title: Advancing novel molecular imaging agents from preclinical studies to first-in-humans phase I clinical trials in academia--a roadmap for overcoming perceived barriers.
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.
authors.affiliation: †Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.|‡Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada M5T 1W7.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Reilly
authors.affiliation: †Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.
authors.forename: Karen
authors.initials: K
authors.lastname: Lam
authors.affiliation: †Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.
authors.forename: Conrad
authors.initials: C
authors.lastname: Chan
authors.affiliation: ⊥Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada L8S 4L8.
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D017321:Clinical Trials, Phase I as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007204:Indium / Q000737:chemistry* / Q000378:metabolism; D057054:Molecular Imaging / Q000379:methods; D058990:Molecular Targeted Therapy; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000378:metabolism; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D000068878:Trastuzumab / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007204:Indium; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab