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.

Radiation dosimetry of para-chloro-2-[18F]fluoroethyl-etomidate: a PET tracer for adrenocortical imaging

“…The estimation of total organ activity based on scaling of reference phantom organ masses by body weight in relation to the reference phantoms is an additional source of uncertainty. Definition of VOIs comprising whole organs, as recommended in the recent EANM guidance on dosimetry for first-in-human studies [ 21 ], would avoid the need for scaling to obtain total organ activities. However, whole-organ VOIs suffer from partial volume effects, are often not feasible because entire organs are not within the field of view during dynamic scans, and, when drawn on CT images, may be inaccurate due to for example respiratory motion-related PET/CT misalignment.…”