist®)Gadopentetate (Magnevist )Multicenter, double-blind crossover study 0.1 mmol/kg gadobenate (MultiHance) 0.1 mmol/kg gadopentetate (Magnevist)Endpoints

B t d t ti t– Breast cancer detection rate– Diagnostic performance for lesion detection– Characterization by region (10/patient)




DETECT Study (February 2011)DETECT Study (February 2011)

Gadobenate (MultiHance®) vsGadopentetate (Magnevist®)Gadopentetate (Magnevist ) July 2007 through May 2009 82 received gadobenate (MultiHance) first,

gadopentetate (Magnevist) second 80 received gadopentetate (Magnevist) first,

gadobenate (MultiHance) secondgadobenate (MultiHance) second 151 subjects underwent both studies

(2 days < MR exam < 7 days)


Reader 1 Reader 2 Reader 3

144 Malignant Lesions144 Malignant Lesions

DETECT Study (DETECT Study (February 2011February 2011))

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Cancer

detection rate91.7% 79.9% 93.1% 80.6% 94.4% 83.3%

P value

(McNemar’s test)

< 0.0001 < 0.0001 0.0003

False-positive 5 8% 5 8% 9 8% 7 3% 12 6% 23 2%rate 5.8% 5.8% 9.8% 7.3% 12.6% 23.2%

Cancer misdiagnosed (FN)

12 29 10 28 8 24

FN=false-negative findings.







Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Cancer

detection rate91.7% 79.9% 93.1% 80.6% 94.4% 83.3%

P value

(McNemar’s test)

< 0.0001 < 0.0001 0.0003



12 29 10 28 8 24




DETECT Study (February DETECT Study (February 20112011))

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Cancer

detection rate91.7% 79.9% 93.1% 80.6% 94.4% 83.3%

P value

(McNemar’s test)

< 0.0001 < 0.0001 0.0003



12 29 10 28 8 24







Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Gadobenate

(MultiHance)

Gadopentetate

(Magnevist)

Cancer

detection rate91.7% 79.9% 93.1% 80.6% 94.4% 83.3%

P value

(McNemar’s test)

< 0.0001 < 0.0001 0.0003



12 29 10 28 8 24


Reader 1 Reader 2 Reader 3Gadobenate Gadopentetate Gadobenate Gadopentetate Gadobenate Gadopentetate

1450 Regions1450 Regions


(MultiHance) (Magnevist) (MultiHance) (Magnevist) (MultiHance) (Magnevist)

Sensitivity 91.1% 81.2% 94.5% 82.6% 95.2% 84.6%

P value = 0.0005 < 0.0001 = 0.0011

Specificity 99% 97.8% 98.2% 96.9% 96.9% 93.8%

P value = 0.006 = 0.0094 = 0.0001

PPV 91.1% 80.7% 85.2% 75.5% 77.2% 60.9%

P l < 0 0001 0 0002 < 0 0001P value < 0.0001 = 0.0002 < 0.0001

NPV 99% 97.8% 99.4% 98% 99.4% 98.1%

P value < 0.0001 < 0.0001 = 0.0003

Accuracy 98.2% 96.1% 97.8% 95.4% 96.7% 92.8%

P value < 0.0001 < 0.0001 < 0.0001NPV=negative predictive value; PPV=positive predictive value.





High Grade Ductal Carcinoma In SituHigh Grade Ductal Carcinoma In Situ

Gadobenate(MultiHance®)( )

Images courtesy of L. Martincich, MD.

Maximum Intensity ProjectionsMaximum Intensity Projections



Reprinted with permission from Martincich L et al. Radiology. 2011;258:396-408. ©2011 RSNA.



MammographyGadobenate

(MultiHance)*Gadopentetate (Magnevist)*

122 Lesions122 Lesions

Comparison Comparison vsvs Mammography (109 patients)Mammography (109 patients)

(MultiHance) (Magnevist)

Cancers detected 95 115–117 99–104

Cancer detection rate 78% 94%–96% 81%–85%

Mammography vs. gadobenate (MultiHance)P < 0.001

(all 3 readers)

P 0 05

*Range from 3 readers.

Gilbert FJ et al. Presented at ECR 2011; March 3-7, 2011 [poster].

Mammography vs. gadopentetate (Magnevist)P > 0.05

(all 3 readers)

Gadobenate (MultiHance) vs. gadopentetate (Magnevist)

P < 0.001

(all 3 readers)

Comparison Comparison vsvs Ultrasound (114 patients)Ultrasound (114 patients)

UltrasoundGadobenate

(MultiHance)*Gadopentetate (Magnevist) *

123 Lesions123 Lesions

(MultiHance) (Magnevist)

Cancers detected 89 112–116 95–101

Cancer detection rate 72% 91%–94% 77%–82%

Ultrasound vs. gadobenate (MultiHance)P < 0.001

(all 3 readers)

*Range from 3 readers.

Ultrasound vs. gadopentetate (Magnevist)P > 0.05 (2 readers)P = 0.046 (1 reader)

Gadobenate (MultiHance) vs. gadopentetate (Magnevist)

P < 0.001

(all 3 readers)

Gilbert FJ et al. Presented at ECR 2011; March 3-7, 2011 [poster].



DETECT Study (DETECT Study (February February 20112011))

Adverse Events (AEs)Gadobenate (MultiHance)

Gadopentetate (Magnevist)( ) ( g )

Subjects with AEs 8 (5.1%) 11 (7.1%)

Mild 8 (5.1%) 11 (7.1%)

Moderate 0 0


Severe 0 0

Subjects with related AEs 6 (3.7%) 7 (4.3%)

ConclusionConclusion

Gadobenate dimeglumine is superior togadopentetate dimeglumine for breast

di icancer diagnosis




How do gadobutrol (Gadavist™) and gadobenate (MultiHance®) compare?

Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadavist), and Gadobenate Gadobu o (Gada s ), a d Gadobe a e

Dimeglumine (MultiHance) in Human Blood Plasma at 0.2, 1.5, and 3 Tesla

J. Pintaske, P. Martirosian, H. Graf, G. Erb, K. P. Lodemann, C.D. Claussen, and F. Schick




8

10

Gd-DTPA (gadopentetate [Magnevist])

Gd-BOPTA (gadobenate [MultiHance])

Gd-BT-DO3A (gadobutrol [Gadavist])

1.5 Tesla

4

6

R1

[1/s

]

0

2

0.2

Concentration [mM]

0 0.4 0.6 0.8 1.0


1.5 Tesla

1500

1000



Sl [

a, U

,]

500

0

-500

-1000Gd-DTPA (gadopentetate [Magnevist])

T1 [ms]

0

-1500

500 1000 1500 2000

FIT




2000


Gd-DTPA (gadopentetate [Magnevist])


Sl [

a, U

,]

1500

500

FIT

1000

TE [ms]

00

100 200 300 400


7

8

9 1.5 T

3.0 T

Pla

sma

at

37°C

2

3

4

5

6

vity

L/m

mo

l/se

c p

H7

in

P

0

1

Gadopentetate Gadobutrol Gadobenate(Gadavist™)(Magnevist®) (MultiHance®)

r 1R

elax

iv




Food and Drug Administration. Available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM240357.pdf.

Food and Drug Administration. Available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM240357.pdf.



MERIT Study: DesignMERIT Study: Design

Multicenter, double-blind, randomized, intra-individual, crossover study

123 patients at 12 centers referred for 1 5T contrast enhanced 123 patients at 12 centers referred for 1.5T contrast-enhanced MRI for known or suspected brain tumors

Received equivalent gadolinium doses of 0.1 mmol/kg gadobenate (MultiHance®) 0.5M and gadobutrol (Gadavist™) 1.0M in random order

Seidl U et al. AJNR Am J Neuroradiol. 2011 [accepted for publication].

Significant increases in CNR and LBR noted by all 3 readers for gadobenate dimeglumine versus gadobutrol

Quantitative ResultsQuantitative Results

ast-

to-N

ois

e R

atio

60

90

120

150

Gadobutrol Gadobenate dimeglumine

+43.6%

+72.3%+73.0%

to-B

ackg

rou

nd

Rat

io

0.7

0.8

0.9

1.0

Gadobutrol Gadobenate dimeglumine

+22.0% +21.4%+25.0%


P < 0.0001; all 3 readers.P < 0.0186, reader 1; P < 0.0001, reader 2; P = 0.0007, reader 3.

Co

ntr

a

0

30


Les

ion

-t

0.5

0.6




58-year-old FemaleMelanoma met

Gadobutrol(Gadavist™)0.1 mmol/kg

Gadobenate(MultiHance®)0.1 mmol/kg

Images courtesy of Zdenek Seidl, Neurologicka Klinika, Prague, Czech Republic.

58-year-old FemaleMelanoma met

Images courtesy of Zdenek Seidl, Neurologicka Klinika, Prague, Czech Republic.

Gadobutrol(Gadavist™)0.1 mmol/kg

Gadobenate(MultiHance®)0.1 mmol/kg



No benefit of gadobutrol for lesion conspicuity, visualization or sensitivity for detection vs

MERIT Study: MERIT Study: Summary and ConclusionsSummary and Conclusions

visualization, or sensitivity for detection vsgadobenate at equivalent doses– Contrast agent concentration does not impact imaging

performance

Gadobenate provides significantly improved contrast enhancement of brain tumors, both quantitatively and qualitativelyquantitatively and qualitatively– P < 0.05 for all endpoints

No clinically meaningful differences in terms of safety noted between the 2 agents


GadobutrolGadobutrol ((GadavistGadavist™)™) 1 0M1 0MGadobutrolGadobutrol ((GadavistGadavist ) ) 1.0M1.0MGadobenate (Gadobenate (MultiHanceMultiHance®®) 0.5M) 0.5M



Total Patient Gadolinium LoadTotal Patient Gadolinium Load

Half volume gadobutrol (Gadavist™) is the same Gd dose as full volume gadopentetate (Magnevist®) or gadobenate (MultiHance®) or gadodiamide (Omniscan™) or gadoversetamide (OptiMARK™) or gadoteridol (ProHance®)

Half volume can be advantageous for perfusion-weighted imaging



Half volume can be disadvantageous for contrast-enhanced MRA

(less forgiving of timing errors)

ConclusionsConclusions

Relaxivity depends on conditions of measurement

– Field strength

Gadolinium (Gd) concentration– Gadolinium (Gd) concentration

– Presence of protein

– Ultimate proof of differences in relaxivity is the differences in your images

Relaxivity vs concentration

– Higher relaxivity

I i l f i t ti ith t i Increase signal from interaction with serum proteins

– Higher concentration (1.0M)

More Gd per milliliter compared with 0.5M agents

Compared with higher-relaxivity agents, produces weaker enhancement at same Gd dose



ConclusionsConclusions

Don’t confuse volume and dose!

A higher-relaxivity agent consistently demonstrates better diagnostic performance vs lower relaxivity agents at thediagnostic performance vs lower relaxivity agents at the same administered dose

Documents

High Relaxivity AgentsHigh Relaxivity Agents in MR Imaging · High Relaxivity Agents in MR Imaging Emanuel Kanal, MD, FACR, FISMRM 1 For education purposes only. ©2011 ABC ... Omniscan