Transcript chan_lec_undergrad

Nanoscale Imaging Probes for
Personalized Medicine
Undergraduate Researchers
Leslie Chan, Rahul Balusu and Alice Chan
Mentors
Efstathios Karathanasis, PhD
Ravi V. Bellamkonda, PhD
Biomedical Engineering, Georgia Tech/Emory
Nanotechnology for Solid Tumors
Many nanotherapeutics are currently under clinical
evaluation or in clinical use (clinicaltrials.gov)…
The promise...
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Multi-functionality
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Targeting
Non-invasive tracking
Diagnostic and therapeutic capabilities
Promise of personalized nanotherapy
FACT: Nanocarriers need to get to the
tumors to do their ‘magic’…!!
Enhanced
Permeation &
Retention
phenomenon
Long Blood Residence Time
Each tumor is different
Repeated passage through
tumor’s microvascular bed
Enhanced accumulation in
“leaky” vasculature
Some tumors are not “leaky”
No prior knowledge of tumor’s status to optimize therapy protocol;
type of systemic chemotherapy, dosimetry and dose frequency
Currently... One dose fits all
Multifunctional agent for patient-specific therapy:
A nanoscale probe and a drug-carrier
In each specific patient, is their tumor susceptible to nano-therapy?
Our approach: Develop a nano-construct capable of
(1) non-invasive interrogation of tumor status using CT or MRI and
(2) delivery of chemotherapeutics to tumor
Pre-treatment
CT/MR scan
-Nanoscale probe
-CT or MR scan
-Nanocarrier tumor
distribution
CRITERION
Good
candidate for YES
Nano-therapy
Treatment
-Nanocarrier
with contrast agent
& drug
-Monitor treatment
NO
Consider
alternative
treatments
Adjust
dosage/frequency
for optimal result
PERSONALIZED BREAST CANCER
DIAGNOSIS AND THERAPY
USING THE NCTX IMAGING NANOPROBE
t1/2~55hrs
100nm diameters
150 mg/mL of Iodine
Contrast Agent
and/or
Drug
50-100nm
Personalized Nano-Oncology
for Breast Cancer
 Breast cancer statistics...
most common cancer in
women
- Every 3 min. a woman is diagnosed
with breast cancer
- Breast cancer incidence: from 1 in
20 (in 1960) to 1 in 8 (today)
- NCI estimates for 2007: 178,000
new cases / 41,000 deaths
 Mammography: most common
screening tool
- Mammography is a low cost x-ray
- Annual mammogram >40 yrs
- Mammograms have caused a
dramatic reduction of mortality
GE Healthcare Senographe Essential
‘Nano-probing’ using mammography
Pre-contrast
Breast
tumor
Cell line: 13762 MAT B III
rat mammary adenocarcinoma
Fisher F344 rat
‘Nano-probing’ using mammography
Pre-contrast
Post-contrast
Normal
vasculature
enhancement
Tumor
vasculature
enhancement
Dose: 800 mg Liposomal
Iodine / Kg body weight
‘Nano-probing’ using mammography
Pre-contrast
Post-contrast
72-hr postcontrast
Different
animal
Liposomes
in tumor
Liposomes
in spleen
No vasculature
enhancement
Dose: 200 mg Liposomal
Iodine / Kg body weight
Time course monitoring
Tumor
Tumor
Tumor
Spleen
Pre-contrast
t=0
Post-contrast
t=24 hrs
Tumor
Spleen
Post-contrast
t=72 hrs
Spleen
Post-contrast
t=120 hrs
Prediction of chemotherapeutic efficacy
using the NCTX
Prediction of chemotherapeutic efficacy
using the NCTX
Prediction of chemotherapeutic efficacy
using the NCTX
Prediction of chemotherapeutic efficacy
using the NCTX
Kenhancement (days-1)
0.12
Experimental
0.10
y = -0.576x + 0.174
R² = 0.838
0.08
0.06
0.04
0.02
0.00
0.1
0.15
0.2
Ktumor growth (days-1)
0.25
0.3
Prediction of chemotherapeutic efficacy
using the NCTX
200
Good prognosis
Grey level variation
Bad prognosis
150
100
p<0.0001
p=0.0009
50
0
6
7
8
Days after tumor inoculation
9
Prediction of chemotherapeutic efficacy
using the NCTX
9000
CONTROL
Good prognosis
Bad prognosis
Tumor volume (mm3)
8000
7000
6000
*
5000
*
4000
*
3000
2000
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1000
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0
6
7
8
9
10
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12
13
Days after tumor inoculation
14
15
16
Conclusions
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Nanotherapy can enable personalized tumor
therapy by facilitating real-time imaging of
pharmacokinetics and tumor probing in
patients
FUNDING: National Institutes of Health (NCI), National Science Foundation,
Georgia Cancer Coalition, Wallace H Coulter Translational Research Grant,
Nora L. Redman Foundation, GTEC, Marval Biosciences