Cover Page
The handle
http://hdl.handle.net/1887/66717
holds various files of this Leiden University
dissertation.
Author: Tummers, W.S.F.J.
Willemieke Tummers
Diagnostic and Intraoperative
Targeted Molecular Imaging
© W.S.F.J. Tummers 2018 ISBN: 978-94-6332-404-5
Lay-out: Selma Hoitink, persoonlijkproefschrift.nl Printing: GVO Drukkers & Vormgevers
All rights reserved. No parts of this thesis may be reproduced, distributed, stored in a retrieval system or transmitted in any form or by any means, without prior written permission of the author. The research in this thesis was financially supported by Dutch Cancer Society, Stanford Cancer Institute Translational Research Grant, Intuitive Surgical Clinical Robotics Research Grant. Michaël-van Vloten Fonds, Lisa Waller Hayes Foundation, Jo Kolk Studiefonds, McKinsey Grant, and Ketel1 Studiefonds.
Diagnostic and Intraoperative Targeted Molecular
Imaging for Pancreatic Cancer
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op dinsdag 13 november 2018
klokke 15:00 uur
door
Willemieke Suzanne Fokje Josephine Tummers
Promotor
Prof. dr. C.J.H. van de Velde
Co-promotores
Dr. A.L. Vahrmeijer
Dr. R.J. Swijnenburg
Leden promotiecommissie
Prof. dr. J. Burggraaf
Prof. dr. L.F. de Geus-Oei
TABLE OF CONTENTS
Chapter 1 Introduction and thesis outline 7
Part I: Development of Targeted Molecular Imaging for Pancreatic Cancer
Chapter 2 Advances in Diagnostic and Intraoperative Molecular Imaging of Pancreatic Cancer 19
Chapter 3 Tumor characteristics and surgical technical aspects of R1 in
pancreatic cancer surgery 55
Chapter 4 Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma
77
Part II: Validation of Targeted Molecular Imaging for Pancreatic Cancer
Chapter 5 Preclinical development and validation of multimodal probe for the tumor-specific imaging of pancreatic cancer
103
Chapter 6 On-target probes for early detection 127
Part III: Clinical Translation of Targeted Molecular Imaging
Chapter 7 Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection
137
Chapter 8 Guide for Successful Clinical Translation of Optical Imaging Agents for Molecular Imaging 167
Part IV: Clinical Application of Targeted Molecular Imaging for Pancreatic Cancer Chapter 9 Clinical Translation of Integrin αvβ6 Cystine Knot Positron Emission
Tomography (PET) Tracers 203
Chapter 10 Intraoperative Pancreatic Cancer Detection Using Tumor-Specific Multimodality Molecular Imaging 219
Chapter 11 Detection of Visually Occult Metastatic Lymph Nodes Using Molecularly Targeted Fluorescent Imaging During Surgical Resection of Pancreatic Cancer
237
Part V: Future Directions for Targeted Molecular Imaging
Chapter 12 Recommendations for reporting on emerging optical imaging agents to promote clinical approval 257
Chapter 13 General discussion and future perspectives 283
