Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray"

Abstract

Introduction: Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy.

Review: This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce.

Developments: In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.

Fig. 1

Tumour dose-response relationship in 13 patients treated with ⁹⁰Y-DOTATOC. Tumour volumes were assessed by CT before and after treatment. Tumour dose estimates were derived from CT scan volume measurements and quantitative ⁸⁶Y-DOTATOC imaging performed before treatment. Data were further computed using the MIRDOSE spherical model. Reprinted by permission of the Society of Nuclear Medicine from [63]