EARL at a Glance: History, Projects, Visions

30.10.2012 EANM‘12

� EANM founded the EANM Research Ltd in 2006

(Nominal capital of € 35.000)

� EANM is 100% shareholder

� Rationale: Liability

� CEOs

A. Bauer K. Tatsch

History of EARL

EARL at a Glance

EARL was created to unleash the power of molecular imaging and further:� To improve nuclear medicine and its practice within the European Union

� To provide a basis for discussion and the exchange of cutting edge ideas

� To act as a contact point for researchers as well as for clinicians and business leaders

� To provide a platform for the efficient pursuit of scientific initiatives

� To facilitate multicentric research projects

� To enhance the comparability of data acquired by molecular imaging

� To boost molecular imaging so that it becomes a standard diagnostic modality in future clinical medicine and research

� To position nuclear medicine within the EU research agenda

Organisational Structure

EARL

Scientific Advisory Board

ENC-DAT EARL FDG PET/CT Accreditation

WG to review FDG PET guidelines

EPIBTaskforce

EU grants

PEDDOSE.NET

EIBIR Project

MEDRAPET

ESR Project

CEO

K. Tatsch

CEO

A. Bauer

� CEOs report to EANM Executive Committee

� Committees (Networks of Excellence, NoEs)

� ENC-DAT study

2006 – 2010 EARL conducted its first research project:

“European database of [123I] FP-CIT (DaTSCAN) SPECT

scans of healthy controls (ENC-DAT)”.

• 13 centers in 10 European countries

• Multicenter cross-calibration

• Standardized evaluation by core labs

EARL Project

EARL Project

�Rationale ENC-DAT study:

�Overcome limitations

due to:

Lack of standardization• camera performance • acquisition parameters• processing• quantification

Lack of reference data baseof healthy controls• age corrected• gender values

DaTSCAN SPECT:

In clinical practice and clinical trials the quality spectrum of scansranges from excellent to nondiagnostic

� ENC-DAT study part 1: Quality control of imaging device

Gamma camera-certification (1 expert physicist)Initial:

I-123 intrinsic uniformitySystem uniformity with Co-57System sensitivity with I-123Quantitative SPECT resolution with I-123Qualitative resolution planar CORAntropomorphic 3D striatal-phantom

Periodically:System uniformity with Co-57COR

EARL Project

� ENC-DAT study part 2: Phantom measurements

Cross calibration between camera systems

EARL Project

TRUE = 1.0139*measured

R2 = 0.9844

-1

0

1

2

3

4

5

6

7

8

9

10

-1 0 1 2 3 4 5 6 7 8 9 10

Measured SBR (ACSC)

Tru

e S

BR

� ENC-DAT

study:

Equipment

EARL Project

Centre Scanner Collimator

Amsterdam Strickmann N/A

Siemens E-Cam LEHR-PAR

Ankara GE Infinia LEHR-PAR

Copenhagen Philips IRIX LEGP-PAR

Genoa GE Millennium VG LEHR-PAR

Leipzig Uni DSI Ceraspect N/A

Siemens Symbia LEHR-PAR

Leuven Siemens E-Cam LEHR-PAR

Philips IRIX LEUHR-FAN

London GE Infinia Hawkeye LEHR-PAR

Munich Picker Prism3000 LEHR-FAN

Siemens Symbia LEHR-PAR

Nice Picker Prism3000 LEUHR-FAN

Stockholm Trionix TRIAD LEUHR-PAR

Yvoir Trionix TRIAD LEUHR-PAR

Philips IRIX FANB-Asymmetrical

Milan Philips IRIX LEUHR-FAN

Picker Prism LEHR-PAR

Southampton GE Infinia Hawkeye LEHR-PAR

Mediso LEHR-PAR

Vienna GE Millenium LEHR-PAR

Philips IRIX Precision LEHR-PAR

� ENC-DAT study: Recruitment

EARL Project

Age

20-30

30-40

40-50

50-60

60-70

70-80

80-90

Total

Age

yrs male female male female male female male female male female male female male female male female

20-30 1 2 2 3 1 1 1 1 1 1 1 1 1 1

30-40 2 1 2 1 1 1 1 1 1 1 1 1 1

40-50 1 1 1 1 1 1 1 1 1 1 1 1 1 1

50-60 1 1 2 2 1 1 1 1 2 1 1 1 1

60-70 4 3 3 1 1 2 2 2 3 1 1 1 1

70-80 1 1 1 1 2 1 1 2 0 1 1 1 2

80-90 1 0 0 1 1

5 5 5 5 10 6 7 7 7 7 9 7 7 7 5 7

Total 16

Munich Leuven Yvoir Nice

1410 14

Amsterdam

10 16

Ankara GenoaCopenh. R.

1214

Age

20-30

30-40

40-50

50-60

60-70

70-80

80-90

Total

male female male female male female male female male female male female total

1 1 1 1 9 13 22

1 1 1 1 1 1 1 1 14 9 23

2 2 1 1 1 1 13 9 22

1 2 1 1 9 12 21

2 1 3 4 1 1 20 17 37

2 2 1 0 2 1 12 11 23

1 3 1 4

8 7 5 5 7 7 3 0 2 2 80 72

152

Southampton

315

Stockholm

14

London

10

Vienna TotalLeipzig

4

� ENC-DAT study part 3: Healthy subjects

EARL Project

�No history of parkinsonism in first-degree relatives�No medication known to affect DAT binding�UPDRS score: < 60 yrs = 0; ≥ 60 yrs ≤ 5�SCL-90-R score < 63�BDI score ≤ 9�MMSE ≥ 28�Negative urine based screening for drug abuse (10 drugs)�Edinburgh Handedness Test�Copenhagen Smoking Questionnaire�MRI: < 60 yrs ARWMC score 0; > 60 yrs score ≤ 2

� ENC-DAT study part 3: Healthy subjects

EARL Project

y = -0.0566x + 11.897

R2 = 0.4213

y = -0.0531x + 11.471

R2 = 0.3832

2

4

6

8

10

12

14

16

10 20 30 40 50 60 70 80 90

age (years)

SB

R (A

CS

C)

F

My = -0.0547x + 11.668

R2 = 0.3978

2

4

6

8

10

12

14

16

10 20 30 40 50 60 70 80 90

age (years)

SB

R (A

CSC

k=adj)

ALL SBR = -0.0547 * age + 11.668 R2 = 0.398SBR = -0.0566 * age + 11.897 R2 = 0.421

SBR = -0.0531 * age + 11.471 R2 = 0.383

� ENC-DAT study part 3:

Healthy subjects

• World’s largest normal data base of FP-CIT scans

• 152 subjects, 20 to 90 yrs

• Balanced gender

• Intensive neurological/neuropsychiatric evaluations

• MRI scans

• Highly significant relationship between DAT binding and age (decline per decade: 4.6%)

FP-CIT SPECT scans of healthy subjects

EARL Project

� ENC-DAT study outcome

• The normal database established by this project is a valuable

benchmark for Nuclear Medicine centres performing

neuroimaging studies.

• Database was sold to GEHC and HERMES

(further companies have expressed interest).

• Study data are available (online) for scientific projects of

participating sites (n > 10).

• Publications can be found on http://earl.eanm.org

EARL Project

EARL Project

1.Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database. Dickson JC, Tossici-Bolt L, Sera T, de Nijs R, Booij J, Bagnara MC, Seese A, Koulibaly PM, Akdemir UO, Jonsson C, Koole M, Raith M, Lonsdale MN, George J, Zito F, Tatsch K. Eur J Nucl Med Mol Imaging. 2012 Jan;39(1):188-97.

2.Calibration of gamma camera systems for a multicentre European ¹²³I-FP-CIT SPECT normal database. Tossici-Bolt L, Dickson JC, Sera T, de Nijs R, Bagnara MC, Jonsson C, Scheepers E, Zito F, Seese A, Koulibaly PM, Kapucu OL, Koole M, Raith M, George J, Lonsdale MN, Münzing W, Tatsch K, Varrone A. Eur J Nucl Med Mol Imaging. 2011 Aug;38(8):1529-40.

3.European multicentre database of healthy controls for [¹²³I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis. Varrone A, Dickson J, Tossici-Bolt L, Sera T, Asenbaum S, Booij J, Kapucu O, Kluge A, Knudsen GM, Koulibaly PM, Nobili F, Pagani M, Sabri O, Vander Borght T, Van Laere K, Tatsch K. Eur J Nucl Med Mol Imaging. EPUB, DOI: 10.1007/s00259-012-2276-8.

ENC-DAT Publications: Group

EARL Project

1. The impact of reconstruction method on the quantification of DaTSCAN images. Dickson JC, Tossici-Bolt L, Sera T, Erlandsson K, Varrone A, Tatsch K, Hutton BF. Eur J Nucl Med Mol Imaging. 2010;37:23-35

2. No association between striatal dopamine transporter binding and body mass index: A multi-center European study in healthy volunteers. van de Giessen E, Hesse S, Caan MW, Zientek F, Dickson JC, Tossici-Bolt L, Sera T, Asenbaum S, Guignard R, Akdemir UO, Knudsen GM, Nobili F, Pagani M, Vander Borght T, Van Laere K, Varrone A, Tatsch K, Booij J, Sabri O. Neuroimage. 2012 Sep 13;64C:61-67.

3. Automatic semi-quantification of [123I] FP-CIT SPECT scans in healthy volunteers using BASGAN -version 2. Results from the ENC-DAT database. Nobili FN,. Shoustari MN, De Carli F, Asenbaum S, Booij J, Darcourt J, Ell P, Kapucu Ö, Kemp P, Varer C, Morbelli S, Pagani M, Sabri O, Tatsch K, Tossici-Bolt L, Sera T, Vander Borght T, Van Laere K, Varrone A. Eur J Nucl Med Mol Imaging. Accepted, in Press.

4. Value of semi-quantitative analysis for clinical reporting of [123I]FP-CIT SPECT studies. Söderlund TA, Dickson JC, Prvulovich E, Ben-Haim S, Kemp P, Booij J, Nobili F, Thomsen G, Sabri O, Koulibaly PM, Akdemir OU, Pagani M, van Laere K, Asenbaum-Nan S, George J, Sera T, Tatsch K, Bomanji J. JNMMI (accepted with minor revision).

5. Association of serotonin transporter availability and body mass index in healthy Europeans. Hesse S, van de Giessen E, Zientek F, Petroff D, Winter K, Dickson JC, Tossici-Bolt L, Sera T, Asenbaum S, Darcourt J, Akdemir UO, Knudsen GM, Nobili F, Pagani M, Vanderborght T, Van Laere K, Varrone A, Tatsch K, Sabri O, Booij J. Obesity; in review

ENC-DAT Publications: Center-Based Projects

EARL Project

GE-HC: Quantification based on

ENCDAT: DaTQUANT

• DaTSCAN template of healthy controlsfrom ENCDAT

• MNI space

• VOI map (S,C,P,AP,PP)

• Co-registration

• SBR

• P/C

• Asymmetry

EARL Project

Hermes: Quantification

with ENC-DAT BRASS

• DaTSCAN template of healthy controlsfrom ENCDAT

• MNI space

• VOI map

• Co-registration

• SBR

• P/C, PP/AP/C

• Pixelwise comp.

• Age corrected reference values

• Camera specific

� „Calibration of cameras“

EARL offers a service of „calibration of gamma cameras

for ENC-DAT”. An expert physicist comes to calibrate the

equipment in the individual department in the same way as

done for the ENC-DAT project. Thus, the departments’

measurements can easily be compared with the normal

database of the DaTSCAN project.

EARL Service

� Accreditation program

• Quality standard: FDG-PET and PET/CT – EANM procedure

guidelines for tumour PET imaging (version 1.0)

• Online questionnaire

• Quarterly calibration quality control (QC) and annual image

quality QC

• Europe-wide

PET/CT systems are operated quantitatively and have a similar

performance in a multicenter setting.

EARL FDG-PET/CT Accreditation

� EARL: accreditation of imaging sites for EORTC Trial

• EORTC Imaging Group (S. Stroobants)

• Accreditation of 11 sites in D, NL, B, F

• EORTC will only allow accredited imaging centers to

participate in their trials

• MoU between EANM/EORTC:

a) incorporating PET/CT in clinical trials from the very

beginning

b) quality standard

EARL FDG-PET/CT Accreditation

� EARL: accreditation of imaging sites in NM

• First step: EARL asked 60 top imaging centers in Europe to

accredit themselves (EARL charges € 1000.- service fee)

• Second phase: EARL aims at asking all NM departments in

Europe to accredit themselves

• Benefit for the centers: they can join oncological research

projects and sites are published on the EARL/EANM website

as PET/CT accredited sites; certificate; quality label for

machine

EARL FDG-PET/CT Accreditation

�EPIB (European initiative for PET as Imaging Biomarker)

• Inter-Committee working group was set up in 2010

(Representatives of the Oncology, Translational Molecular

Imaging, Radiopharmacy and Drug Development Committees)

• To raise awareness and enforce acceptance and legislation of PET

as Imaging Biomarker

• EU is just beginning to consider the topic „biomarkers“

EARL Project

� Taskforce-EU Grants

• Created in June 2011

• Aim: to raise awareness within the nuclear medicine community of

the necessity of competing for EU research grants as well as

conducting multicentre studies.

• Main objectives:

− To boost the role of molecular imaging in personalised medicine

− To make the European Union (EU) aware of research topics in

nuclear medicine which will be pivotal in the future

− To follow open calls from the EU and the development of recent

grants in order to develop opportunities for nuclear medicine

EARL Project

� EANM is shareholder of EIBIR

(European Institute for Biomedical Imaging Research)

K. Tatsch is official representative of EANM at EIBIR

• PEDDOSE.NET (2010)

„Dosimetry and Health Effects of Diagnostic Applications of

Radiopharmaceuticals with particular emphasis on the use in

children and adolescents.“

EANM - EIBIR

� PEDDOSE.NET (2010) Objectives:

• Summary and evaluation of current knowledge on the impact onpatients' health of small and non- or little-repetitive doses (amounts) ofradioactive, biological and/or chemical substances, as currently usedin diagnostic imaging procedures

• Development of recommendations and guidelines to drive scientificand technologic innovation to improve patient healthcare in med. imaging

• Identification, if clinical studies are needed, and correspondingdetailing of the studies

• Involvement of people in legislative approval of these agents forhuman use

Aim: Development of recommendations and guidelines

EANM - EIBIR

� MEDRAPET (2010)

„Study on the Implementation of the Medical Exposure Directives

Requirements on Radiation Protection Training of Medical

Professionals in the European Union.“

• The results of the 27-months project will form the basis for the revision of the

Radiation Protection 116 Guidelines on Education and Training in Radiation

Protection for Medical Exposures.

• Aim is to provide an improved implementation of the Medical Exposure

Directive provisions related to radiation protection education and training of

medical professionals in the EU Member States.

EANM - EIBIR

� Complementing / implementing EANM vision of “going clinical”

� Extend FDG PET/CT accreditation to NM in whole of Europe

� Raise awareness with “big pharma” / CROs of the importance

of standardization of imaging

� Relevance of multicentre trials for innovative

radiopharmaceuticals

EARL Visions

� What can EARL do for you:

� provide an extensive network of excellent professionals

in the field of nuclear medicine.

� facilitate your clinical (multicentric) study. EARL works

closely together with the principal investigator (PI) as well

as the contract research organization (CRO).

� provide a platform for scientific initiatives.

EARL4you

� What can EARL do your you:

� open to cutting edge ideas – requests for academic/

commercial research projects can be directed to EARL.

� ready to accept project proposals from nuclear medicine

stakeholders, preferentially in the following priority fields:

Cardiology, Drug & Radiopharmaceutical Development,

Neurology/Psychiatry, Oncology, Paediatrics, and

Radionuclide Therapy.

EARL4you

� Create a Win-Win situation by financial support of EARL:

� Associate your Company’s name with the future of molecular imaging

now, and harvest the fruits of your commitment soon, by:

� Increasing the use of molecular imaging in clinical medicine

� Accelerating the development of new radiopharmaceuticals

� Stimulating multicentre drug development and biomedical research

� Ultimately increasing your sales in nuclear medicine

� For discussion of individual models of support or further information

please contact EARL.

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