Clinical radionuclide therapy dosimetry: the quest for the “Holy Gray”

Abstract

IntroductionRadionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy.ReviewThis 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.DevelopmentsIn 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.

Influence of Vitamin C on Salivary Absorbed Dose of 131I in Thyroid Cancer Patients: A Prospective, Randomized, Single-Blind, Controlled Trial

“…Salivary parenchymal functions and symptoms after 131 I therapy were not studied. Although it is accepted that radiation-absorbed dose to normal tissue in radionuclide therapy is able to predict toxicity (17)(18)(19), investigations of the dose-effect relation for the salivary glands in 131 I therapy remain essential. Second, we investigated the effect of only the timing of salivary gland stimulation, and if the sour prescription in the study had been less stringent, the study would have been insufficiently powerful to detect the effect of sour stimulation on salivary absorbed dose.…”

“…As is well recognized, normal-tissue radiation-absorbed dose delivered by an administered radiopharmaceutical correlates with attendant tissue toxicity (17)(18)(19). Dosimetry is thus important both for determining the limit beyond which administered radiation would cause harmful side effects and for enabling assessment of the effects of various protective measures.…”

“…Calculation of salivary absorbed dose was based on the MIRD schema of the Society of Nuclear Medicine. Results: Seventytwo patients (18,18,19, and 17 patients from groups A, B, C, and D, respectively) were eligible for the analysis of salivary dosimetry. Differences in absorbed doses to the parotid salivary gland (0.18 6 0.11, 0.16 6 0.07, 0.16 6 0.09, and 0.16 6 0.12 mGy/MBq in groups A, B, C, and D, respectively; P 5 0.37) and submandibular salivary gland (0.19 6 0.05, 0.17 6 0.05, 0.18 6 0.07, and 0.17 6 0.06 mGy/MBq, respectively; P 5 0.28) were not statistically significant among groups.…”

4-Step Renal Dosimetry Dependent on Cortex Geometry Applied to 90Y Peptide Receptor Radiotherapy: Evaluation Using a Fillable Kidney Phantom Imaged by 90Y PET

“…Assessment of the absorbed doses in the target and critical tissues is also needed to optimize the activity to inject (5)(6)(7)(8)(9). Until recently, investigators focused on the major emission of 90 Y (i.e., b-rays) that was imaged with SPECT using the bremsstrahlung x-rays, the energy spectrum of which is continuous.…”

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…A recent review by the EANM Dosimetry Committee identified 48 papers (out of 79 surveyed) employing the use of radionuclide dosimetry showing a strong correlation between absorbed dose and the tumour response & toxicity over a wide range of radionuclide treatments (including 90 Y-RE) [9], and many works have noted the lack of randomized trials comparing dosimetry-based radionuclide therapy to fixed dosing, or dosing per kg body weight [10,11]. For routine use, there is a requirement of standardized procedures for absorbed dose calculations [12] and improved reliability of radiobiological models used to convert dosimetric data to biologic endpoints [13].…”