Prés Molecular Imaging

New developments in

Molecular Imaging

Osman Ratib, MD, PhD

Division of Nuclear Medicine and Molecular Imaging

Department of Medical Imaging and Information Sciences

University Hospital of Geneva

Applications in personalized medicine

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Image 1

Healthcare economics

Shift of paradigm

Keynote Lecture

Elias Zerhouni

International Society

for Strategic Studies

in Radiology

Transformation of medical paradigm

• Treat disease before it becomes symptomatic

•Four P

•Predictive

•Personalized

•Preemptive

•Participatory

• We should better understand how the

molecules we are giving to the patients really

work (how cancer mutate, response,

environment etc..)

•Genomics, proteomics

•Molecular Imaging (quantitative…)

•Radiomics

Molecular Imaging

Evolution of medical imaging

HISTORY

Evolution of molecular imaging

Master Physique Médicale Lyon - Tomographie d’émission monophotonique - Irène Buvat – septembre 2011 - 26

•  Détecteur à scintillations

1951 : scintigraphe à balayage

spectromètre

cristal

imprimante

collimateur

PM

asservissement

mécanique

➩ scintigraphie

1958

Planar scintigram

2015

Hybrid PET-CT

Evolution of medical imaging

3D 4D

Multidetector scanners

Anatomy (CT) Metabolism (PET)

Molecular Imaging

The fifth dimension

Positron emission tomography

Molecular imaging

CT PET

PET vs CT

Pre treatment

Post treatment

Advantages

1994

1998

University of Pittsburgh

Medical Center

Positron Emission Tomography

Invention of hybrid PET-CT

Evolution of hybrid Imaging

PET-CT scanners

PET-CT

T.M. 3487591

Staging in oncology

Better characterization of lesions

PET-CT

T.M. 3487591

Treatment monitoring

Follow up of treatment response

Staging

Post therapy

Mobile PET-CT

Hybrid imaging

From PET-CT to PET-MR

CT PET

CT

PET-CT

PET-MRI

PET-CT

PET

MRI

PET-MRI

Hybrid PET-MRI

Evolution...

PET MRI

Separate

Hybrid PET-MRI

Evolution...

PET MRI

Separate ➟ Co-planar

Hybrid PET-MRI

Evolution...

PET

MRI

Separate ➟ Co-planar ➟ Integrated

PET-MR

hybrid imaging

World premier in hybrid imaging...

Hybrid whole-body PET-MRI

Co-planar registration of standard scanners

MRI

PET

3m

Hybrid PET-MR

• Le PET-CT est un nouvel outil diagnostic pour la détection et

le suivi des cancers

• L’acquisition simultanée de CT et de PET offre des avantages

de qualité diagnostique et de confort pour le patient

• Le PET offre aussi des applications en neurologie, cardiologie

et dans la détection des infections et des foyers

inflammatoires

• Le développement de nouveaux traceurs plus spécifiques

ouvre de nouvelles perspectives dans le diagnostique

précoce des tumeurs et dans l’étude des maladies

neurodégénératives et cardiovasculaires

Clinical applications of hybrid PET-MR

Hybrid PET-MR

Head & Neck

PET$CT

Breast

Prostate

Sarcoma

Pelvis

Clinical applications of hybrid PET-MR

from diagnostic to

Theranostic

A new paradigm in molecular imaging...

THERANOSTICS FOR PERSONALIZED

MOLECULAR TARGETED THERAPY

Shift of paradigm

Theranostics

• Theranostics is the combination of a Diagnostic Tool that also

provides a Therapeutic Tool for a specific disease.

• The right treatment, not anymore targeting the “specific disease”

but the “specific disease expression of a given patient”.

•The right treatment, for the right patient, at the right time, at the

right dose. – first time

• The concept of PM has been extended to Personalized Health Care

that includes all steps from the first sign of disease up to full

recovery

Personalized Medicine

HISTORY

Radionuclide can cure cancer..

Published: !

May 12th 1921

Targeted Radionuclide Therapy

Radium-223 (Alpharadin)

1921

2015

Targeted Radionuclide Therapy

•223Ra (Alpharadin) for treatment of bone metastases in

patients with prostate cancer resistant to hormonotherapy

Radium-223 (Alpharadin)

Targeted Radionuclide Therapy

Radium-223 (Alpharadin)

Targeted Radionuclide Therapy

• Phase II and phase III studies showed

increase in overall survival rate of 3.5

months

• Increase in time to first skeletal-related

event of 5.5 months

Radium-223 (Alpharadin)

Nilsson et al. Lancet Oncol 2007

HISTORY

Theranostics in nuclear medicine

EDITORIAL

Nothing new under the nuclear sun: towards 80 years

of theranostics in nuclear medicine

Frederik A. Verburg

&

Alexander Heinzel

&

Heribert Hänscheid

&

Felix M. Mottaghy

&

Markus Luster

&

Luca Giovanella

Published online: 6 November 2013

#Springer-Verlag Berlin Heidelberg 2013

Some time in the early 2000s, the word “theranostics”(or

“theragnostics”) started surfacing in the medical literature.

Theranostics (from the Greek therapeuein “to treat medically”

and gnosis “knowledge”) is the use of individual patient-level

biologicalinformation in choosing the optimal therapy for that

individual [1]. In the modern era of “personalized medicine”,

theranostics is increasingly pursued in many branches of

medicine in order to develop ever more effective treatment

regimens. There are now many studies and reviews dedicated

to theranostics, and even a journal bearing the name of this

principle, detailing many different concepts on how to

combine imaging and therapy using, for example, complex

molecules [2] or nanotechnology [3].

However, it is rarely realized by either clinicians or scientists

that nuclear medicine has been employing theranostics for

nearly 80 years now. In fact, the very foundations of targeted

therapy in nuclear medicine are those that are only now being

adopted by other medical disciplines under the designation

“theranostics”.

The cornerstones of theranostics can be traced back to some

of the most illustrious names among the founding fathers of

nuclear medicine. Soon after Chiewitz and de Hevesy [4]

described the uptake of radioactive

32

Pinthebonesofrats,Erf

and J.H. Lawrence (brother of the physicist Ernest O. Lawrence,

who built the first cyclotron) applied this same radioisotope to

patients suffering from leukaemia and polycythaemia vera [5].

Although this treatment certainlywasnotwithoutsuccess,ithas

since been superseded by more effective nonradioactive

chemotherapy. Shortly afterwards Pecher [6]discoveredthat

89

Sr accumulated in secondary bone tumours in animals, and

subsequently successfully used this radioisotope to treat patients

with painful bone metastases (unfortunately this work was

immediately classified as secret and it took more than five

decades for

89

Sr to be registered as a therapeutic drug). These

two studies are perhaps the earliest examples of diagnostic

studies leading to targeted therapy of cancer using radionuclides.

Around the same time the most prominent example of pure

nuclear theranostic medicine emerged: the diagnosis and

treatment of thyroid disorders using various isotopes of iodine.

Hertz et al. in 1938 described the first study of thyroidal

radioiodine uptake [7], and in 1942 Hertz and Roberts reported

on the treatment of the first patients with Graves’disease with

radioiodine [8]. A short time later Seidlin et al. treated the first

patient with metastatic thyroid cancer with radioiodine [9]–at

the time this compound was so rare that radioiodine was purified

from the patient’surineandreadministered.Duringthistherapy,

additional metastases were identified using a Geiger counter and

the first rudimentary dosimetry was performed. It is of course

only with the benefit of hindsight that we can now say that this

was the first application of theranostics in targeted molecular

medicine through a specific molecular target, the sodium iodine

symporter, long before any of these concepts were first

described as “theranostics”.Indeed,eventodayitishardto

think of a single combination of targeted diagnostics and therapy

that is more specific than radioiodine.

F. A. Verburg (*)

:

A. Heinzel

:

F. M. Mottaghy

Department of Nuclear Medicine, RWTH University Hospital

Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

e-mail: fverburg@ukaachen.de

F. A. Verburg

:

F. M. Mottaghy

Department of Nuclear Medicine, Maastricht University Medical

Center, Maastricht, The Netherlands

H. Hänscheid

Department of Nuclear Medicine, University of Wuerzburg,

Wuerzburg, Germany

M. Luster

Department of Nuclear Medicine, University Hospitals

Giessen-Marburg, Marburg, Germany

L. Giovanella

Department of Nuclear Medicine, Oncology Institute of Southern

Switzerland, Bellinzona, Switzerland

Eur J Nucl Med Mol Imaging (2014) 41:199–201

DOI 10.1007/s00259-013-2609-2

Radionuclide therapy

• Well established since the 1950s

• Beta and gamma rays

• Self-targeting

131I Therapy for thyroid cancer

Radionuclide therapy

Choice of carriers

Radionuclide therapy

• Monoclonal antibody

• Labelled with Beta emitting isotope

131I/90Y labelled antibody for NHL therapy

CD20

Rituximab

Radionuclide therapy

Treatment of indolent lymphoma with 131I-tositumomab

British Journal of Cancer (2006) 94, 1770 – 1776 et J Nucl Med 2011; 52:896–900F. Buchegger et al

131I/90Y labelled antibody for NHL therapy

Radionuclide therapy

Radio-immunotherapy 90Y-Ibritumomab (Zavalin®)

4

Anticorps monoclonal

(ibritumomab),

associé à un radioisotope

(yttrium-90)

Cellule B

(cellule cancéreuse)

antigène CD20

L’yttrium-90 se décompose en

zirconium-90 stable, par

l’émission des particules bêta

riches en énergie (demi-vie:

2.67 jours).

La portée des rayons bêta de

l’yttrium-90 dans le tissu est de

5 mm au maximum.

Peptide Receptor Radiotherapy (PRRT)

•177LU emits intermediate energy beta

particles (133 KeV)

• Beneficial in small sized tumors (tissue

range 2mm)

• Concomitant gamma emission enables

imaging with gamma cameras

68GA/177LU DOTATOC in Neuroendocrine tumors (NET)

68GA

177LU

68Ga Generators and labeling kits

PET tracers without a cyclotron

Radionuclide therapy

• Phase II results in progressive midgut

carcinoid showed Progression-Free

Survival of more than 44 months

compared to the reported 14.6 months of

Novartis' Sandostatin® LAR

• Lutathera® was shown to increase overall

survival by between 3.5 and 6 years in

comparison to current treatments,

including chemotherapy.

• It was also shown to significantly improve

quality of life

Peptide Receptor Radionuclide Therapy (PRRT)

Lutathera®

Radionuclide therapy

• Phase II results in progressive midgut

carcinoid showed Progression-Free

Survival of more than 44 months

compared to the reported 14.6 months of

Novartis' Sandostatin® LAR

• Lutathera® was shown to increase overall

survival by between 3.5 and 6 years in

comparison to current treatments,

including chemotherapy.

• It was also shown to significantly improve

quality of life

Peptide Receptor Radionuclide Therapy (PRRT)

Lutathera®

PSMA ligand

• PSMA (Prostate Specific Membrane

Antigen) is a membrane glycoprotein

which is overexpressed on prostate

cancers

• PSMA expression increases with tumor

aggressiveness, androgen-

independence, metastatic disease,

and disease recurrence.

• Ga-68 PSMA PET/CT Imaging

identifies tumor cells expressing PSMA

antigen with excellent sensitivity &

specificity.

Prostate-Specific Membrane Antigen

68Ga labelled PSMA ligand

• Type II membrane bound glycoprotein

• Expressed in all forms of prostate tissue

• Over-expressed in carcinoma

• Also found in the neovasculature of most

solid tumors

Prostate-Specific Membrane Antigen

6

7

8

9

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