Comparison of I-131 Radioimmunotherapy Tumor Dosimetry: Unit Density Sphere Model Versus Patient-Specific Monte Carlo Calculations

High computational requirements restrict the use of Monte Carlo algorithms for dose estimation in a clinical setting, despite the fact that they are considered more accurate than traditional methods. The goal of this study was to compare mean tumor absorbed dose estimates using the unit density sphere model incorporated in OLINDA with previously reported dose estimates from Monte Carlo simulations using the dose planning method (DPMMC) particle transport algorithm. The dataset (57 tumors, 19 lymphoma patients who underwent SPECT/CT imaging during I-131 radioimmunotherapy) included tumors of varying size, shape, and contrast. OLINDA calculations were first carried out using the baseline tumor volume and residence time from SPECT/CT imaging during 6 days post-tracer and 8 days post-therapy. Next, the OLINDA calculation was split over multiple time periods and summed to get the total dose, which accounted for the changes in tumor size. Results from the second calculation were compared with results determined by coupling SPECT/CT images with DPM Monte Carlo algorithms. Results from the OLINDA calculation accounting for changes in tumor size were almost always higher (median 22%, range -1%-68%) than the results from OLINDA using the baseline tumor volume because of tumor shrinkage. There was good agreement (median -5%, range -13%-2%) between the OLINDA results and the self-dose component from Monte Carlo calculations, indicating that tumor shape effects are a minor source of error when using the sphere model. However, because the sphere model ignores cross-irradiation, the OLINDA calculation significantly underestimated (median 14%, range 2%-31%) the total tumor absorbed dose compared with Monte Carlo. These results show that when the quantity of interest is the mean tumor absorbed dose, the unit density sphere model is a practical alternative to Monte Carlo for some applications. For applications requiring higher accuracy, computer-intensive Monte Carlo calculation is needed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90433/1/cbr-2E2011-2E0965.pd

Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

PurposeDeoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo.MethodsPET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times.ResultsRenal excretion was common to all three probes. Bone marrow had higher uptake for L: -(18)F-FAC and L: -(18)F-FMAC than (18)F-FAC. Prominent liver uptake was seen in L: -(18)F-FMAC and L: -(18)F-FAC, whereas splenic activity was highest for (18)F-FAC. Muscle uptake was also highest for (18)F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, respectively.ConclusionThe biodistribution of (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe affinities for nucleoside transporters, dCK, and catabolic enzymes such as cytidine deaminase (CDA). Dosimetry demonstrates that all three probes can be used safely to image the deoxyribonucleoside salvage pathway in humans

Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE. NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained