stanford...stanford cancer’imaging’training’program’ superparamagne/c)) ironoxide) endorem!...
TRANSCRIPT
Stanford Cancer Imaging Training Program
Superparamagne/c Iron Oxide
Endorem
Cliavist
Combidex
Supravist
Clariscan
Core
Coa'ng
FDA Approved
150 nm
100 nm
40 nm
30 nm
20 nm
Ferumoxytol (Feraheme , Rienso )
Carboxymethyl Dextran 20-‐30 nm
Background: Superparamagne'c Iron Oxide Nanopar'cles
Stanford Cancer Imaging Training Program
Superparamagne'c Iron Oxide Nanopar'cles
Applica/ons and Developments in Therapy
The treatment of tumors using targeted SPIO
Targeted SPIO bind specifically to the tumor receptor which selec'vely suppresses tumor growth Targeted SPIO are used for magne'cally induced hyperthermia aNer tumor binding Targeted SPIO are loaded with therapeu'c agents (drug targe'ng) and these accumulate in the target 'ssue
1
2
3
4
1
2
3
ΔT
NIR SPIO 1 2 3
Stanford Cancer Imaging Training Program
Background: Superparamagne'c Iron Oxide Nanopar'cles
Applica/ons and Developments in Diagnos/cs and Therapy
SPIO in preclinical and experimental applica/on Molecular imaging SPIO conjuga/on with an/bodies and an/body fragments Tumor imaging Apoptosis imaging Cardiovascular imaging Cell labeling and cell imaging in MRI Transplant diagnos/cs, imaging of rejec/on reac/ons (graK rejec/on) Inflamma/on, infec/on, and adiposity imaging Imaging of mul/ple sclerosis (MS) and neurodegenera/on Metabolic imaging Imaging of enzyma/c ac/vity AND…
SPIO in clinical applica/on T2/T2* applica/ons: Liver imaging Spleen imaging Lymph node imaging Tumor imaging Bone marrow imaging Imaging of the gastrointes/nal tract CNS imaging Characteriza/on of atherosclero/c plaques
Stanford Cancer Imaging Training Program
Objectives
To evaluate the mechanisms that lead to cancer growth inhibi/on via local injec/on of iron oxide nanopar/cles into early tumor deposits
Objectives
Immune responses in solid tumors
DeNardo D and Coussens L 2010
J Clin Invest. 2011;121(3):985–997
Iron Oxides cause M1 polariza/on
Stanford Cancer Imaging Training Program
Iron oxide nanopar/cles ini/ate a proinflammatory immune response, based on macrophage influx into tumors and M1 polariza/on
Hypothesis
Hypothesis
Stanford Cancer Imaging Training Program
O2+1.5% Isoflurane
MMTV PyMT-‐derived cells Postpubertal female FVB/n mice
2.3 million Cells to the leN lower mammary fat pad
Methods: in vivo studies
100 Micro liWer
ICE/4 C
Stanford Cancer Imaging Training Program
O2+1.5% Isoflurane
Postpubertal female FVB/n mice
Methods: in vivo studies
100 Micro liWer
ICE/4 C
+
Cancer Cells
Iron Oxides
10mg/kg Ferumoxytol + Cancer Cells
27.92 mg/kg Ferumoxytol + Cancer Cells
10mg/kg Ferumoxtran-‐10 + Cancer Cells
A
B
C
A 2.3 million Cells + B C or or
to the right lower mammary
1
2
Stanford Cancer Imaging Training Program
Conclusion
Iron oxide nanopar'cles ini'ate a proinflammatory immune response, based on macrophage influx into tumors and M1 polariza'on
This finding has important implica'ons for diagnos'c and theranos'c applica'ons of iron oxide nanopar'cles
Iron oxide nanopar'cle-‐delivery to tumors may support M1-‐ac'va'ng immunotherapies, such as the upcoming an'-‐CD47 therapy at Stanford
Stanford Cancer Imaging Training Program
Thank you