The contest between internal and external-beam dosimetry: The Zeno's paradox of Achilles and the tortoise.

Radionuclide therapy, also called molecular radiotherapy (MRT), has come of age, with several novel radiopharmaceuticals being approved for clinical use or under development in the last decade. External beam radiotherapy (EBRT) is a well-established treatment modality, with about half of all oncologic patients expected to receive at least one external radiation treatment over their disease course. The efficacy and the toxicity of both types of treatment rely on the interaction of radiation with biological tissues. Dosimetry played a fundamental role in the scientific and technological evolution of EBRT, and absorbed doses to the target and to the organs at risk are calculated on a routine basis. In contrast, in MRT the usefulness of internal dosimetry has long been questioned, and a structured path to include absorbed dose calculation is missing. However, following a similar route of development as EBRT, MRT treatments could probably be optimized in a significant proportion of patients, likely based on dosimetry and radiobiology. In the present paper we describe the differences and the similarities between internal and external-beam dosimetry in the context of radiation treatments, and we retrace the main stages of their development over the last decades

Inter-comparison of quantitative imaging of lutetium-177 (177Lu) in European hospitals

Background: This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. Results: The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. Conclusions: A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods

3-D Image-Based Dosimetry in Radionuclide Therapy

Radionuclide therapy is the use of radioactive drugs for internal radiotherapy, mainly for the treatment of metastatic disease. As opposed to systemic cancer therapies in general, the use of radioactively labeled drugs results not only in a targeted therapy but also the possibility of imaging the distribution of the drug during therapy. From such images, the absorbed doses delivered to tumors and organs at risk can be calculated. Calculation of the absorbed dose from 3-D images such as single-photon emission computed tomography (SPECT)/CT, and in some cases positron emission tomography (PET)/CT, relies on image-based activity quantification. Quantification is accomplished by modeling the physics involved in the image-formation process, and applying image-processing methods. From a time-sequence of such quantitative images, the absorbed doses are then calculated. Although individual-patient dosimetry is a standard component of other forms of radiotherapy, it is still overlooked in the majority of radionuclide therapies. In this review, we summarize the physical and technical problems that need to be addressed in image-based dosimetry. The focus is on SPECT, since most of the radionuclides used are single-photon emitters, although the use of PET is also discussed. Practical issues of relevance for the practical implementation of personalized dosimetry in radionuclide therapy are also highlighted

Peptide Receptor Radionuclide Therapy – Prospects for Personalised Treatment

Peptide receptor radionuclide therapy is a type of molecular radiotherapy that has been used in the treatment of patients with neuroendocrine tumours for over two decades. It is not until recently, however, that it has achieved regulatory approval. The currently approved treatment regimen is a one-size-fits-all scheme, i.e. all patients receive a fixed activity of the radiopharmaceutical (177Lu-DOTATATE) and a fixed number of treatment cycles. Several research groups around the world have studied different approaches of further improving on the results of peptide receptor radionuclide therapy, with many promising retrospective and prospective clinical studies having been published over the years. In this overview, we summarise some of the most promising strategies identified so far

A method for tumor dosimetry based on hybrid planar-SPECT/CT images and semiautomatic segmentation

Purpose: A hybrid planar-SPECT/CT method for tumor dosimetry in 177Lu-DOTATATE therapy, applicable to datasets consisting of multiple conjugate-view images and one SPECT/CT, is developed and evaluated. Methods: The imaging protocol includes conjugate-view imaging at 1, 24, 96, and 168 h post infusion (p.i.) and a SPECT/CT acquisition 24 h p.i. The dosimetry method uses the planar images to estimate the shape of the time–activity concentration curve, which is then rescaled to absolute units using the SPECT-derived activity concentration. The resulting time-integrated activity concentration coefficient (TIACC) is used to calculate the tumor-absorbed dose. Semiautomatic segmentation techniques are applied for tumor delineation in both planar and SPECT images, where the planar image segmentation is accomplished using an active-rays-based technique. The selection of tumors is done by visual inspection of planar and SPECT images and applying a set of criteria concerning the tumor visibility and possible interference from superimposed activity uptakes in the planar images. Five different strategies for determining values from planar regions of interest (ROIs), based on entire or partial ROIs, and with and without background correction, are evaluated. Evaluation is performed against a SPECT/CT-based method on data from six patients where sequential conjugate-view and SPECT/CT imaging have been performed in parallel and against ground truths in Monte Carlo simulated images. The patient data are also used to evaluate the interoperator variability and to assess the validity of the developed criteria for tumor selection. Results: For patient images, the hybrid method produces TIACCs that are on average 6% below those of the SPECT/CT only method, with standard deviations for the relative TIACC differences of 8%–11%. Simulations show that the hybrid and SPECT-based methods estimate the TIACCs to within approximately 10% for tumors larger than around 10 ml, while for smaller tumors, all methods underestimate the TIACCs due to underestimations of the activity concentrations in the SPECT images. The planar image segmentation has a low operator dependence, with a median Dice similarity coefficient of 0.97 between operators. The adopted criteria for tumor selection manage to discriminate the tumors for which the absorbed-dose deviations between the hybrid and SPECT methods are the highest. Conclusions: The hybrid method is found suitable for studies of tumor-absorbed doses in radionuclide therapy, provided that selection criteria regarding the visibility and overlapping activities in the planar images are applied

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT applied for Dosimetry of Radiopharmaceutical Therapy.

Accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet No. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177-Lu (Lutetium) and its main application in radiopharmaceutical therapy

Dosimetry in patients with B-cell lymphoma treated with [90Y]ibritumomab tiuxetan or [131I]tositumomab.

Radioimmunotherapy involves the use of radiolabeled monoclonal antibodies (MAbs) to treat malignancy. The therapeutic effect is determined by the radiopharmaceutical, the radiation absorbed dose and previous treatments. There are currently two approved radiopharmaceuticals for the treatment of B-cell lymphoma - the 90Y-labeled ibritumomab and the 131I-labeled tositumomab. Both are directed against CD20, albeit not against the same epitope. This paper summarizes current results of dose-responses for normal tissues and tumours of [131I]tositumomab and [90Y]ibritumomab tiuxetan, discusses them in the context of dosimetry methods used and highlights the assumptions being made in the different dosimetry methodologies. Moreover, we wish to point at the possibility of performing low-cost therapy bremsstrahlung imaging for [90Y]ibritumomab tiuxetan to confirm biodistribution, and possibly also for dosimetric calculations