Advancing novel molecular imaging agents from preclinical studies to first-in-humans phase I clinical trials in academia--a roadmap for overcoming perceived barriers

Raymond M Reilly; Karen Lam; Conrad Chan; Mark Levine

doi:10.1021/acs.bioconjchem.5b00105

Advancing novel molecular imaging agents from preclinical studies to first-in-humans phase I clinical trials in academia--a roadmap for overcoming perceived barriers

Bioconjug Chem. 2015 Apr 15;26(4):625-32. doi: 10.1021/acs.bioconjchem.5b00105. Epub 2015 Mar 26.

Authors

Raymond M Reilly^{1

2}, Karen Lam¹, Conrad Chan¹, Mark Levine³

Affiliations

¹ †Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.
² ‡Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada M5T 1W7.
³ ⊥Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada L8S 4L8.

PMID: 25781873
DOI: 10.1021/acs.bioconjchem.5b00105

Abstract

There is a critical need to advance promising novel molecular imaging (MI) agents for cancer from preclinical studies to first-in-humans Phase I clinical trials in order to realize their full potential for cancer detection and for predicting or monitoring response to targeted ("personalized") cancer therapies. Steps to clinical translation include radiopharmaceutical formulation, preclinical pharmacology and toxicology studies, clinical trial design and human ethics approval, and regulatory agency submission. In this Topical Review, we provide a "roadmap" to advancing one class of novel MI agents to Phase I trials in academia and illustrate the processes that we have successfully applied for (111)In-labeled pertuzumab, a MI probe for monitoring response of HER2-positive breast cancer to treatment with trastuzumab (Herceptin). We hope that our experience will encourage other academic radiopharmaceutical scientists to embrace this challenge.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antibodies, Monoclonal, Humanized / metabolism
Antibodies, Monoclonal, Humanized / therapeutic use*
Antineoplastic Agents / metabolism
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / diagnostic imaging*
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Breast Neoplasms / ultrastructure
Clinical Trials, Phase I as Topic
Drug Approval
Drug Evaluation, Preclinical
Female
Humans
Indium / chemistry*
Indium / metabolism
Molecular Imaging / methods
Molecular Targeted Therapy
Radionuclide Imaging
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / metabolism
Reagent Kits, Diagnostic
Receptor, ErbB-2 / antagonists & inhibitors
Receptor, ErbB-2 / genetics
Receptor, ErbB-2 / metabolism
Staining and Labeling / methods
Trastuzumab / metabolism
Trastuzumab / therapeutic use*

Substances

Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Radiopharmaceuticals
Reagent Kits, Diagnostic
Indium
ERBB2 protein, human
Receptor, ErbB-2
pertuzumab
Trastuzumab