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

MolecularImagingforCancerVisualization-Outline

•  Preclinicalmousemodels•  Optionsformolecularimagingoftumors•  Currenttechnologyforfluorescenceguidedsurgerythatisavailableintheclinic

•  Futuredirections

Orthotopic injection of pancreatic cells

46 days 50 days

57 days 64 days

Whole body Imaging

P P

P P

O O

O O

S S

S S

B

B B

B

Primary Pancreatic Tumor

0

40

80

120

160

40 46 50 57 64

Spleen Metastasis

0

20

40

60

80

40 46 50 57 64

Bowel Metastasis

0

20

40

60

80

100

40 46 50 57 64

Omental Metastasis

0

20

40

60

80

100

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

HumanizedAntibodies

Foltz et al. Circulation. 2013

HumanizationofAnti-CEAAntibody(M5A)

Yazaki et al. PEDS 2004

CDR grafting onto Herceptin framework

Dr Paul Yazaki City of Hope,

Beckman Research Institute

PET Imaging Using 64Cu-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.

64Cu-M5A scan at 7 weeks post RT – primary and nodal uptake at 24 and 48 hours Surgical resection of primary planned

Imaging Biomarkers: ICG & IRDye800 CW Spectral Overlap: ICG & IRDye800

StrykerAIM

FluorescenceImagingintheOR

Intuitive Firefly

Novadaq Pinpoint

Stryker Aim

IntegrationwithSurgicalTechnology

Imaging with the Firefly Camera, Intuitive Da Vinci Robot System

Cetuximab-IRDye800formultimodalityopticalimaging:Potentialforguidingsurgical

therapyandpathologicalanalysis

EbenRosenthal,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.

FolateReceptorTargeting

OTL38andlungcancer

Sunil Singhal, MD

IndocyanineGreenICG

ParathyroidectomywithICG

•  17yofemale•  Calcium11.9•  PTH113•  Kidneystones•  Bonepain•  Sestamibiscanandultrasoundwerenegative

ParathyroidectomywithICG

•  17yofemale•  Calcium11.9•  PTH113•  Kidneystones•  Bonepain•  Sestamibiscanandultrasoundwerenegative

ParathyroidectomywithICG

LaparoscopicAdrenalectomywithICG

•  27yearoldfemalewithCushing’ssyndrome

•  5cmmassinleftadrenalgland

LaparoscopicLeftAdrenalectomywithICG

Hisataka Kobayashi, MD, PhD NCI

Miguel Garcia Guzman, PhD Aspyrian Therapeutics

Conclusions

•  Curativesurgeryisdependentonremovingallprimaryandmetastaticcancercells

•  Techniquesinfluorescenceguidedsurgery(FGS)areemergingthatselectivelyilluminatecancercells

•  FGSenhancestumordetection,surgicalnavigation,marginconfirmation,andinsomecasescanbecombinedwiththerapeutictechniquestoeliminatemicroscopicdisease

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