Theranostics and Image Guided Drug Delivery

253 Pages·2018·12.806 MB·English

by  Maya Thanou, Maya Thanou, David Thurston, Dana Gourevich, Khuloud Al-Jamal, Wady Gedroyc, Sandy Cochran, Rafael T. M. de Rosales, Evren Kemal, Santi Nonell, Lars Lindner, Nan Li

Theranostics and Image Guided Drug Delivery
1
0
0
P
F
7-
9
5
0
1
0
8
8
7
1
8
7
9
9/
3
0
1
0.
1
oi:
d
g |
or
c.
s
s.r
b
u
p
p://
htt
n
o
8
1
0
2
y
ar
u
n
a
J
2
. n 0
o
d
e
h
s
bli
u
P
View Online
Drug Discovery Series
Editor-in-chief:
David Thurston, King’s College, UK
1
0
0
P Series editors:
F
7- David Fox, Vulpine Science and Learning, UK
9
5
0 Ana Martinez, Centro de Investigaciones Biologicas-CSIC, Spain
1
0
8 David Rotella, Montclair State University, USA
8
7
1
8
7
9/9 Editorial advisor:
3
0 Hong Shen, Roche Innovation Center Shanghai, China
1
0.
1
doi: Titles in the Series:
g | 1: Metabolism, Pharmacokinetics and Toxicity of Functional Groups
or
c. 2: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 1
s
bs.r 3: Emerging Drugs and Targets for Alzheimer’s Disease; Volume 2
u
http://p 45:: ANcecwo uFnrotsn tiine rDsr iung C Dhiesmcoivcearly Biology
n 6: Animal Models for Neurodegenerative Disease
o
18 7: Neurodegeneration
0
y 2 8: G Protein-Coupled Receptors
uar 9: Pharmaceutical Process Development
n
Ja 10: Extracellular and Intracellular Signaling
2
. n 0 11: New Synthetic Technologies in Medicinal Chemistry
o
d 12: New Horizons in Predictive Toxicology
e
sh 13: Drug Design Strategies: Quantitative Approaches
ubli 14: Neglected Diseases and Drug Discovery
P
15: Biomedical Imaging
16: Pharmaceutical Salts and Cocrystals
17: Polyamine Drug Discovery
18: Proteinases as Drug Targets
19: Kinase Drug Discovery
20: Drug Design Strategies: Computational Techniques and Applications
View Online
21: Designing Multi-Target Drugs
22: Nanostructured Biomaterials for Overcoming Biological Barriers
23: Physico-Chemical and Computational Approaches to Drug Discovery
24: Biomarkers for Traumatic Brain Injury
1 25: Drug Discovery from Natural Products
0
P0 26: Anti-Inflammatory Drug Discovery
F
7- 27: New Therapeutic Strategies for Type 2 Diabetes: Small Molecules
9
05 28: Drug Discovery for Psychiatric Disorders
1
80 29: Organic Chemistry of Drug Degradation
8
17 30: Computational Approaches to Nuclear Receptors
8
97 31: Traditional Chinese Medicine
9/
3 32: Successful Strategies for the Discovery of Antiviral Drugs
0
1
0. 33: Comprehensive Biomarker Discovery and Validation for Clinical
1
oi: Application
d
g | 34: Emerging Drugs and Targets for Parkinson's Disease
c.or 35: Pain Therapeutics; Current and Future Treatment Paradigms
s
s.r 36: Biotherapeutics: Recent Developments using Chemical and Molecular
b
u Biology
p
p:// 37: Inhibitors of Molecular Chaperones as Therapeutic Agents
n htt 38: Orphan Drugs and Rare Diseases
o
8 39: Ion Channel Drug Discovery
1
20 40: Macrocycles in Drug Discovery
y
ar 41: Human-based Systems for Translational Research
u
an 42: Venoms to Drugs: Venom as a Source for the Development of Human
J
2 Therapeutics
. on 0 43: Carbohydrates in Drug Design and Discovery
d
he 44: Drug Discovery for Schizophrenia
s
bli 45: Cardiovascular and Metabolic Disease: Scientific Discoveries and
u
P New Therapies
46: Green Chemistry Strategies for Drug Discovery
47: Fragment-Based Drug Discovery
48: Epigenetics for Drug Discovery
49: New Horizons in Predictive Drug Metabolism and Pharmacokinetics
50: Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis,
Evaluation
View Online
51: Nanomedicines: Design, Delivery and Detection
52: Synthetic Methods in Drug Discovery: Volume 1
53: Synthetic Methods in Drug Discovery: Volume 2
54: Drug Transporters: Role and Importance in ADME and Drug
1 Development
0
P0 55: Drug Transporters: Recent Advances and Emerging Technologies
F
7- 56: Allosterism in Drug Discovery
9
05 57: Anti-aging Drugs: From Basic Research to Clinical Practice
1
80 58: Antibiotic Drug Discovery: New Targets and Molecular Entities
8
17 59: Peptide-based Drug Discovery: Challenges and New Therapeutics
8
97 60: Drug Discovery for Leishmaniasis
9/
3 61: Biophysical Techniques in Drug Discovery
0
1
0. 62: Acute Brain Impairment Through Stroke: Drug Discovery and
1
oi: Translational Research
d
g | 63: Theranostics and Image Guided Drug Delivery
or
c.
s
s.r
b
u
p
p://
htt
n
o
8
1
0
2
y
ar
u
n
a
J
2
. n 0
o
d
e
h
s
bli
u
P
How to obtain future titles on publication:
A standing order plan is available for this series. A standing order will bring
delivery of each new volume immediately on publication.
For further information please contact:
Book Sales Department, Royal Society of Chemistry, Thomas Graham House,
Science Park, Milton Road, Cambridge, CB4 0WF, UK
Telephone: [phone], Fax: [phone]
Email: [email protected]
Visit our website at www.rsc.org/books
View Online
Theranostics and Image Guided
Drug Delivery
1
0
0
P
F
7-
9
5
0
1
0
8 Edited by
8
7
1
8
7
9 Maya Thanou
9/
3
0 King’s College London, UK
1
10. Email: [email protected]
oi:
d
g |
or
c.
s
s.r
b
u
p
p://
htt
n
o
8
1
0
2
y
ar
u
n
a
J
2
. n 0
o
d
e
h
s
bli
u
P
View Online
1
0
0
P
F
7-
9
5
0
1
0
8
8
7
1
8
7
9
9/ Drug Discovery Series No. 63
3
0
1
0. Print ISBN: 978-1-78262-466-0
1
oi: PDF ISBN: 978-1-78801-059-7
d
g | EPUB ISBN: 978-1-78801-393-2
or ISSN: 2041-3203
c.
s
bs.r A catalogue record for this book is available from the British Library
u
p
p:// © The Royal Society of Chemistry 2018
htt
n
o All rights reserved
8
1
0
y 2 Apart from fair dealing for the purposes of research for non-commercial purposes or for
ar private study, criticism or review, as permitted under the Copyright, Designs and Patents
u
an Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may
J
. on 02 npeortm beis rseiopnro idnu wceridt,i nstgo oref dT hoer Rtroaynaslm Siottceiedt,y i no fa Cnhy efmorimst royr obry tahney c ompeyarnigsh, tw oitwhnoeurt, tohre i np rior
d
e the case of reproduction in accordance with the terms of licences issued by the Copyright
h
blis Licensing Agency in the UK, or in accordance with the terms of the licences issued by the
Pu appropriate Reproduction Rights Organization outside the UK. Enquiries concerning
reproduction outside the terms stated here should be sent to The Royal Society of
Chemistry at the address printed on this page.
Whilst this material has been produced with all due care, The Royal Society of Chemistry
cannot be held responsible or liable for its accuracy and completeness, nor for any
consequences arising from any errors or the use of the information contained in this
publication. The publication of advertisements does not constitute any endorsement by
The Royal Society of Chemistry or Authors of any products advertised. The views and
opinions advanced by contributors do not necessarily reflect those of The Royal Society of
Chemistry which shall not be liable for any resulting loss or damage arising as a result of
reliance upon this material.
The Royal Society of Chemistry is a charity, registered in England and Wales, Number
207890, and a company incorporated in England by Royal Charter (Registered No.
RC000524), registered office: Burlington House, Piccadilly, London W1J 0BA, UK,
Telephone: [phone].
For further information see our web site at www.rsc.org
Printed in the United Kingdom by CPI Group (UK) Ltd, Croydon, CR0 4YY, UK
7
0
0
P
F
7-
9 Preface
5
0
1
0
8
8
7
1
8
7
9
9/ Future and emerging technologies in drug therapy may include a certain
3
0
1 element of imaging. The recent advances in imaging have opened the route
0.
oi:1 for the development of a new type of non-invasive treatment named inter-
d ventional radiology. Interventional Radiology includes a range of therapies
g |
or which rely on the use of image guidance, such as fluoroscopy, ultrasound,
sc. or magnetic resonance imaging (MRI) to precisely target treatments. Most
s.r
b of these techniques are minimally invasive or non-invasive treatments. Usu-
u
p
p:// ally termed as image guided surgery these techniques combine imaging with
htt radiofrequency ablation, electromagnetic radiation, microwaves, light, and/or
on high intensity focused ultrasound for the focal modulation of the tempera-
8
1 ture of the target (hyperthermia and/or ablation) with the aim to remove
0
2
y lesions and unhealthy tissues. Image guided drug delivery is a much-
ar
u related novel concept and another emerging field that aims to optimise drug
n
a
2 J targeting using information provided by real-time medical imaging of the
. n 0 drug and or its carrier. Image guided drug delivery can be used to monitor
o
d biodistribution, as well as drug carrier behaviour such as drug release. In
e
h
blis the clinic, image guided drug delivery can be used to substantially improve
u pharmacokinetics, and therefore the safety and the therapeutic potential of
P
the drug treatment. If the drugs can be imaged while they are in the body,
then it is easy to control their pharmacokinetics and tissue distribution. Sim-
ilar to image guided surgery, image guided drug delivery combines imaging
and drug therapy. Image guided drug delivery employs either sound, light
or electro-magnetic energy to change the state of the drug molecules and
activate them in order to activate their pharmacological action only where it
is required in the body. This provides an excellent method for targeted drug
delivery and therapy. For diseases such as cancer this becomes important
as it is now possible to direct potent cytotoxic drugs to act only in tumours.
For this type of therapy researchers are seeking the development of methods
that do not use ionising radiation for imaging. Furthermore, it is important

Drug Discovery Series No. 63
Theranostics and Image Guided Drug Delivery
Edited by Maya Thanou
© The Royal Society of Chemistry 2018
Published by the Royal Society of Chemistry, www.rsc.org
vii
View Online
viii Preface
to use radiation sources that can be focused in a small defined volume in
the tissue. Theranostics are compounds that are used to diagnose and treat
diseases. Theranostics is a term derived from the words diagnosis and ther-
apy and was coined to define efforts in clinics to develop specific, individual-
7 ized therapies, and to combine diagnostic and therapeutic capabilities into
0
P0 a single agent. Theranostics may be one molecule that carries the probe for
F
7- imaging coupled onto the therapeutic agent (e.g. radiolabelled antibodies) or
9
05 a nanoparticle that is composed of the carrier the imaging probe or material
1
80 and the therapeutic. Emphasis has been given to nanosized theranostics due
8
17 to their potential in cancer treatments. Theranostics play a significant role in
8
97 the development of image guided drug delivery treatments.
9/
3 The scope of the book is to introduce the topic of image guided drug deliv-
0
1
0. ery to the scientific community and highlight its interdisciplinary approach,
1
oi: its efficiency and its translational ability. As such the book covers all recent
d
g | and novel research efforts that address issues of theranostics and image
c.or guided drug delivery. Emphasis has been given to therapeutic concepts that
s
s.r reached clinical trials. Some of these methods are likely to emerge as disrup-
b
u tive technologies in healthcare.
p
p:// The book begins by presenting advances in MRI guided focused ultra-
n htt sound methods and its application in drug delivery. Focused ultrasound
o
8 mediated drug delivery has been applied in several studies with various drug
1
20 molecules to improve their local distribution in diseased tissues. In this case
y
ar an imaging modality such as MRI or ultrasound is used to assess the method
u
an and to provide evidence of drug release. The increased temperature induced
J
2 by focused ultrasound (hyperthermia) can improve blood supply in tissues
. on 0 and therefore improve drug distribution.
d
he Multifunctional nanoagents that combine diagnostic and therapeutic
s
bli functions for antitumor treatments and respond to near infra-red light
u
P are presented. In particular, combining real-time imaging with spatially
precise photothermal therapy mediated by nanoparticles responsive to
near-infrared (NIR, λ = 700–1100 nm) light through conversion of photo
energy into heat. This therapeutic strategy is characterised by its simplicity,
safety, and non-invasiveness, as well as targeting and remote-control release
properties.
The book also describes the magnetic nanoparticles that have found appli-
cation in the clinic, not only as imaging agents, but as a potent tool for treat-
ing tumours. These magnetic nanoparticles have been utilised as imaging
probes for several years. When incorporated with therapeutic agents, they
are specially designed to concentrate at the target site with the aid of mag-
netic force, resulting in theranostic function (therapy and diagnosis). MRI
of magnetic nanoparticles is the most studied imaging application and has
been used in the clinic with high resolution. Furthermore, their use in com-
bination with magnetic field can provide magnetic hyperthermia that can
treat tumours specifically, a concept currently being tested in clinical trials.
The emerging technique of photodynamic therapy is presented and
described. Photodynamic therapy is a clinical technique for the treatment
View Online
Preface ix
of cancers, microbial infections and other medical conditions by means of
light-induced generation of reactive oxygen species using photosensitising
drugs. The intrinsic fluorescence of many such drugs make them potential
theranostic agents for simultaneous diagnosis and therapy. The design and
7 development of these photosensitizers and their carriers will play an import-
0
P0 ant role in designing new photodynamic treatments.
F
7- The book also introduces methods of making theranostic nanomedicines
9
05 for positron emission tomography (PET) imaging. The high sensitivity and
1
80 spatio-temporal resolution of PET makes this non-invasive imaging tech-
8
17 nique ideal for the in vivo tracking of liposomal nanomedicines in the clinical
8
97 setting. This image guided therapeutic approach may eventually allow clini-
9/
3 cians to select patients that would benefit from the nanomedicinal treatment
0
1
0. and, by doing so, enhance the clinical value/efficacy of this promising treat-
1
oi: ment. This is a simple approach that can be used for personalised medicine
d
g | and efficient treatments.
c.or A special chapter is dedicated to the description and preparation of ther-
s
s.r mosensitive liposomes, a tool that is widely used in image guided drug deliv-
b
u ery. The use of thermosensitive liposomes for anticancer treatment, which
p
p:// was first described in the seventies, has gained an increasing amount of
n htt attention over recent years. Various thermosensitive liposome formulations
o
8 have been designed and tested in many different ways, all having various
1
20 advantages and disadvantages. The composition and methods of prepara-
y
ar tion and characterisation are presented in this section.
u
an Within the topic of formulation the book also presents recent advances
J
2 on combining pharmaceutical carriers such as cyclodextrins and image
. on 0 guided focused ultrasound for the targeted release of chemotherapeutics.
d
he Ultrasound-mediated therapeutic drug delivery is one of various methods for
s
bli local drug release and it can also influence cell permeability. Furthermore,
u
P combining it with MRI provides a controllable system for drug release and
impact assessment. The chapter describes the design and development of
carriers for ultrasound activated drug delivery.
For the first time the concept of image guided drug delivery in the gastro-
intestinal tract is presented. Special devices that can be ingested can pro-
vide energy in a controlled and focused manner to effect the tissue. These
ingestible devices could promote drug therapies. Imaging and drug activa-
tion/delivery mechanism can be combined in a miniaturised piece of equip-
ment that can be used in a way similar to capsule endoscopy. This capsule
aims to apply drug therapy as well. This may be the only approach where
image guidance and drug delivery are designed to act in the gut.
The last chapter provides the novel tool of microwaves and describes their
potential as a cost-effective equipment for the development of imaging sens-
ing and image guided drug delivery. It is interesting to see that early studies
indicate that microwave energy interacts with nanoparticles that can affect
the dielectric properties of the biological tissue. It is expected that the ther-
anostic nanoparticles for this technology may be different compared to the
ones mentioned above used by other techniques.
View Online
x Preface
Overall, this book aims to present the most advanced concepts designed
and currently tested in image guided drug delivery. There are concepts that
are more studied than others and are now in clinical trials, such as thermo-
sensitive liposomes and magnetic nanoparticles. There are however novel
7 concepts such as photothermal and microwave therapy that are still at very
0
P0 early stage. For these the optimal chemical formulations have yet to be devel-
F
7- oped and delivered.
9
05 Although the concept of image guided drug delivery is a very recent one
1
80 there are hundreds of studies presented and several strategies have moved
8
17 rapidly to clinical trials to tackle unmet clinical needs. Image guided drug
8
97 delivery methods hold promise to provide revolutionised methods of treat-
9/
3 ing diseases.
0
1
0.
1 Maya Thanou
oi:
d
g |
or
c.
s
s.r
b
u
p
p://
htt
n
o
8
1
0
2
y
ar
u
n
a
J
2
. n 0
o
d
e
h
s
bli
u
P