Department of Medical Biophysics

1
The Department of Medical Biophysics is offering
a NEW COURSE this term.....
Department of Medical Biophysics MBP 518A,
Molecular Imaging ------------------------------
--------------------------------------------------
------------------- Calendar Description This
new course will introduce the role of diagnostic
imaging in detecting molecules, genes, and cells
in vivo. Emphasis will be in how these techniques
can help study molecular mechanisms of disease in
vivo. Topics include DNA/protein synthesis,
transgenic mice, novel contrast agents and small
animal imaging. Students will be evaluated based
on an oral presentation of a journal article and
a written literature review. Weight Half
Course (1 term) When Offered Fall Term
2007 Course Director Savita Dhanvantari sdhanvan_at_
lawsonimaging.ca
2
Course Goals and Objectives GOALS At the end
of this course, students will 1. Have an
understanding of how different imaging modalities
can be used to examine molecular and cellular
processes. 2. Will be able to apply this
knowledge to mechanisms of disease progression
and therapy. OBJECTIVES Students will
demonstrate their mastery of the course content
by 1. Defining the concept of "molecular
imaging." 2. Understanding standard methods and
models in molecular and cell biology 3.
Understanding how imaging modalities are adapting
to image genes, molecules and cells. 4.
Combining their knowledge of imaging with methods
in molecular and cell biology. 5. Applying
concepts of molecular imaging to examining
molecular mechanisms of disease, such as cancer,
cardiovascular disease, diabetes, and
neurological disorders. 6. Critically evaluating
the current literature on molecular imaging. 7.
Predicting how molecular imaging will advance the
understanding of both normal physiology and
disease progression, from both scientific and
clinical perspectives.
3
Molecular Biology Lectures
4
Molecular Imaging Lectures
5
Student Presentations
6
Evaluation

• Oral presentation 40
• You will choose a journal article to present
• Article must NOT be related to your thesis topic
• Article must contain all the elements of
  molecular imaging molecular biology (clonal
  cells, animal models, stem cell biology,
  protein-protein interactions), chemical probe
  design, and imaging
• 15 min presentation, 5 min discussion (20 min
  total)
• Everyone will participate in evaluation!
• Sample topics Image-guided stem cell therapy
• Imaging transplanted islets and islet
  regeneration
• Imaging cancer and tumours
• Cardiovascular imaging
• Brain mapping
• Imaging infectious disease
• Imaging protein-protein interactions
• Drug delivery applications

7
Oral Presentation Score Sheet
8

• Written evaluation 40
• Based on the article selected for oral
  presentation, select up to 10 additional key
  articles. Based on these articles, a 5-page
  minireview will be written as follows
• Abstract 150 word summary
• Introduction one paragraph introducing the
  subject/disease/molecular process
• 2-3 sections discuss articles critically use
  sections to divide up into imaging modalities,
  different probes within same modality, different
  biological approaches, etc. Include
  figures/tables with appropriate acknowledgements.
• Conclusion Where does the field stand currently?
  What questions remain unresolved? Where will it
  move in the future? What improvements in probe
  development/ imaging parameters are required to
  answer the next big biological question?
• References (not included in page limit).

9
The rest of the evaluation.

• Attendance and participation in class 10
• Ask questions, initiate discussion, responding
  to instructors prompts/questions
• Be an Active Participant!

10

• Attendance at invited lecture 10

Dr. Youssef Wadghiri Department of Radiology, New
York University School of Medicine Friday,
November 9 Journal Club 1100 am Talk 1200 pm
Come prepared to discuss the following articles
with Dr. Wadghiri Wadghiri YZ, Johnson G,
Turnbull DH. Sensitivity and performance time in
MRI dephasing artifact reduction methods. Mag Res
Med. 2001 45470-476. Wadghiri YZ, Sigurdsson
EM, Sadowski M, Elliott JI, Li Y, Scholtzova H,
Tang CY, Aguinaldo G, Pappolla M, Duff K,
Wisniewski T, Turnbull DH. Detection of
Alzheimers amyloid in transgenic mice using
magnetic resonance microimaging. Mag Res Med
2003 50 293-302.
11
And here are some VERY COOL examples of what
youll be learning about.....
12
Molecular Imaging in Cardiovascular Disease
13
Tracking stem cells in vivo applications for
regeneration of cardiac tissue after myocardial
infarct
14
Targeted microbubbles for ultrasound imaging of
vascular remodelling induced by FGF-2
Model post-ischemic angiogenesis results in
increased integrin expression
Control
Biomarker integrin expression after treatment
with FGF-2
FGF-2
Imaging probe US microbubbles conjugated to
echistatin
Leong-Poi et al Circulation 1113248, 2005
15
Molecular Imaging in Cancer
16
Imaging a Biomarker of Prostate Cancer Using
SPECT/CT
Model PMSA-expressing prostate cancer tumour
cells injected into mice
Biomarker PMSA in prostate cancer cells
Imaging probe 125IDCIT for SPECT imaging of
PMSA-positive tumours
Foss et al Clin Cancer Res 114022, 2005
17
Imaging Tumour Biomarkers Using Fluorescence
Model integrin-expressing subcutaneous tumour
xenografts
Biomarker avb3 integrin
Imaging probe RGD-Cy5.5
Chen et al Cancer Res 648009, 2004
18
Imaging Cancer Therapy
Luciferase as a reporter for apoptosis
Model human glioma cell line transplanted into
mice
Biomarker caspase-3, a signalling molecule in
apoptosis
Imaging probe caspase-3-activatable luciferase
construct
Laxman et al PNAS 9926, 2002
19
Molecular Imaging in Diabetes
20
Can islet transplant rejection be imaged with MRI?

• 1000 labelled human islets infused into hepatic
  portal vein of Balb/C or NODscid mice
• 4.7T MRI over 14 days showed disappearance of
  Feridex from islets
• Acute rejection, not long-term monitoring of
  islet Tx status

Evgenov et al 2006 Diabetes 552419
21
Imaging Transplanted Islets Using PET Reporter
Genes

• Adsr39tk islets in liver of NOD/SCID mice
• Signal detected to 40 days
• Blood glucose remained normal

Lu et al 2006 PNAS 10311294 Lu et al 2006 Mol
Therapy
22
Optical Imaging Shedding Light On Islet
Transplant Status
Park et al 2005 Genesis 4380 MIP-luc transgenic
mouse
Chen et al 2006 Transplantation 811421 Early
detection of islet transplant rejection
RIP-luc islets transplanted under kidney capsule
of allogeneic diabetic recipients