The 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 application in radiopharmaceutical therapy. Theradi onuclide 177 Lu (lutetium) has been proven useful in several targeted radionuclide therapies because of its favorable decay characteristics and the possibility of reliable labeling of biomolecules used for tumor targeting. Initially, 177 Lu was used in a colloidal form for interstitial injections for sterilization of peritumoral lymph nodes (1). A second important clinical application of 177 Lu has been for peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE and other structurally related peptides. The PRRT use in treatment of neuroendocrine tumors (NETs) is motivated by the fact that the carrier peptide, octreotate, shows highaffinity binding to somatostatin receptors, which are overexpressed on the cell surface of many NETs (2-6). Furthermore, 177 Lu has been used in radioimmunotherapy clinical trials to label different kinds of monoclonal antibodies (7-15).There is a growing body of evidence that radionuclide therapy should follow patient-specific planning protocols, similar to those that are being routinely used in external-beam radiation therapy. Recent literature reviews show correlations between absorbed dose and tumor response as well as normal-tissue toxicity (16). Such correlations indicate that treatments should be based on personalized dosimetry, aiming to deliver therapeutically effective absorbed doses to tumors, while keeping doses to organs at risk below the threshold levels for deterministic adverse effects. In clinical PRRT studies, the primary adverse effects have been mainly renal and hematologic toxicities (2,6).Although several studies have reported estimates of absorbed doses (4,7-9,12) for 177 Lu-DOTATATE PRRT and 177 Lu radioimmunotherapy, most of these estimates have been based on planar imaging and conjugate-view activity quantification. Planar imaging, however, is known to have inherent limitations regarding the accuracy of activity quantification (17). As a result, an increasing number of clinical dosimetry protocols currently include 177 Lu SPECT/CT imaging studies (15,(17)(18)(19) because of their superior accuracy. Comparisons of renal dose estimates in 177 Lu-DOTATATE PRRT based on planar imaging and SPECT/CT, for example, have been reported (17,20) and are summarized in Cremonesi et al. (21).This document presents a set of guidelines outlining data acquisition protocols and image reconstruction techniques that are recommended for quantitative 177 Lu SPECT imaging. The guidelines are...

BACKGROUND: 177 Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. METHODS: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. RESULTS: For some patients, the results showed a large difference in calculated kidneyabsorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084-92.

PurposeTo present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED).MethodTreatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 ± 2 Gy (α/β = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 ± 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR).ResultsFifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function.ConclusionsIndividualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3678-4) contains supplementary material, which is available to authorized users.

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time–activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

Molecular radiotherapy (MRT) has demonstrated unique therapeutic advantages in the treatment of an increasing number of cancers. As with other treatment modalities, there is related toxicity to a number of organs at risk. Despite the large number of clinical trials over the past several decades, considerable uncertainties still remain regarding the optimization of this therapeutic approach and one of the vital issues to be answered is whether an absorbed radiation dose-response exists that could be used to guide personalized treatment. There are only limited and sporadic data investigating MRT dosimetry. The determination of dose-effect relationships for MRT has yet to be the explicit aim of a clinical trial. The aim of this article was to collate and discuss the available evidence for an absorbed radiation dose-effect relationships in MRT through a review of published data. Based on a PubMed search, 92 papers were found. Out of 79 studies investigating dosimetry, an absorbed dose-effect correlation was found in 48. The application of radiobiological modelling to clinical data is of increasing importance and the limited published data on absorbed dose-effect relationships based on these models are also reviewed. Based on National Cancer Institute guideline definition, the studies had a moderate or low rate of clinical relevance due to the limited number of studies investigating overall survival and absorbed dose. Nevertheless, the evidence strongly implies a correlation between the absorbed doses delivered and the response and toxicity, indicating that dosimetry-based personalized treatments would improve outcome and increase survival.