[en] The objective of dosimetry in radiopharmaceutical therapy (RPT) is to understand or predict the likely biological consequences of administering a radiopharmaceutical to a patient. In diagnostic nuclear medicine the biological consequence of interest is risk of radiation detriment, which at the absorbed dose levels involved is primarily the risk of developing late occurring effects, like cancer. In RPT the relevant biological end points are toxicity and efficacy. In both cases, radiobiological models are invoked to convert the physical quantity, absorbed dose, into a biological response probability. The radiobiological model used in risk assessment for late stochastic effects (cancer induction) includes radiation and tissue weighting factors, wR and wT, respectively [8.1, 8.2]. These are associated with a ‘reference person’ and are used in conjunction with organ absorbed doses to calculate the effective dose, E. This quantity may be used to compare the cancer risk associated with diagnostic radiopharmaceuticals using lifetime attributable risk tables [8.3]. The weighting factors and lifetime attributable risk values may be thought of as parameters in a model by which absorbed dose, in Gy, is converted to cancer risk. The radiobiological ‘model’ in the diagnostic scenario has been standardized by international regulatory and professional bodies and is, in general, consistently applied throughout the world for radiation protection [8.4]. In RPT, such standardization of dose‑response modelling has not taken place yet. RPT is becoming more widely implemented and efforts to optimize such treatment using dosimetry based treatment planning [8.5] will require standardized dosimetry methods and standardized or ‘reference’ radiobiological models that are, in a sense, analogous to the ‘reference person’ concept applied in cancer risk evaluation. Continuing the analogy, reference radiobiological models will not predict efficacy and toxicity in an individual patient but would allow biologically based treatment optimization and comparison of therapeutic agents and treatment strategies.

[en] The high data transmission rates required for rapid image transfer have kept separate the development of PACS and of patient information management systems (PIMS). The resulting dual system requires separate entry of patient data in the PIMS and also in the PACS. The authors are designing a combined Information Management and Picture Archive and Communication System (IMPACS) for nuclear medicine which should result in substantial cost savings. Each PC is part of a PC-based network on which the PIMS runs. Ethernet image transmission (from each camera to an image processing computer) permits quantitation (up to 512 x 512 x 8 bits), while image review transmission is by video (CATV). On-line archiving is on a (2 GB) optical laser disk. Image review requests occur within the PIMS;images are ''grabbed'' locally using a (512 x 512 x 8 bit) frame grabber. A first-order cost estimate of a currently implementable system (Ethernet links initially replaced by floppy disk) is $77,400 (ImageFile, Sudbury Systems, Inc.) plus $20,000 per image review work station (IBM-AT with frame grabber)

[en] Clinical dosimetry is a multistep procedure (see Fig. 11.1); each step is essential to obtain an accurate estimate of the absorbed dose delivered to one or more tumours or normal tissues. The first step in the clinical dosimetry workflow is the calibration procedure (step 1). This is a prerequisite for activity determination and may require phantom image acquisition with a known amount of activity that should ideally be traceable to a standard laboratory. Procedures for obtaining quantitative information on the activity or activity concentration from images were presented in Chapter 4 and will include sensitivity determination and may include partial volume and dead time corrections. The calibration procedure is a key step in accurately determining the activity distribution. The calibration step and patient image/data acquisition step (step 2) are linked; the camera settings used in the quantitative imaging calibration procedure should be used for all patient imaging. For single photon emission computed tomography (SPECT) quantitative imaging this may mean that the acquisition matrix size, the type of collimator or the number and position of energy windows should remain constant between phantom calibration and patient imaging.

[en] Radiopharmaceutical therapy (RPT) may be broadly defined as the use of radionuclides to deliver lethal radiation to tumour cells or other cells that are not functioning normally, such as those of the thyroid gland. In contrast to brachytherapy, in which radiation delivery is controlled by implantation of radionuclides that are sealed in seeds or capsules intended to avoid release of the radionuclide, radiation delivery in RPT involves the use of pharmaceuticals that either bind specifically to tumours or that accumulate by means of a broad array of physiologic mechanisms. In patients who are ineligible for chemo‑refractory and external beam radiation therapy (EBRT), RPT offers viable treatment options where none otherwise exist. RPT has yielded durable responses in heavily pretreated, refractory populations [1.1–1.5]. In castrate‑resistant metastatic prostate cancer, RPT with the alpha emitter ²²³Ra has yielded significantly increased survival rates in patients previously considered untreatable [1.6–1.10]. Similarly, promising results have been observed in adult acute myelogenous leukaemia patients treated with antibody‑conjugated ²²⁵Ac, also an alpha‑ particle emitter [1.11–1.13]. In Europe, RPT using radiolabelled peptides has demonstrated efficacy in patients with late‑stage, neuroendocrine tumours (NETs).

[en] Full text of publication follows. Objectives: 3-dimensional dosimetry offers a number of specific advantages in terms of personalizing radiopharmaceutical therapy (RPT). Modern imaging modalities such as SPECT and PET, acquired at multiple time points after administration of pre-therapeutic activity, provide the data necessary for the 3-dimensional absorbed dose maps and subsequent personalized treatment planning. As such, any limitation of the imaging data, in particular the resolution, will inhibit the dosimetry. Geometric modeling can play an important role in complementing patient imaging and provide reliable personalized dosimetry. Methods: we illustrate this concept with several examples: (1) arterial wall dosimetry in 131-tositumomab therapy of non-Hodgkin's lymphoma, (2) salivary gland dosimetry in "1"3"1I therapy of thyroid cancer, and (3) renal toxicity from "2"2"5Ac therapy of metastatic breast cancer in a pre-clinical model. In each example, a geometrical model within the GEANT4 framework was created and Monte Carlo simulation was run to create S-values for the different compartments. Using imaging data acquired from the individual patient (or mouse), these S-values were then used to provide patient-specific dosimetric results. Results: absorbed doses were calculated in each example. For the arterial wall dosimetry, this led to the conclusion that for myelo-ablative regimes of RPT, the artery walls should be considered as potentially dose-limiting. For "1"3"1I salivary gland and renal alpha-particle modeling, this led to the result that localization of activity uptake is likely responsible for the discrepancies between calculated whole organ absorbed dose and observed toxicities. Conclusions: modeling is an important component in the progression of science, and is part of the interplay between theory and experiment. In the realm of personalized dosimetry, modeling can play a key role providing insight into absorbed dose to regions of interest smaller than the imaging resolution. (authors)

[en] Full text of publication follows. Objectives: combination therapy is a hallmark of successful cancer therapy. Patient-specific optimization of treatment using dosimetry based on pre-therapeutic images is a fundamental strength of radiopharmaceutical therapy. To date, attempts to combine radiopharmaceuticals, either with other radiopharmaceuticals or with other treatment modalities have been made largely on an empirical basis, without the dosimetric framework necessary for patient-specific optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted RPT-RPT and combined RPT-external beam radiation therapies (XRT). Methods: the range of potential administered activities (AA) or external beam monitor units is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined treatments. For combined RPT, illustrated for "1"3"1I-tositumomab (Bexxar) and "9"0Yibritumomab tiuxetan (Zevalin) therapy of non-Hodgkin's lymphoma, the limiting normal organ constraints are plotted as a function of the AAs and the optimal combination of activities is obtained by calculating the tumor BED along those normal organ MTBED limits. For combined "1"5"3Sm-EDTMP RPT-XRT treatment of osteosarcoma, the biological effective dose (BED) was used to translate voxelized RPT absorbed dose values into an equivalent two-Gray-fraction XRT absorbed dose (EQD2) map and thereafter enabling combined treatment planning. Results: in the case of RPT-RPT therapy, the tumor BED optimization results were calculated and plotted as a function of AA using patient normal organ kinetics for the two radiopharmaceuticals. A treatment plan for combined RPT-XRT was designed which would deliver a tumoricidal dose while delivering no more than 50 Gy of EQD2 to the spinal cord of a patient with a para-spinal tumor. Conclusions: Rational, dosimetry-based approaches for combination therapies involving RPT have been developed within the framework of a proven 3-dimensional personalized dosimetry software, 3D-RD. Clinical trials based on these methodologies are currently being developed. (authors)

[en] A multicompartment zinc model was used to calculate cumulated activities for zinc-63 (T 1/2 = 38.1 m) and zinc-65 (T 1/2 = 244.1 d) given by intravenous (IV), oral and jejunum (enteral tube) administration routes. The model dramatically facilitates such calculations since only the initial conditions are changed. The cumulated activities were obtained for 8 anatomically defined regions by appropriate combinations of model compartments. Because the ovaries are especially important for risk assessment and were not resolved by the model, the 11 day liver-to-ovary ratio and the model derived total-body kinetics were assumed. The power of a model approach to radiation dosimetry is brought out very clearly by inspection of the Zn-63 results for stomach wall which show variations for route of administration from 1 to 3 mrads/mCi Zn-63 for IV or tube administration to 2.7 rads for oral administration. The dose to the liver drops from 500 mrads fo IV administration to 140 mrads by tube and 100 mrads orally. Gonad (24-31 mrads) and average body doses (26 mrads) are similar to each other and as would be expected show little variation with route of administration. The ability to estimate radiation doses to the region of the jejunum prior to any such experiments is illustrated by this work

No abstract available

[en] The increased interest in alpha-particle emitter radiopharmaceutical therapy (αRPT) requires: (1) a re-examination of the strategies used to conduct phase 1 trials as the current administered activity (AA)-based RPT leads to conservative treatment that, typically, prevents normal organ toxicity but at the expense of tumor control; (2) the imaging information should be at an anatomical scale that is relevant to the dimensions of the target tissue, the emission length and the spatial distribution of the RPT; and 3) reliable radiobiological models are required to translate dosimetric information into tumor response or normal organ toxicity

[en] Estimates of radiation absorbed dose have been determined for the steady-state distribution of oxygen-15 (T1/2 . 122 sec) from inhalation of molecular oxygen, ¹⁵O₂; carbon dioxide, C¹⁵O₂; and carbon monoxide, C¹⁵O. Biodistribution data for ¹⁵O-labeled water, produced by the metabolism of oxygen and from CO₂ by pulmonary carbonic anhydrase, were used. Lung gas and intravascular activities are also included. The total oxygen utilized was taken to be 14.4 l/hr. Seventeen tissues were included as source organs. The radiation dose is directly proportional to the duration of inhalation. Air containing a constant level of ¹⁵O is provided in excess of need to the patient, who breathes under his own control. The lung, which is known to be a particularly radiosensitive tissue, appears to be the dose-limiting or critical tissue. The radiation dose estimates for lung, based upon 1 hr of breathing air with an activity concentration of 1 mCi/l, are 3.6, 1.2, and 2.8 rads, respectively, for ₁₅O₂, C₁₅O₂, and C₁₅O