EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials

Abstract

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents. The guideline includes a short introduction to different emitters and carrier molecules, followed by recommendations on the methods for activity measurement, pharmacokinetic analyses, as well as absorbed dose calculations and uncertainty analyses. The optimal use of preclinical information and studies involving diagnostic analogues is discussed. Good practice reporting is emphasised, and relevant dosimetry parameters and method descriptions to be included are listed. Three examples of first-in-human dosimetry studies, both for diagnostic tracers and radionuclide therapies, are given.

Keywords: Dosimetry; European Association of Nuclear Medicine; First-in-human; Nuclear medicine; Radiopharmaceuticals.

Fig. 1

The number of phase 1 or early phase 1 interventional studies with therapeutic radionuclides and molecular or functional targeting mechanisms recorded in ClinicalTrials.gov per year, as of end of 2022. Electron emitters and alpha emitters are split in (a) and (b), and in (c), the results have been separated according to carrier instead of emitter

Fig. 2

The number of publications with the Mesh terms “Pilot Projects” and “Radionuclide Imaging” and mention of the individual radionuclides in the title or abstract, as of end of 2022. The 1252 nuclides from ICRP 107 were included in the search, and radionuclides used unambiguously for therapy have been removed. a Emitters primarily used for PET imaging and b single photon emitters. c The hits separated by carrier

Fig. 3

Flow chart for designing and updating the measurement protocol