Molecular Imaging for Cancer Visualization American College of Surgeons Surgical Simulation Summit Chicago, IL March 16-17, 2018 Michael Bouvet, MD Professor of Surgery University of California San Diego San Diego VA Medical Center
Molecular Imaging for Cancer Visualization - Outline Preclinical mouse models Options for molecular imaging of tumors Current technology for fluorescence guided surgery that is available in the clinic Future directions
Orthotopic injection of pancreatic cells
Whole body Imaging P O S B P O S B 46 days 50 days P O S B P O S B 57 days 64 days
Primary Pancreatic Tumor Bowel Metastasis 160 120 100 80 80 60 40 0 40 46 50 57 64 40 20 0 40 46 50 57 64 Spleen Metastasis Omental Metastasis 80 100 60 80 40 60 40 20 20 0 40 46 50 57 64 0 40 46 50 57 64 - Bouvet M, Wang J, Nardin SR, Nassirpour R, Yang M, Baranov E, Jiang P, Moossa AR, Hoffman RM. Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model. Cancer Research 62(5):1534-1540, 2002.
Fluorophore Conjugate Antibodies
Cristina Metildi, MD
Ali Maawy, MD
Depth of penetration
PLOS ONE DOI:10.1371/journal.pone.0122100 March 27, 2015
Humanized Antibodies Foltz et al. Circulation. 2013
Humanization of Anti-CEA Antibody (M5A) CDR grafting onto Herceptin framework Dr Paul Yazaki City of Hope, Beckman Research Institute Yazaki et al. PEDS 2004
PET Imaging Using 64 Cu-M5A Anti-CEA mab 55 yo M T3N1 rectal cancer with small lung mets and circulating CEA levels of 142. FDG-PET uptake in large primary tumor and peri-rectal nodes. FOLFOX x 8 with reduction of primary, no change in lung mets (felt benign), and CEA normal. Neoadjuvant chemo-radiotherapy: 54 Gy + capecitabine. 64 Cu-M5A scan at 7 weeks post RT primary and nodal uptake at 24 and 48 hours Surgical resection of primary planned
Imaging Spectral Biomarkers: Overlap: ICG ICG & & IRDye800 CW
Stryker AIM
Fluorescence Imaging in the OR Novadaq Pinpoint Intuitive Firefly Stryker Aim
Integration with Surgical Technology Imaging with the Firefly Camera, Intuitive Da Vinci Robot System
Cetuximab-IRDye800 for multimodality optical imaging: Potential for guiding surgical therapy and pathological analysis Eben Rosenthal, MD
From: Bouvet M, Hoffman RM. Laparoscopic fluorescence imaging for identification and resection of pancreatic and hepatobiliary cancer. In: Kokudo N, Ishizawa T (eds.), Fluorescence Imaging: Treatment of Hepatobiliary and Pancreatic Diseases. Front Gastrointest Res. Basel, Karger, 2013, vol 31, pp. 92-99.
Folate Receptor Targeting
OTL38 and lung cancer Sunil Singhal, MD
Indocyanine Green ICG
Parathyroidectomy with ICG 17 yo female Calcium 11.9 PTH 113 Kidney stones Bone pain Sestamibi scan and ultrasound were negative
Parathyroidectomy with ICG 17 yo female Calcium 11.9 PTH 113 Kidney stones Bone pain Sestamibi scan and ultrasound were negative
Parathyroidectomy with ICG
Laparoscopic Adrenalectomy with ICG 27 year old female with Cushing s syndrome 5 cm mass in left adrenal gland
Laparoscopic Left Adrenalectomy with ICG
Hisataka Kobayashi, MD, PhD NCI Miguel Garcia Guzman, PhD Aspyrian Therapeutics
Conclusions Curative surgery is dependent on removing all primary and metastatic cancer cells Techniques in fluorescence guided surgery (FGS) are emerging that selectively illuminate cancer cells FGS enhances tumor detection, surgical navigation, margin confirmation, and in some cases can be combined with therapeutic techniques to eliminate microscopic disease
Acknowledgements Bouvet lab John DeLong Thinzar Helmi Lwin Jeong Youp Park Ho Kyoung Hwang Siamak Amirfahkri Funding NIH/NCI American Cancer Society VA Merit Review Leo and Anne Albert Trust Intuitive Surgical Research Grant City of Hope John C. Williamson Gagandeep Gaugs Singh Paul Yazaki AntiCancer, Inc Robert M Hoffman Takashi Murakami Yukihiko Hiroshima Sang Nam Yoon University of Nebraska Surinder Batra