First Indo-US Bilateral Meet On Molecular Imaging

IUSSTF
Indo-US Science and Technology Forum
Indo-US Workshop on
Applications of Molecular Imaging in Health,

Disease and Drug Discovery
Nov 8-10, 2010
Centre for Cellular & Molecular Biology

Hyderabad - 500 007, India
Co-organized by
arestream
CCMB
IUSSTF
A Note from the Organizers

to
ALL PARTICIPANTS AND SPEAKERS OF THE INDO-US WORKSHOP ON
“APPLICATIONS OF MOLECUALR IMAGING IN HEALTH,
DISEASE AND DRUG DISCOVERY”
NOVEMEBER, 8-10, 2010
at
CCMB, HYDERABAD, INDIA
Imaging of molecules, cells, tissues, organs and whole organisms has been en vogue ever since the first X-ray
images of Albert von Kolliker's ring bearing hand were taken by Wilhelm Conrad Roentgen in 1896. Over the
past century significant advancement has occurred in this field, that has increased the sensitivity and
specificity of biomedical imaging and completely changed the way radiological medicine is practiced. The
first decade of the new millennium has brought even more impetus to the field thus beginning a new era for
the application of “imageology” in a large spectrum of disciplines that includes interactions between small
molecules, understanding higher order brain functions and discovery of new drugs.
The labs in United States have been pioneers in this newly developing science and the National Institutes of
Health has started a new institute specifically targeted for research on biomedical imaging, whose Deputy
Director is attending the workshop. Indian labs are also becoming aware of the power of these
developments and new infrastructure is being established at several institutes where bioimaging will be
practiced extensively. The Indo-US Science and Technology Forum, New Delhi recognized this synergy
between the US and Indian labs and approved a proposal submitted by CCMB, Hyderabad, India and
Carestream Health Inc. Woodbridge, USA to hold this workshop. On behalf of our respective institutions we
are privileged to host a very knowledgeable faculty for the workshop and we warmly welcome all the
participants to CCMB Hyderabad. We are thankful to the Director of CCMB who has graciously extended the
use of all the facilities at CCMB for this workshop.
Hope all of you will have fun and learn new things in the two and a half days that you spend here!
Gopal Pande Rao Papineni

CCMB Carestream Health Inc.
Indo-US Workshop on “Applications of Molecular Imaging in Health, Disease and Drug Discovery” 1
IUSSTF
AGENDA
Indo-US Workshop on
Applications of Molecular Imaging in Health, Disease and Drug Discovery
November 8-10, 2010 Venue: CCMB Lecture Hall
Sunday, the 7th November, 2010

6.00 pm - Arrival and Mixer – CCMB Centre Court
Monday, the 8th November, 2010
8.45 am - Opening Remarks by
Ch. Mohan Rao, Director, CCMB, Belinda Seto, Dy. Director, NIBIB
and Nishritha Bopana, Science Officer, IUSSTF
Session I : Chairperson – Kakarla Subbarao

9:15 to 11:00 am
Molecular Medicine: Present and Future Belinda Seto

NIBBB, Bethesda
Potential of MRI and In-vivo MR Spectroscopy in Disease Process N.R. Jagannathan

AIIMS, New Delhi
11.00 - 11.15 am - Tea/Coffee Break
Session II : Chairperson – Arun K. Gupta

11.15 - 1.00 pm
Pre-Clinical Molecular Imaging Applications in Cancer Research Rheal Towner

AMRC, Oklahoma City
Use of optical spectroscopic and imaging techniques for biomedical diagnosis P.K. Gupta
CAT, Indore
1.00 - 2.00 pm - Lunch Break
Session III : Chairperson – Kit Lam

02.00 - 03.40 pm
Image guided interventions A. K. Gupta

SCTIMS, Thiruvananthapuram
Combined Anatomical and Molecular Imaging with Therapeutics using Shanthi K. Nair
Biocompatible Nanoparticles AIMSRC, Kochi
03.40 - 4.00 pm - Tea Break

4.00 pm - Departure to Golkonda Fort
8.00 pm - Dinner at Taramati
IUSSTF
Tuesday, the 9th November, 2010

Plenary Session IV : Chairperson – Belinda Seto
9.00 – 11.00 am
From combinatorial chemistry to nanoparticles to Kit Lam

cancer imaging and therapy UCDCC, Davis
Imaging RNA in cells and in animals Samit Adhya

IICB, Kolkata
11.00 - 11.15 am - Tea/Coffee Break
Session V : Chairperson – Arvind K. Chaturvedi

11.15 - 1.00 pm
Nano "Solutions" for Therenostics Mark Kester

Penn State Univ., Hershey
Fluorescence based imaging of tumor cells Gopal Kundu

NCCS, Pune
1.00 - 2.00 pm - Lunch Break
Session VI : Chairperson – B. Ravindran

02.00 - 03.40 pm
In vivo cellular imaging and its role in cell therapy Ali Arbab
CMIL, HFH, Detroit
CNMR Investigations of Excitatory and Inhibitory Anant Patel

Neurotransmission in Cerebral Disorders CCMB, Hyderabad
03.40 - 4.00 pm - Tea Break
Session VII : Chairperson - Samit Adhya

4.00 - 04.50 pm
Role of Molecular Imaging in Drug Discovery Mathew Thakur

TJUH, Philadelphia
04.50 – 06.00 pm - POSTER DISCUSSION

06.00 – 07.00 pm Visit to CRF
07.00 – 9.00 pm - Cultural Program and Dinner (CCMB Terrace)
IUSSTF
Wednesday, 10th November, 2010
9.30 - 11.30 am - Panel Discussion

Kakarla Subbarao
Jyostna Rao
John DelliSanti
Surender Reddy
Neeraj Gupta
B.S. Dwarakanath
11.30 – 12.00 Noon - Wrap up
12.00 Noon - Lunch & Disperse
IUSSTF
Indo-US Workshop on “Applications of Molecular Imaging in

Health, Disease and Drug Discovery
Centre for Cellular & Molecular Biology, Hyderabad, India
Nov 8-10, 2010
Organizers
Dr. Gopal Pande Dr. Rao Papineni

Scientist, Centre for Cellular & Molecular Biology Senior Principal Investigator , Res. & Development
Uppal Road, Habsiguda, Hyderabad 500 007 Carestream Health Inc, USA
Email: gpande@ccmb.res.in 4, Research Drive, WoodBridge, CT 06525
Direct Tel: +91-40-27192605, Fax: +91-40-27160311
Email: rao.papineni1@carestreamhealth.com
Tel 203-676-1163 (USA): +91-9177532584 (India)
LIST OF PARTICIPANTS
INVITEES
S. No. Name of the Speaker Institute & Address City Email
Director, Centre for Cellular &

1 Dr. Ch. Mohan Rao Hyderabad ccmb.res.in
Molecular Biology
2 Dr. John DelliSanti CEO, Carestream Health Inc WoodBridge

carestreamhealth.com
3 Dr. Nishritha Bopana Science Officer, Indo-US Science

and Technology Forum New Delhi indousstf.org
SPEAKERS
S. No. Name of the Speaker Institute & Address City Email
From USA
Director of Advanced Magnetic
Resonance Center, 825, Oklahoma
1 Dr. Rheal Towner omrf.org
Northeast, 13th Street City
2 Dr. Mathew Thakur Thomas Jefferson University

Philadelphia mjefferson.edu
Hospital
3 Dr. Mark Kester Distinguished Professor, Penn

State University Hershey, PA mpsu.edu
4 Dr. Ali Arbab Associate Scientist and Director,

Cellular & Molecular Imaging Detroit shfh.edu
Laboratory, Henry Ford Hospital
5 Dr. Kit Lam Chair, Dept. of Biochemistry and

Molecular Medicine, UC Davis Davis, CA Kucdavis.edu
Cancer Centre
Deputy Director, National
6 Dr. Belinda Seto Institute of Biomedical Imaging Bethesda
and Bioengineering
IUSSTF
From India
Dr. Gopal Kundu Scientist, National Centre for Cell kundu

7 Pune
Science com
Head, Laser Biomedical

8 Dr. P.K. Gupta Applications & Instrumentation Indore pkgupta
Division, CAT
Scientist, Centre for Cellular &
9 Dr. Anant Patel Molecular Biology Hyderabad abpateln
Prof. & Head, MRI Facility, jagancom,

10 Dr. R.N. Jagannathan All India Institute of Medical New Delhi jagancom,
Sciences nrjgj@in
11 Dr. Samit Adhya Scientist, Indian Institute of Kolkata samit.res.in

Chemical Biology
Dean, Amrita Institute of

12 Dr. Shanti K. Nair Medical Sciences and Kochi shantinair@edu
Research Centre, naircom
Amrita Lane AIMS Ponekkara Post
Ex-Director, NIMS, kakarlasubbaraocom

13 Dr. Kakarla Subbarao KREST Building, Sheikpet, Hyderabad
Hyderabad. Tel: 23560005
Prof. & Head, Department of

14 Dr. Arvind K. Chaturvedi Radiology and Imaging, Rajiv
New Delhi arvindatcom
Gandhi Cancer Institute &
Research Center
15 Dr. B Ravindran Director, Institute of Life Sciences Bhubaneswar balaraviin

ravindrancom
16 Dr. Arun K Gupta Professor and Head

Department of Imaging Sciences
and Interventional Radiology, Trivandrum gupta@in
Sree Chitra Tirunal Inst. for gupta@com
Medical Sciences & Technology gupta@.com
IUSSTF
PANEL DISCUSSION
1 Dr. Jyotsna Rao Apollo Gleneagles PET CT Centre Hyderabad jyotsnaelcom
2 Dr. Kakarla Subbarao Ex-Director, NIMS, Hyderabad kakarlasubbaraocom
3 Dr. John DelliSanti CEO, Carestream Health Inc. WoodBridge john.dellisanti@carestreammolec.com
4 Dr. Surender Reddy CEO, Vijaya Dignostics Hyderabad
5 Mr. Neeraj Gupta Imperial Life Sciences Gurgaon ncom
6 Dr. B.S. Dwarakanath INMAS Delhi bo in
IUSSTF
PARTICIPANTS
School of Life Sciences, University of

1 Dr. M. Ramanadham Hyderabad Hyderabad mrnsl@in
Scientist, Head, Division of Radiation

2 Dr. B.S. Dwarakanath Biosciences, Institute of Nuclear Medicine & bsd.org
Delhi bsd@iin
Allied Sciences
3 Dr. E.J.J. Samuel Sr. Professor of Physics, Photonics Division,

Vellore jebamonica.in
VIT University
4 Dr. Lakshmi Chelluri Global Hospitals Hyderabad apparusucom
5 Dr. Sujata Mohanty All India Institute of Medical Sciences New Delhi sujmohantyin
Scientist, Centre for Cellular & Hyderabad marshal.in

6 Dr. Marshal
Molecular Biology
Scientist, Centre for Cellular & Hyderabad shashisin

7 Dr. Shashi Singh
Molecular Biology
Scientist, Centre for Cellular & Hyderabad madhuin

8 Dr. N. Madhusudhana Rao
Molecular Biology
Dr. Aleem Scientist, Deccan Medical College Hyderabad aleem

9
Ahmed Khan of Sciences rediffmail.com
Scientist, Centre for Cellular &

10 Dr. Lekha Dinesh Kumar Molecular Biology Hyderabad lekhan
Technical Officer, Centre for Cellular &

11 Mr. G. Srinivas Hyderabad gsri.in
Molecular Biology
STA , Centre for Cellular &

12 Mr. T. Avinashraj Molecular Biology Hyderabad taraj.in
Scientist, Institute of Nuclear Medicine &

13 Dr. Anil Misra Allied Sciences Delhi akmishra.in
14 Dr. N. Harishankar Scientist, National Institute of Nutrition Hyderabad hsnemanicom
Mr. Sachindra National Centre for Cell Science Pune sachindrabiotech@

15
Parashar
IUSSTF
Ms. Sangeeta sangeeta@

16 MCBL, Indian Institute of Science Bangalore
Chakraborty mcbl.in
17 Dr. Daniela Ahl Imperial Life Sciences Gurgaon daniela..com
18 Mr. Jai Raj Imperial Life Sciences Gurgaon jairajom
19 Ms. Supriya Saraswati National Centre for Cell Science Pune
IUSSTF
POSTER TITLES
1. Specificity in Gene Silencing Using Multifunctional Nanoparticles
Rao V. Papineni1, Tao Ji1, Thirupandiyur Udayakumar2, Mohammed M. Shareef2, Mansoor M.
Ahmed2, Alan Pollack2
1
Carestream Molecular Imaging, Carestream Health, Inc., New Haven, CT, USA;
2
Radiation Oncology, University of Miami, Miami, FL, USA.
2. Bisphosphonate targeting to specific skeletal sites in mice with whole body vibration
Rao V L Papineni. Sean Orton, Tao ji, Hans Schmitthenner, William McLaughlin, Douglas
Vizard and Jingyi Pan
Carestream Molecular Imaging, Carestream Health Inc., New Haven, CT
3. Roadmap for molecular imaging in emerging economies-A focus on nuclear imaging

Jyotsna Rao and Rao V. L. Papineni,
Apollo Hospitals and Carestream Health Inc.
4. Safety and efficacy of the human fetal liver derived stem cell transplantation as supportive
modality in the management of end stage Decompensated liver cirrhosis – A2 year follw up
study
Habibullah CM*, Aejaz Habeeb M*, Aleem A. Khan*, Mahaboob V Shaik*, Parveen N*,
Rajendraprasad A*, Mohammed A Aleem*, Srinivas G†, Avinash Raj T†, Santosh K Tiwari*,
Kumaresan K‡ , Venkateswarlu J*, Gopal Pande†, Linda Powers#
*Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences,
Kanchanbagh, Hyderabad, Andhra Pradesh, India.
†Center for Cellular and Molecular Biology, Uppal Road, Hyderabad
‡KK Scan Centre, Somajiguda, Hyderabad
#Vesta Therapeutics, Inc., 801 Capitola Dr., Suite 8, Durham, NC 27713, USA.
5. Techniques to Improve 3D Optical Imaging Quantification and Sensitivity

Jai Raj
Imperial Life Sciences P. Ltd., Gurgaon
6. Invivo imaging of murine bone marrow and human foetal liver cells in SCID & nude mice
T. Avinash Raj1, G. Srinivas1, J. Mahesh Kumar1, Aleem A. Khan2 , Gopal Pande1
1
Center for Cellular and Molecular Biology, Uppal Road, Hyderabad.
2
Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences,
Kanchanbagh, Hyderabad.
7. Evaluation of the autologous bone marrow derived mononuclear cell therapy in the
infarcted myocardium by imaging analysis – a case report
Authors: Alla GK Gokhale., Lakshmi Kiran Chelluri., Kumaresan K.†, Subramanyam G.,
Sudhakar K., Satish Vemuri., Tanya Debnath., Ratnakar KS
Affiliations: Global Hospitals, Lakdi-ka-Pool, Hyderabad., † KK Nuclear Clinic,
Somajiguda, Hyderabad
IUSSTF
ABSTRACTS
IUSSTF
Molecular Medicine: Present and Future
Belinda Seto, Ph.D.

Deputy Director, National Institute of Biomedical Imaging and Bioengineering
Bethesda, USA
Advances in molecular medicine have the potential and promise to transform medicine from the “see
and treat” paradigm to one that emphasizes personalized, predictive and preventive strategies. To
facilitate the transformation, the U.S. National Institutes of Health support and conduct research that
capitalizes on genomic and proteomic data as a basis for developing diagnostic technologies and
targeted therapy at the cellular and molecular levels. As an example, I plan to discuss a research
project that aims to identify circulating cells and molecular markers in blood samples that will
characterize subsets of patients for targeted therapies. The technology involves microfluidic chips
designed with high throughput capability to screen multiple patient blood samples to capture
signature cells with subsequent identification of the disease genomic, proteomic or molecular
signatures. The platform can be developed to integrate these tests such that a comprehensive picture
of the patient's condition is available to the physician. Immediate applications are envisioned in
cancer and potentially atheromatous disease (the two leading causes of death).
The comprehensive platform technologies may transform medicine by: targeting therapies specific
for patients; predicting responsiveness to therapy; monitoring disease progression and treatment
response at the cell/molecular level to expedite consideration of alternative therapies and probing
the fundamental biology of disease resolution or progression. This should lead to more precise
diagnoses, personalized treatment for patient sub-groups, improved outcomes and reduced cost due
to preventing advanced stages of disease.
IUSSTF
Role of in vivo Magnetic Resonance Spectroscopic Imaging (MRSI)

and Diffusion MRI (DWI) in the Evaluation of Prostate Cancer
N. R. Jagannathan
Department of NMR and MRI Facility

All India Institute of Medical Sciences
New Delhi – 110029, India.
Prostate cancer is the most common male cancer in the West and second most common cause of
cancer related deaths. The incidence of prostate cancer in India is however lower but a steady increase
has been observed in recent years especially in urban areas like Delhi and Mumbai. The key to
treatment is the detection of malignancy at an early stage and monitoring the tumor response to
therapy. The challenges in detection, localization and staging of prostate cancer of existing methods
have prompted us to take the investigation of the role of various MR methodologies in a large cohort
of Indian men prior to biopsy.
The identification of suspicious areas of malignancy are normally carried out using magnetic
resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI) and diffusion weighted
imaging (DWI). Till now nearly 250 men were studied using these MR methods in our Institute. Our
data showed that the apparent diffusion coefficient may be a reliable marker to differentiate normal,
benign and malignant prostate tissues similar to the metabolite ratio obtained from MRS. Further; our
results demonstrated that the combined use of MRSI and DWI improved the diagnosis of prostate
cancer.
The role of 3D 1H MRSI in directing TRUS guided biopsy of prostate was also evaluated in a large cohort
of patients. The z – and x – coordinates of the voxels suspicious of malignancy from MRSI were used to
direct TRUS guided needle biopsy. The site of biopsy was confirmed by post biopsy MRI and MRSI. MRI
showed the site of biopsy as hypo-intense area on gradient T2 weighted image (T2*) while the MR
spectrum showed reduced citrate and increased choline.
In this talk, our experience on the use of MRSI and DWI methods in the diagnosis of prostate cancer in
Indian men especially in clinically challenging cases of patients with PSA level in the range of 4 – 20
ng/mL and/or abnormal DRE will be presented.
IUSSTF
Pre-Clinical Molecular Imaging Applications

in Cancer Research
Rheal A. Towner1, Nataliya Smith1, Ting He1, Sabrina Doblas1, Philippe Garteiser1, Debra Saunders1,
Robert Silasi-Mansat2 and Florea Lupu2
1
Advanced Magnetic Resonance Center, and 2Cardiovascular Biology,
Oklahoma Medical Research Foundation
825 N.E. 13th St., Oklahoma City, OK 73104 U.S.A.
Phone: (405) 271-7383
FAX: (405) 271-7254
Email: Rheal-Towner@omrf.org
Magnetic resonance imaging (MRI) and spectroscopy (MRS) play important roles as
diagnostic tools for many cancers, including assessments on tumor growth, angiogenesis,
bio-physical parameters, such as diffusion and perfusion, and response to therapy.
Molecular MRI (mMRI) has made some important contributions in the study of angiogenic,
inflammation and apoptotic markers in cancer. A brief discussion on advances in the
development of mMRI contrast agents will be presented. Examples on the use of high
resolution MRI and MRS at 7.0 Tesla to obtain molecular imaging information on
angiogenesis, inflammation and tumor metabolism in rodent pre-clinical models for gliomas
and hepatocellular carcinomas (HCC) will be presented. The concept of mMRI involves the
coupling of an affinity molecule that recognizes a specific target marker (e.g. vascular
endothelium growth factor receptor 2 (VEGF-R2), c-Met, or inducible nitric oxide synthase
(iNOS)) and MRI contrast signaling agents such as gadolinium-ligand- or iron oxide
nanoparticle (IONP)-based constructs. Chemical shift imaging (CSI) as a method to assess
lipid metabolism in tumor models will also be presented. MR methods offer the unique
opportunity to be used as tools to obtain non-invasive in vivo morphological/anatomical,
vascular, metabolic, functional and molecular information in rodent pre-clinical models in
cancer.
IUSSTF
Use Of Optical Spectroscopic And Imaging Techniques

for Biomedical Diagnosis
P.K. Gupta
CAT, Indore Laser Biomedical Applications and Instrumentation Division,
Raja Ramanna Centre for Advanced Technology,
Indore – 452013, India.
E-mail: pkgupta@rrcat.govt.in
I shall provide an overview of the studies carried out at Laser Biomedical Applications and
Instrumentation Division, RRCAT on the development and utilization of optical techniques for
biomedical imaging and diagnosis. First I shall discuss some representative biomedical imaging
studies carried out using the optical coherence tomography set ups developed at RRCAT. Work
carried out at RRCAT on the use of optical spectroscopy for biomedical diagnosis will be discussed
next and the results of our recent study on a comparative evaluation of the performance of laser
induced fluorescence spectroscopy and Raman spectroscopy for in-vivo diagnosis of the cancer of
oral cavity will be presented. Finally I shall also describe some aspects of the Raman spectroscopic
studies carried out by us on single, optically trapped Red Blood Cells obtained from blood samples
from healthy volunteers and from patients suffering from malaria.
IUSSTF
Image guided Interventions
A.K. Gupta
Professor and Head

Department of Imaging Sciences
and Interventional Radiology,
Sree Chitra Tirunal Inst. for Medical Sciences & Technology
Thiruvananthapuram
Abstract not received
IUSSTF
Combined Anatomical and Molecular Imaging with

Therapeutics using Biocompatible Nanoparticles
Shantikumar Nair and K.Manzoor
Amrita Centre for Nanosciences
Amrita Vishwa Vidyapeetham, Kochi
The authors discuss new methodologies and treatments of cancer using molecular imaging and
targeted therapeutics using non-toxic nanoparticles. At the Amrita Centre for Nanosciences a range
of multifunctional nanoparticles have been developed with combined fluorescence, X-Ray and MRI
contrast capability. When such particles can be targeted to cancer cells there is the possibility of early
detection by both anatomical and molecular imaging modalities including the opportunity of
delivering drugs directly to the cells in question. Efforts are currently under way to target cancer stem
cells in addition to cancer cells to enhance early detection and therapeutic efficiencies. The results of
some of our current studies will be presented at this workshop.
IUSSTF
From combinatorial chemistry to nanoparticles

to cancer imaging and therapy
Juntao Luo1, Kai Xiao1, Yuan-pei Li1, Joyce Lee1, Nianhuan Yao1, Wenwu Xiao1, Yan Wang1, Michael
Kent2, Holland Cheng3, Gangyu Liu4, and Kit S. Lam1*
1
Department of Biochemistry & Molecular Medicine, Division of Hematology & Oncology, UC Davis
Cancer Center, 2Veterinarian School of Medicine, 3College of Biological Sciences, 4Department of
Chemistry, University of California Davis, California
Corresponding author (Kit.Lam@ucdmc.ucdavis.edu)
Recently we have developed a novel amphiphilic polymer (telodendrimer), comprised of linear

polyethylene glycol, lysine and cholic acid, that can self-assemble under aqueous condition to form
stable micelles. The telodendrimer is prepared by Fmoc-chemistry with standard peptide synthesis
methods. Various hydrophobic drugs such as paclitaxel, etoposide, doxorubicin, SN-38, vinblastine,
vincristine, temsirolimus, and bortezomib can be easily incorporated into the nanoparticles with high
loading capacity. This nanoplatform is highly versatile. We can readily tune the particle size by varying
the configuration and composition of the telodendrimer. DiD near infra-red hydrophobic dye can be
used as drug surrogate for loading inside the nanoparticles for in vivo biodistribution studies in nude
mice bearing ovarian cancer xenograft. Particles smaller than 60 nm were found to preferentially
target the tumors, whereas particles at 150nm were found to concentrate at the liver and lung. The
surface chemistry of the nanoparticles can be easily modified by derivatizing the distal polyethylene
glycol tail of the telodendrimers with short oligopeptides comprised of D-lysine or D-aspartate.
Undesirable liver uptake was found to be very high for those nanoparticles with high surface charges,
either positive or negative. In contrast, liver uptake was very low but tumor uptake was very high
when the surface charge was slightly negative, e.g. one aspartate at the PEG terminus of each
telodendrimer. In the last few years, we have use one-bead one-compound combinatorial library
method to identify tumor targeting ligands. Ligation of one of these ligands OA02, that targets αvβ3
integrin, to the nanoparticle surface further improved tumor targeting and intracellular uptake at the
tumor site. In addition to xenograft models, we have also demonstrated that the nanoparticles could
preferentially target spontaneous mammary tumors of PyV-MT transgenic mice. We have just
completed a Phase I study of placiltaxel-loaded nanoparticles in companion dogs with lymphoma and
showed that the drug is safe. A Phase II study of the same preparation in companion dogs with solid
tumor is on-going.
IUSSTF
Imaging RNA in cells and in animals
Sukanta Jash, Biraj Mahato and Samit Adhya
Division of Molecular and Human Genetics,

Indian Institute of Chemical Biology,
4 Raja S. C. Mullick Road, Calcutta 700032, India.
As a part of our ongoing project on RNA therapeutics of mitochondrial disease, we have developed
methods to visualize fluorescent-tagged RNA in living cells and in live animals. The RNA is
prepared by incorporation of Alexa Fluor (AF)-or BODIPY-Texas Red (TR) tagged ribo UTP during in
vitro RNA directed transcription of DNA templates. The corresponding fluorophores can be
excited by 488 and 633 nm lasers respectively. RNA labeled with either fluorophore was taken up
by cultured cells in presence of a protein carrier. Live cell confocal microscopy of cells doubly
labeled with RNA and green (GFP) or red (RFP) fluorescent protein enabled the imaging of specific
steps of the intracellular transport process of the RNA in real time. In addition, we could visualize
its fate in mice after local or systemic administration of BODIPY-TR labeled RNA by live animal
imaging. These developments will facilitate the study of the transport and metabolism of
biologically active RNA in vitro and vivo.
IUSSTF
Nano"solutions" as Theranostics Dihydrosphingosine-1-Phosphate

Triggers Expansion of Antitumor Immune Effectors
During Photoimmuno-Nanotherapy
Brian M. Barth, James M. Kaiser, Sriram S. Shanmugavelandy, Todd E. Fox, Erhan İ. Altinoğlu, Sarah
A. Knupp. Georgina V. Bixler, Robert M. Brucklachen, Willard M. Freeman, Timothy M. Ritty, James
H. Adair, and Mark Kester,
The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
Immunosuppression is a major obstacle to effective treatment of cancer, and can be a contributing

factor to therapy resistance. Several immunosuppressive cells have been identified, including
myeloid-derived suppressor cells (MDSC), and these have been shown to be increased in laboratory
models of cancer as well as cancer patients. MDSCs directly interfere with T cell mediated immunity,
and dendritic and natural killer cell function. Therefore significant effort is underway toward the
development of therapies that decrease MDSCs. The current study demonstrated that a previously
described deep tissue imaging modality, which utilized encapsulation of indocyanine green within a
calcium phosphosilicate-matrix nanoparticle ((ICG-CPSNP), can be utilized as an immunoregulatory
therapeutic agent. The theranostic application of ICG-CPSNPs as a photosensitizer for photodynamic
therapy (PDT) was shown to effectively block tumor growth in murine breast cancer models by
decreasing MDSCs while increasing immune effectors. As phosphorylated sphingolipid metabolites
have been shown to have immunomodulatory roles, it was hypothesized that the reduction of MDSCs
by ICG-CPSNP PDT was dependent upon bioactive sphingolipids. ICG-CPSNP PDT induced a
sphingosine kinase-dependent increase in dihydrosphingosine-1-phosphate (dhS1P). Indeed,
isolated MDSCs were decreased by treatment with dhS1P, but not sphingosine-1-phosphate, while
dhS1P induced a concomitant expansion of antitumor B cells. Adoptive transfer of these dhS1P-
induced B cells into tumor-bearing mice effectively blocked breast cancer tumor growth. Collectively,
these findings revealed that PDT utilizing the theranostic agent ICG-CPSNP, also behaved as a photo-
immunotherapy in breast cancer by prompting a decrease in immunosuppressive MDSCs and an
increase in immune effectors.
Conflict of Interest Disclaimer: Penn State Research Foundation has licensed calcium phosphosilicate
nanotechnology to Keystone Nano, Inc. (State College, PA). J.A. and M.K. are CSO and CMO of
Keystone Nano, respectively.
IUSSTF
In Vivo Imaging of Tumors in Mice using Bioluminescence and

Fluorescence Technologies
Gopal Kundu
Scientist-F, National Centre for Cell Science, Pune 411 007, India;
E-mail:kundu@nccs.res.in
The molecular imaging of tumor growth, angiogenesis and metastasis recently represent a major area
of research for the diagnosis and targeted therapy of many solid tumors in the area of cancer biology.
In vivo bioluminescent and fluorescent imaging allows the non-invasive detection and quantification
of orthotropic, metastatic and spontaneous tumors in the whole body of mouse. Many imaging
technology has been optimized for high sensitivity, such that micro metastases can be detected. An
optimized set of high efficiency filters and spectral un-mixing algorithms allow taking full advantage of
bioluminescent and fluorescent reporters across the blue to near infrared wavelength region. In our
laboratory, we have recently developed many tumors in mice models and the effects of many drugs
have been tested and subsequently these tumors have been analyzed based on bioluminescence
technology. The analysis of some of these tumor images will be demonstrated during this workshop.
IUSSTF
In Vivo Cellular Imaging and its Role in Cell Therapy
Ali Arbab, MD, PhD

Associate Scientist
Cellular and Molecular Imaging Laboratory,
Department of Radiology, Henry Ford Hospital, Detroit, MI, USA
&
Associate Professor
Department of Radiology
Wayne State University School of Medicine, Detroit, MI, USA
Personalized treatment using stem, modified or genetically engineered, cells is becoming a reality in
the field of medicine, in which allogeneic or autologous cells can be used for treatment and possibly
for early diagnosis of diseases. Hematopoietic, stromal and organ specific stem cells are under
evaluation for cell-based therapies for cardiac, neurological, autoimmune and other disorders.
Cytotoxic or genetically altered T-cells are under clinical trial for the treatment of hematopoietic or
other malignant diseases. Before using stem cells in clinical trials, translational research in
experimental animal models are essential, with a critical emphasis on developing noninvasive
methods for tracking the temporal and spatial homing of these cells to target tissues. Moreover, it is
necessary to determine the transplanted cells, engraftment efficiency and functional capability.
Tracking of migration and homing of systemic or locally administered cells using MRI and other
complementary imaging modalities have passed the infancy. Now the technology is in a state where
robust experiments can be designed in translational studies utilizing cellular magnetic resonance
imaging (CMRI), nuclear medicine techniques and optical imaging. Tagging cells with reporter genes,
fluorescent dyes or different contrast agents transforms them into cellular probes or imaging agents.
In this presentation we will discuss the methods to transform cells into probes for in vivo imaging,
along with their advantages and disadvantages as well as the future clinical applicability of cellular
imaging method and corresponding imaging modality.
Points:
1) Potential application of cells as diagnostic and therapeutic probes.
2) In vitro making of potential therapeutic CTLs for malignant diseases
3) Use of stem cells as gene carrier and delivery vehicles
4) Use of multimodality approaches
IUSSTF
13
CNMR Investigations of Excitatory and Inhibitory
Neurotransmission in Cerebral Disorders
Anant B. Patel
NMR Microimaging & Spectroscopy,
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India
Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in the matured
mammalian central nervous system and together account for ~90% neurotransmitter pool in cortex1.
These neurotransmitters play major roles in energy metabolism, cortical excitability, and cognitive
function. It is well established that neuronal astrocytic substrate cycle exists in the brain. In vivo 13C
NMR studies have established that glutamatergic energetics is supported by oxidative glucose
metabolism1,2. Further, GABA contributes significantly to total neurotransmission and glucose
oxidation by neurons in normal brain3. These findings have led to specific predictions about the
fundamental role of glucose in the support of neurotransmitter cycling4,5. Dysfunction in glutamate
and GABA pathways are associated with many neurological and neuropsychiatric disorders. Thus,
glutamate, GABA and glutamine metabolism is of major importance to brain function and cerebral
well-being.
In this presentation, I will discuss the strategy involving infusion of 13C labeled substrates
together with 13C NMR spectroscopy to measure fluxes through glutamatergic and GABAergic
pathways. We are extending these measurements in mice to understand cerebral metabolism in
different cerebral disorders. I will be presenting our recent data for the investigation of flux through
glutamatergic and GABAergic pathways in healthy as well as in various abnormal/diseased conditions
such as neurodegeneration (Parkinson's, Alzheimer's), addiction (nicotine, alcohol).
References: 1. Sibson et al (1998) Proc Natl Acad Sci 95:316. 2. Patel et al (2004) J Cereb Blood Flow
Metab 24:972. 3. Patel et al (2005) Proc Natl Acad Sci 102:5588. 4. Magistratti et al (1998) Science
283:5801. (3) Hyder et al (2005) J Cereb Blod Flow Metab 26:865.
IUSSTF
ROLE OF MOLECULAR IMAGING IN DRUG DISCOVERY

Mathew L. Thakur, PhD
Department of Radiology,
Thomas Jefferson University, Philadelphia, USA
Despite the great strides made in drug discoveries, many diseases have continued to take toll on
human lives and its quality. Recent advances in molecular biology and genomics have resulted into an
increasing number of novel biomarkers. These biomarkers can contribute extensively into the
development of translational medicine to diagnose diseases as well into the design of personalized
medicine to treat diseases. In the development of such drugs, molecular imaging can play a pivotal
role.
Cancer for example, thought to be initiated by genomic modulation at a cellular level, is known to
overexpress key proteins and RNAs of specific signaling pathways. These have become a hallmark of
many cancers, and an array of such biomarkers have been identified. Similarly the resolution of
common infection, in part, is associated with neutrophil apoptosis accelerated by reduction of
prosurvival factors such as lipopolysaccharides (LPS) and certain cytokines such as IL-1B. Apoptotic
neutrophils are presented in the outer layers, with Phosphatidylserine (PS), which is ordinarily
sequestered in the plasma membrane inner leaflet, and provides itself as an excellent target for
localizing infectious foci in vivo, and for monitoring the effectiveness of its treatment.
We hypothesize that targeting such biomarkers with specific fluorophores for optical imaging or with
radiolabeled specific biomolecules such as peptides on peptide nucleic acids for PET or SPECT imaging
of malignant lesions can help to address the challenges of drug discovery.
Examples of investigations from this laboratory will illustrate approaches not only for diagnosis of
diseases but also for their treatment, stratification and to determine the effectiveness of their
therapeutic interventions.
Supported by NIH CA 10923, BB 001809, ISIORR23709, PA ME-03-184, DOE/BER 63055, NIH CO27175,
NIH CA148565 and NuView, Inc.

First Indo-US Bilateral Meet On Molecular Imaging

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First Indo-US Bilateral Meet On Molecular Imaging

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IUSSTF

Indo-US Science and Technology Forum

Applications of Molecular Imaging in Health,

Centre for Cellular & Molecular Biology

A Note from the Organizers

Gopal Pande Rao Papineni

Sunday, the 7th November, 2010

Monday, the 8th November, 2010

8.45 am - Opening Remarks by

Session I : Chairperson – Kakarla Subbarao

Molecular Medicine: Present and Future Belinda Seto

Potential of MRI and In-vivo MR Spectroscopy in Disease Process N.R. Jagannathan

11.00 - 11.15 am - Tea/Coffee Break

Session II : Chairperson – Arun K. Gupta

Pre-Clinical Molecular Imaging Applications in Cancer Research Rheal Towner

1.00 - 2.00 pm - Lunch Break

Session III : Chairperson – Kit Lam

Image guided interventions A. K. Gupta

03.40 - 4.00 pm - Tea Break

Tuesday, the 9th November, 2010

From combinatorial chemistry to nanoparticles to Kit Lam

Imaging RNA in cells and in animals Samit Adhya

11.00 - 11.15 am - Tea/Coffee Break

Session V : Chairperson – Arvind K. Chaturvedi

Nano "Solutions" for Therenostics Mark Kester

Fluorescence based imaging of tumor cells Gopal Kundu

1.00 - 2.00 pm - Lunch Break

Session VI : Chairperson – B. Ravindran

CNMR Investigations of Excitatory and Inhibitory Anant Patel

03.40 - 4.00 pm - Tea Break

Session VII : Chairperson - Samit Adhya

Role of Molecular Imaging in Drug Discovery Mathew Thakur

04.50 – 06.00 pm - POSTER DISCUSSION

Wednesday, 10th November, 2010

9.30 - 11.30 am - Panel Discussion

11.30 – 12.00 Noon - Wrap up

12.00 Noon - Lunch & Disperse

Indo-US Workshop on “Applications of Molecular Imaging in

Dr. Gopal Pande Dr. Rao Papineni

S. No. Name of the Speaker Institute & Address City Email

Director, Centre for Cellular &

2 Dr. John DelliSanti CEO, Carestream Health Inc WoodBridge

3 Dr. Nishritha Bopana Science Officer, Indo-US Science

S. No. Name of the Speaker Institute & Address City Email

2 Dr. Mathew Thakur Thomas Jefferson University

3 Dr. Mark Kester Distinguished Professor, Penn

4 Dr. Ali Arbab Associate Scientist and Director,

5 Dr. Kit Lam Chair, Dept. of Biochemistry and

Dr. Gopal Kundu Scientist, National Centre for Cell kundu

Head, Laser Biomedical

Prof. & Head, MRI Facility, jagancom,

11 Dr. Samit Adhya Scientist, Indian Institute of Kolkata samit.res.in

Dean, Amrita Institute of

Ex-Director, NIMS, kakarlasubbaraocom

Prof. & Head, Department of

15 Dr. B Ravindran Director, Institute of Life Sciences Bhubaneswar balaraviin

16 Dr. Arun K Gupta Professor and Head

1 Dr. Jyotsna Rao Apollo Gleneagles PET CT Centre Hyderabad jyotsnaelcom

2 Dr. Kakarla Subbarao Ex-Director, NIMS, Hyderabad kakarlasubbaraocom

3 Dr. John DelliSanti CEO, Carestream Health Inc. WoodBridge john.dellisanti@carestreammolec.com

4 Dr. Surender Reddy CEO, Vijaya Dignostics Hyderabad

5 Mr. Neeraj Gupta Imperial Life Sciences Gurgaon ncom

6 Dr. B.S. Dwarakanath INMAS Delhi bo in