Nanomedicine Keon Wook Kang MD Ph D Department

Nanomedicine Keon Wook Kang, MD, Ph. D Department of Nuclear Medicine Seoul National University College of Medicine

1960. 5. 30

Nanomedicine Medical application of nanotechnology (< 100 nm) Ultrasensitive nano sensing Biomarker nano imaging Selective nano drug delivery Nano tissue engineering

TRANSLATIONAL RESEARCH

Translational Research Bench to Bed Luminometer IVIS micro. PET Clinical PET

Molecular Imaging Equipments in SNUH Animal PET/CT PET/MRI under develop RF coil Animal SPECT/CT PET under develop PET detector IEEE Nucl Sci, 2008 In Vivo Optical Imaging System Xenogen IVIS 100 In Vivo Fluorescent Imaging System Cyclotron

MULTIMODAL IMAGING

Overview of small animal imaging systems Technique Cost PET Resolution Depth Time Sensitivity 1 -2 mm No limit Min 10 -11 – 10 -12 mole/L $$$ SPECT 1 -2 mm No limit Min 10 -10 – 10 -11 mole/L $$ MRI 10 -100 μm No limit Min-hr 10 -3 – 10 -5 mole/L $$$ CT 50 μm No limit Min not well characterized $$ cm Min 10 -15 – 10 -17 mole/L $$ 10 -9 -10 -12 mole/L $ Bioluminescence Imaging Fluorescence Imaging several mm 1 -2 mm < 1 cm Sec-min

PET/CT M/51 A. Colon Ca. Rt hemicolectomy Rising CEA Bx - metastatic adenocarcinoma

Sentinel node detection Radiolabeled nanocolloids

Quantum Dots Cd. Se Kim Sungjee Nat Biotechnol 2004

PET/CT/Optical Multimodal SND Using Ga-68 RITC Silica Nanoparticles s. c. injection on the left foot pad PET/CT ex vivo fluorescence in vivo fluorescence TEM imaging nano-silica Jeon YH et al. Mol Imaging Biol 2009

Sentinel node detection using PET/MRI/fluorescent imaging 68 Ga-SCN-NOTA-MNP-Si. O 2 (NIR 797) 30~50 nm 2009 World Molecular Imaging Conference Funded by KRIBB

Courtesy of Lim YT 연강재단연구 Troyan, Ann Surg Oncol 2009

Surgical guide using PET/MRI/fluorescent nanoimaging PET/MRI

바이오마커 나노영상을 이용한 COMPANION DIAGNOSTICS

Market of EGFR cancer therapy • In 2005, $3 billion market-drugs – trastuzumab (Herceptin; Genentech) – cetuximab (Erbitux; Im. Clone Systems) – erlotinib (Tarceva; OSI Pharmaceuticals) – gefitinib (Iressa; Astra. Zeneca) • Recent entry – panitumumab (Vectibix; Amgen) – lapatinib (Tykerb; Glaxo. Smith. Kline) • Current development – 46 novel agents (2/3 clinical trials)

Response rates of targeted therapy • Iressa (Gefitinib) in NSCLC – overall US response rate only 10% (n = 216) • women and adenocarcinoma ~ 17%, men and smokers ~ 5% – response rate 25 -30% in Japan – Incidence of interstitial lung disease 2% in Japan & 1/3 of ILD patients died • Erbitux (Cetuximab) in colon cancer – In the U. S. and European trials, the response rate 10 -11% as a single agent, and double when combination with irinotecan.

Assessment of HER 2 Status IHC using rabbit Ab (DAKO) HER 2 protein overexpression FISH HER 2 gene amplification

IHC FISH

QD-Herceptin conjugate finds out Her 2 over expressed Herceptin-resistant breast cancer cell SK-BR-3 JIMT-1

Development and Clinical Application of New HER 2 Test Using Nano-molecular Imaging in Patients with Breast Cancer Patent A KIT FOR DIAGNOSIS OF BREAST CANCER USING HERCEPTIN, A COMPOSITION COMPRISING HERCEPTIN AND A METHOD FOR DETECTING HERCEPTIN-SENSITIVE HER 2 OVEREXPRESSED CELL USING THE SAME. Applicant(s): NATIONAL CANCER CENTER, LEE, Eun Sook; KANG, Keon Wook; YOO, Byong Chul; LEE, Ho-Young; KONG, Sun Young; KANG, Se Hun; BAEK, Nam Suk; KWON, Bu-Mi; KWON, Young Mi, International Application No. : PCT/KR 2008/006127, International Filing Date: 16. 10. 2008

Multiplexing imaging using Raman spectroscopy with SERS dots Antibody conjugated SERS dots Patients’ tissue In vivo Raman spectrometer In vivo imaging

Biomarker Targeting THERAGNOSIS

PAMAM Dendrimers (G= 9) (G= 1 -5) (G= 3 -7) (G= 8) Donald A. Tomalia, Ph. D.

Biodistribution of nanoparticles 30 nm silica nanoparticles in a mouse NIR Imaging Before injection Just after injection 1 h after injection 1 hr after injection 3 h after injection 2 hr after injection 30 nm gold nanoparticles in a mouse PET/CT

125 I-labeled cyclic RGD peptide-gold nanoparticle 125 I-c. RGD-gold nanoparticles tumor Cold blocking test tumor 125 I-gold nanoparticles tumor In vivo SPECT/CT imaging of in a U 87 MG tumor bearing mouse

Biodegradable Non-biodegradable • • • Albumin nanocolloids Micelles, liposomes USPIOs Dendrimers Polymeric nanoparticles – Chitosan – PLGA Quantum dots Silica nanoparticles Carbon nanotubes, fullerenes Gold nanoparticles Dendrimers Polymeric nanoparticles – Polystyrene – Polybutylcyanoacrylate

Cancer targeted imaging using leukocyte mimic liposome Sialyl-Lewis. X-liposome-Cy 5. 5 Tumor GLYCOLIPO™ K 1

NH 2 Theragnosis using multimodal multiplexing molecular imaging NH 2 NH 2 Proteome library Aptamer Multimodal multiplexing molecular imaging Multifunctional nanoparticles Targeted therapy

Personnel in Nucl Med, SNUH Faculty: 17 MD: 11 / Ph. D: 6 (Physics, Chemistry, Molecular Biology) 본원 DS Lee MC Lee KW Kang JC Paeng 분당 JK Chung SE Kim YK Kim 보라매 본원Ph. D WW Lee HY Lee JM Jeong JJ Lee SW Oh YS Lee Fellow: 2, Residents: 12 Postdocs: 3, Students/ Staffs: 53 JS Lee HW Youn DW Hwang

BIT Port l 160 acre in Incheon Free Economic Zone l Period: 2015~, Budget: 250 mil USD l 10 R&D centres and a research hospital l Nano-molecular Imaging Center

Probes +Sensor = System 화학 생물 공학 의학 In vivo Raman spectroscopy system Photoacoustic tomography system Nano-molecular PET/MRI system

Rat. CAP A small, head-mounted PET for imaging the brain of an awake RAT