Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples.

Petra Kolenc Peitl,Clemens Decristoforo,Paola Erba,Piotr Garnuszek,Renata Mikolajczak,Christine Rangger,Alicja Hubalewska‐Dydejczyk,Theodosia Maina

doi:10.1002/jlcr.3712

Abstract

With the development of ever more radiopharmaceuticals suitable for theranostic applications, translation of novel compounds from the preclinical stage towards clinical application becomes a bottleneck for the advances in Nuclear Medicine. This review article summarizes the current regulatory framework for clinical trials with radiopharmaceuticals in the European Union, provides a general overview of the documentation required, and addresses quality, safety, and clinical aspects to be considered. By using a recent successful example of translating a theranostic peptide radioligand, namely 111In‐CP04, which targets receptors expressed in medullary thyroid carcinoma, the pathway from the preclinical development over establishing the required pharmaceutical documentation to designing and submitting a clinical trial is reviewed. Details regarding preclinical data, generation of the documentation, and final successful application are described. This article should provide an insight in an ever more complex process to bring innovations in the field of radiopharmaceuticals into patients.

Highlights

The concept of combining imaging properties with the therapeutic potential of decaying radionuclides in an integrated theranostic concept has received a tremendous spin within the last years.[1]
The documents differentiate the chemical and pharmaceutical information package (Quality) from the nonclinical and clinical safety and efficacy information, including toxicology and pharmacology of the new radiopharmaceutical. This differentiation in particular is important for radiopharmaceuticals; specific guidance has been released by the EANM to provide information on how an Investigational Medicinal Product Dossier (IMPD) for a radiopharmaceutical can be designed and is a very useful reference when coping with this task.[18]
The translation of new theranostic radiopharmaceuticals requires clinical trials, which are heavily regulated within the EU, and in most countries worldwide

Summary

SPECIAL ISSUE ARTICLE

Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples. With the development of ever more radiopharmaceuticals suitable for theranostic applications, translation of novel compounds from the preclinical stage towards clinical application becomes a bottleneck for the advances in Nuclear Medicine. This review article summarizes the current regulatory framework for clinical trials with radiopharmaceuticals in the European Union, provides a general overview of the documentation required, and addresses quality, safety, and clinical aspects to be considered. By using a recent successful example of translating a theranostic peptide radioligand, namely 111In‐CP04, which targets receptors expressed in medullary thyroid carcinoma, the pathway from the preclinical development over establishing the required pharmaceutical documentation to designing and submitting a clinical trial is reviewed. KEYWORDS 111In‐CP04, clinical trial, peptide radiopharmaceuticals, regulatory framework, theranostics nuclear medicine

| INTRODUCTION

Analytical control Stability

Acute toxicity Extended single dose toxicity

| CONCLUSION