Nanoscale Imaging Probes for Nanoscale Imaging Probes for Personalized MedicinePersonalized Medicine

Undergraduate ResearchersUndergraduate Researchers

Leslie Chan, Rahul Balusu and Alice ChanLeslie Chan, Rahul Balusu and Alice Chan

MentorsMentors

Efstathios Karathanasis, PhD Efstathios Karathanasis, PhD Ravi V. Bellamkonda, PhDRavi V. Bellamkonda, PhD

Biomedical Engineering, Georgia Tech/EmoryBiomedical Engineering, Georgia Tech/Emory

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Nanotechnology for Solid Nanotechnology for Solid TumorsTumors

Many nanotherapeutics are currently Many nanotherapeutics are currently under clinical evaluation or in under clinical evaluation or in clinical use (clinicaltrials.gov)…clinical use (clinicaltrials.gov)…

The promise...The promise... Multi-functionalityMulti-functionality

TargetingTargeting Non-invasive trackingNon-invasive tracking Diagnostic and therapeutic capabilitiesDiagnostic and therapeutic capabilities

Promise of personalized nanotherapyPromise of personalized nanotherapy

Long Blood Residence Time

Repeated passage throughtumor’s microvascular bed

Enhanced accumulation in“leaky” vasculature Some tumors are not “leaky”

FACT: Nanocarriers need to get to the FACT: Nanocarriers need to get to the tumors to do their ‘magic’…!!tumors to do their ‘magic’…!!

EnhancedPermeation &

Retentionphenomenon

Each tumor is different

No prior knowledge of tumor’s status to optimize therapy No prior knowledge of tumor’s status to optimize therapy protocol; type of systemic chemotherapy, dosimetry and dose protocol; type of systemic chemotherapy, dosimetry and dose

frequencyfrequency

Currently...Currently... One dose fits allOne dose fits all

Multifunctional agent for patient-specific therapy: Multifunctional agent for patient-specific therapy:

A nanoscale probe and a drug-carrierA 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 tumorPre-treatment Pre-treatment

CT/MR scanCT/MR scan-Nanoscale probe-Nanoscale probe-CT or MR scan-CT or MR scan

-Nanocarrier tumor -Nanocarrier tumor distributiondistribution

TreatmentTreatment-Nanocarrier -Nanocarrier

with contrast agent with contrast agent

& drug& drug-Monitor treatment -Monitor treatment

Consider Consider alternative alternative treatmentstreatments

CRITERIONCRITERIONGoodGood

candidate for candidate for Nano-therapyNano-therapy

YES

NO

AdjustAdjust dosage/frequencydosage/frequencyfor for optimaloptimal result result

PERSONALIZED BREAST CANCER PERSONALIZED BREAST CANCER DIAGNOSIS AND THERAPYDIAGNOSIS AND THERAPY

USING THE USING THE NCTXNCTX IMAGING NANOPROBE IMAGING NANOPROBE

50-100nm

Contrast Agent and/ or Drug

t1/2~55hrs100nm diameters

150 mg/mL of Iodine

GE Healthcare Senographe Essential

Personalized Nano-Oncology Personalized Nano-Oncology for Breast Cancerfor 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

Pre-contrastPre-contrast

‘‘Nano-probing’ using mammographyNano-probing’ using mammography

Breast tumor

Cell line: 13762 MAT B IIIrat mammary adenocarcinoma

Fisher F344 rat

Pre-contrastPre-contrast Post-contrastPost-contrast

Dose: 800 mg Liposomal Iodine / Kg body weight

Normal vasculature enhancemen

t

Tumorvasculature enhancemen

t

‘‘Nano-probing’ using mammographyNano-probing’ using mammography

Pre-contrastPre-contrast Post-contrastPost-contrast

Dose: 200 mg Liposomal Iodine / Kg body weight

Liposomesin tumor

72-hr post-72-hr post-contrastcontrast

Liposomes in

spleen

No vasculature

enhancement

Different animal

‘‘Nano-probing’ using mammographyNano-probing’ using mammography

Pre-contrastt=0

Post-contrastt=24 hrs

Spleen

TumorTumor

TumorTumor

SpleenSpleen

Post-contrastt=72 hrs

Post-contrastt=120 hrs

Time course monitoringTime course monitoring

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

y = -0.576x + 0.174R² = 0.838

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.1 0.15 0.2 0.25 0.3

Kenha

ncem

ent

(day

s-1)

Ktumor growth (days-1)

Experimental

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

0

50

100

150

200

6 7 8 9

Gre

y le

vel v

aria

tion

Days after tumor inoculation

Good prognosisBad prognosis

p=0.0009

p<0.0001

Prediction of chemotherapeutic efficacy Prediction of chemotherapeutic efficacy using the NCTXusing the NCTX

0100020003000400050006000700080009000

6 7 8 9 10 11 12 13 14 15 16

Tum

or v

olum

e (m

m3 )

Days after tumor inoculation

CONTROLGood prognosisBad prognosis

†,‡ †,‡ †,‡ †,‡ †,‡

*

*

*

ConclusionsConclusions

Nanotherapy can enable Nanotherapy can enable personalized tumor therapy by personalized tumor therapy by facilitating real-time imaging of facilitating real-time imaging of pharmacokinetics and tumor pharmacokinetics and tumor probing in patientsprobing 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