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In the last few years there has been an increasing interest in the measurement of the absorbed dose from radionuclides, with special attention devoted to molecular radiotherapy treatments. In particular, the determination of the absorbed dose from beta emitting radionuclides in liquid solution poses a number of issues when dose measurements are performed using thermoluminescent dosimeters (TLD). Finite volume effect, i.e. the exclusion of radioactivity from the volume occupied by the TLD is one of these. Furthermore, TLDs need to be encapsulated into some kind of waterproof envelope that unavoidably contributes to beta particle attenuation during the measurement. The purpose of this study is twofold: I) to measure the absorbed dose to water, D w , using LiF:Mg,Cu,P chips inside a PMMA cylindrical phantom filled with a homogenous 90YCl3 aqueous solution II) to assess the uncertainty budget related to D w measurements. To this purpose, six cylindrical PMMA phantoms were manufactured at ENEA. Each phantom can host a waterproof PMMA stick containing 3 TLD chips encapsulated by a polystyrene envelope. The cylindrical phantoms were manufactured so that the radioactive liquid environment surrounds the whole stick. Finally, D w measurements were compared with Monte Carlo (MC) calculations. The measurement of absorbed dose to water from 90YCl3 radionuclide solution using LiF:Mg,Cu,P TLDs turned out to be a viable technique, provided that all necessary correction factors are applied. Using this method, a relative combined standard uncertainty in the range 3.1–3.7% was obtained on each D w measurement. The major source of uncertainty was shown to be TLDs calibration, with associated uncertainties in the range 0.7–2.2%. Comparison of measured and MC-calculated absorbed dose per emitted beta particle provided good results, with the two quantities being in the ratio 1.08.

Purpose To assess the capability of different types of detectors to measure relative output factors (OF) at high dose per pulse by comparison with alanine dosimeters, which are independent of dose rate. Methods Measurements were made in 9 MeV and 7 MeV electron beams produced by a Novac7 accelerator for intraoperative radiotherapy. Applicators with diameter of 10-7-6-5 and 4 cm were used. The dose per pulse varied from about 30 mGy, for the 10 cm reference applicator, to about 70 mGy, for the 4 cm applicator. Five types of plane-parallel ionization chambers (PTW Advanced Markus, Markus and Roos, IBA PPC40 and PPC05), two types of silicon diodes (PTW 60017 and IBA EFD3G) and a PTW 60019 microDiamond were considered. For the ionization chambers, correction factors for ion recombination effects were determined for each applicator using a modified two-voltage-analysis method that includes the free-electron component. Results Reference OF values were determined by alanine dosimeters with a standard combined uncertainty of 0.8%. Deviations from the reference OFs were generally within 1.5% for all the detectors, hence within the 95% confidence interval of alanine measurements. Larger deviations of up to about 2% obtained in a few cases are consistent with a 0.7% long-term reproducibility of OF measurements. Conclusions Comparison with alanine measurements demonstrated that all the detectors considered in this work can be used to measure OFs in high dose-per-pulse electron beams with an accuracy better than 2%, provided that appropriate corrections for ion recombination effects are applied when using ionization chambers.

It is generally acknowledged that calibration of the imaging system (be it a SPECT or a PET scanner) is one of the critical components associated with in vivo activity quantification in nuclear medicine. The system calibration is generally performed through the acquisition of a source with a known amount of radioactivity. The decay-corrected calibration factor is the "output" quantity in a measurement model for the process. This quantity is a function of a number of "input" variables, including total counts in the volume of interest (VOI), radionuclide activity concentration, source volume, acquisition duration, radionuclide half-life, and calibration time of the radionuclide. Uncertainties in the input variables propagate through the calculation to the "combined" uncertainty in the output quantity. In the present study, using the general formula given in the GUM (Guide to the Expression of Uncertainty in Measurement) for aggregating uncertainty components, we derive a practical relation to assess the combined standard uncertainty for the calibration factor of an emission tomography system. At a time of increasing need for accuracy in quantification studies, the proposed approach has the potential to be easily implemented in clinical practice. © 2017 Marco D'Arienzo and Maurice Cox.

Purpose Radioembolization (RE) with 90Y-microspheres is a well-established treatment modality for treating liver malignancies. At a time of increasing evidence for dose–effect relationships in RE with 90Y microspheres [1] , [2] , the general consensus is that there is an urgent need for accurate dosimetry in patients undergoing RE treatment. This work aimed at estimating absorbed doses to lesions and normal liver in a novel anthropomorphic set-up. Methods AbdoMan is a 3D-printed phantom provided with a fillable liver section and multiple inserts for lesion representation. A SPECT/CT Symbia Intevo provided with the proprietary xSPECT quantitative software was used to image the phantom according to the acquisition protocol currently used for RE patients. Specific regions of interest (ROIs) were drawn on MIM 6.1.7 system. A homemade tool was developed in MATLAB for image analysis and dose calculation based on two methods: I) convolution kernel and II) local deposition method. The accuracy of the two different dosimetric methods was evaluated by comparing dose-rate volume histograms (DrVHs). Moreover, γ -index was used to compare the dose distributions obtained by the two activity-to-dose methods. Results Differences calculated by the 3D γ -index are within 2%-2 mm for all AbdoMan inserts. The dose-kernel results in a γ γ as well as several image artefacts. In particular, an apparent over-dosage (about 25%) was observed in inserts with larger diameter, most likely due to spill-in and spill-out phenomena. The DrVHs for considered ROIs are within 2%-2 mm for both methods. Conclusions In RE treatment planning the dose-kernel method proved to be more accurate with respect to deposition method based on full 3D dose distributions.

Objective: To assess the impact of nonuniform dose distribution within lesions and tumor-involved organs of patients receiving Zevalin®, and to discuss possible implications of equivalent uniform biological effective doses (EU-BED) on treatment efficacy and toxicity. MATLAB™ -based software for voxel-based dosimetry was adopted for this purpose. Methods: Eleven lesions from seven patients with either indolent or aggressive non-Hodgkin lymphoma were analyzed, along with four organs with disease. Absorbed doses were estimated by a direct integration of single-voxel kinetic data from serial tomographic images. After proper corrections, differential BED distributions and surviving cell fractions were estimated, allowing for the calculation of EU-BED. To quantify dose uniformity in each target area, a heterogeneity index was defined. Results: Average doses were below those prescribed by conventional radiotherapy to eradicate lymphoma lesions. Dose heterogeneity and effect on tumor control varied among lesions, with no apparent relation to tumor mass. Although radiation doses to involved organs were safe, unexpected liver toxicity occurred in one patient who presented with a pattern of diffuse infiltration. Conclusion: Voxel-based dosimetry and radiobiologic modeling can be successfully applied to lesions and tumor-involved organs, representing a methodological advance over estimation of mean absorbed doses. However, effects on tumor control and organ toxicity still cannot be easily predicted. © Copyright 2013, Mary Ann Liebert, Inc.

OBJECTIVES The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a β+–β- emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. METHODS Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation–maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose–volume histograms. RESULTS Dosimetry studies carried out on the body phantom with ordered subset expectation–maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. CONCLUSION According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography.Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors.With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75.90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

Purpose Radioembolization (RE) with 90Y-microspheres has gained widespread acceptance as a safe and effective technique for treating liver malignancies. Accurate quantification in RE is a key step in treatment planning optimization and it is becoming a pressing issue in the light of the Directive 2013/59/EURATOM, stating that individual dose planning must be enforced in legislation by EU member states by February 2018. The aim of this study was to develop a SPECT/CT imaging protocol for quantitative imaging optimization in RE based on a novel anthropomorphic 3D-printed phantom. Methods and materials A SPECT/CT system provided with a novel software for imaging quantification was used to assess the quantitative accuracy of 99mTc-MAA SPECT imaging for treatment planning in RE. Gamma camera calibration factors and recovery coefficients were determined performing preliminary SPECT/CT acquisitions of a homogeneous and a NEMA/IEC phantom, respectively. The quantification procedure was then validated using a 3D-printed anthropomorphic phantom provided with a fillable liver section and multiple inserts. Raw data reconstruction was performed using two independent software: i) the built-in xSPECT package, using both the Ordered Subset Expectation–Maximization (OSEM) and the Ordered Subset Conjugated Gradient (OSCG) algorithm; ii) the commercially available QSPECT software based on OSEM method. All reconstructed images were manually fused and appropriate regions of interest (ROIs) were drawn on the MIM 6.1.7 system. Results The measured activity concentration is consistent within 3% with the expected activity concentration values. This is in keeping with the overall accuracy ( 10%) stated by the manufacturer. No substantial differences were reported between xSPECT with OSCG or OSEM in terms of relative activity. However, a 20% difference was found between ROIs extracted from images reconstructed with xSPECT and QSPECT using OSEM. Several artifacts were visible in the QSPECT reconstruction, likely due to the limited area used for attenuation and scatter corrections within the software. Conclusions The investigated protocol based on the innovative xSPECT tool allows an accurate absolute quantification within 3%. QSPECT software provides the poorest results with several artifacts as well as intrinsic dishomogeneities.

Purpose The high dose per pulse of electron beams produced by some mobile accelerators for intraoperative radiotherapy can affect output factor (OF) measurements, since the dose rate increases by a factor larger than two from the reference to the smallest radiation field. Aim of this work was to assess the capability of different types of detectors to measure OFs at high dose per pulse by comparison with alanine dosimeters, which are independent of dose rate. Methods Measurements were made in 9 and 7 MeV electron beams produced by a Novac 7 accelerator. PMMA cylindrical applicators with diameter of 100 mm (reference field), 70 mm, 60 mm, 50 mm and 40 mm were used. The dose per pulse varied from about 30 mGy, for the 100 mm applicator, to about 70 mGy, for the 40 mm applicator. OFs were determined using four types of plane-parallel ionization chambers (PTW Advanced Markus and Roos, IBA PPC40 and PPC05), two types of silicon diodes (PTW 60017 and IBA 3FG-3D), a PTW microDiamond and alanine dosimeters. Ionization chamber signals were corrected for ion recombination effects using a modified two-voltage-analysis method that includes the free-electron component. Results A fairly good agreement was found between OFs measured by the three types of solid-state detectors and those measured by alanine. Differences were generally below 1% and maximum discrepancies around 2%. For the Advanced Markus and the PPC05 chambers differences from alanine results were below 1.7%. For the Roos and the PPC40 chambers agreement with alanine was within 2.3% down to the 50 mm applicator, while differences of several percent were found for the smallest applicator, most likely due to volume averaging effect. The variation of ion recombination correction factor with field size was below 1% for the Advanced Markus and the PPC05 chambers and up to about 10% for the Roos and the PPC40 chambers. Conclusions Comparison with alanine measurements demonstrated that all the detectors considered in this work can be used to measure OFs in high-dose-per-pulse electron beams with an accuracy of 2%, provided that appropriate corrections for ion recombination effects are applied when using ionization chambers.

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with 90Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long 90Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a 18F-FDG PET 6 months after the treatment. At 90Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at 90Y PET. According to our experience, the use of 90Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases. © 2013 The Japanese Society of Nuclear Medicine.

Background: Fluorodeoxygluose (FDG) positron emission/computed tomography (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal carcinomatosis (PC). In this study, we assessed whether dual-time point imaging can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal cancer (CRC). Methods: Thirty-nine patients with past history of CRC were evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If one or more focal areas of increased FDG uptake (standardized uptake value, SUV max>2.5) were found in the abdomen, 1 L of carbonated water was orally administered to patients and a delayed scan of the abdominal region was acquired at 2 hours. The SUV max and the mean Delta (Δ) SUV were calculated. The scintigraphic results were compared with the results of colonoscopy and histology and with the clinical follow-up. Results: Thirteen out of the 39 patients did not show any significant area of FDG uptake at the whole-body scan. The remaining 26 patients showed an overall number of 27 sites of focal increased uptake, showing a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11 cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall number of 16 sites) with SUV max of 15.6+4 and mean Δ SUV of +26.3%±7.5%. In these cases, final diagnosis was PC in 10 patients (according to cytology or histology) and dysplastic polyp in 5 cases. No significant difference in Δ SUV was found between patients with PC and those with polypoid formations. Conclusions: According to our results, dual-time point imaging after carbonated water may increase the accuracy of FDG PET/CT for the imaging of PC in patients affected by CRC. © Mary Ann Liebert, Inc.

Aim of the present article was to perform three-dimensional (3D) single photon emission tomography-based dosimetry in radioimmunotherapy (RIT) with (90)Y-ibritumomab-tiuxetan. A custom MATLAB-based code was used to elaborate 3D images and to compare average 3D doses to lesions and to organs at risk (OARs) with those obtained with planar (2D) dosimetry. Our 3D dosimetry procedure was validated through preliminary phantom studies using a body phantom consisting of a lung insert and six spheres with various sizes. In phantom study, the accuracy of dose determination of our imaging protocol decreased when the object volume decreased below 5 mL, approximately. The poorest results were obtained for the 2.58 mL and 1.30 mL spheres where the dose error evaluated on corrected images with regard to the theoretical dose value was -12.97% and -18.69%, respectively. Our 3D dosimetry protocol was subsequently applied on four patients before RIT with (90)Y-ibritumomab-tiuxetan for a total of 5 lesions and 4 OARs (2 livers, 2 spleens). In patient study, without the implementation of volume recovery technique, tumor absorbed doses calculated with the voxel-based approach were systematically lower than those calculated with the planar protocol, with average underestimation of -39% (range from -13.1% to -62.7%). After volume recovery, dose differences reduce significantly, with average deviation of -14.2% (range from -38.7.4% to +3.4%, 1 overestimation, 4 underestimations). Organ dosimetry in one case overestimated, in the other underestimated the dose delivered to liver and spleen. However, both for 2D and 3D approach, absorbed doses to organs per unit administered activity are comparable with most recent literature findings.

Terahertz (THz) frequencies are found in a previously underexploited region of the radiation spectrum. This non-ionising energy is now being employed in medical imaging, so the possibility of adverse effects on human skin was evaluated. Primary cultures of normal human keratinocytes (NHKs) express adhesion molecules that comprise part of the natural barrier function of the skin. The effects of exogenous agents on this barrier function can be measured. The ND7/23 cell line, which displays the characteristics of sensory neurones, can proliferate in the undifferentiated state, but can be induced to differentiate and develop neurite-like projections. Previous studies with NHK and neural cell cultures produced no evidence of the inability of these cells to differentiate and form a barrier following THz exposure. The cells were exposed to 0.14THz radiation for times varying from 10 minutes to 24 hours. For each 80-nanosecond pulse, the cells were exposed to a peak power of between 24 and 62mW/cm2, i.e. a total energy at peak power of 345J, or 86J at average power over 24 hours. No changes in cell activity occurred, as monitored with the resazurin reduction assay, or with the barrier function of the human corneal cells, as measured with the fluorescein leakage assay. The monitoring of differentiation by using an assay for cornified envelope formation, revealed no adverse effects. Glutathione (GSH) and heat shock protein 70 levels were examined before and after differentiation, to determine the degree of the stress response, with the effects of UVB radiation as a control. UVB induced a stress response, as did heat shock treatment at 43°C, whilst 0.15THz radiation, even after 24 hours of exposure, did not. Repeated exposure to THz radiation at this level, also resulted in no detectable adverse reactions.

The effects of pulsed 130 GHz radiations on lipid membrane permeability were investigated by using cationic liposomes containing dipalmitoyl phosphatidylcholine (DPPC), cholesterol, and stearylamine. Carbonic anhydrase (CA) was loaded inside the liposomes and the substrate p-nitrophenyl acetate (p-NPA) added in the bulk aqueous phase. Upon permeation across the lipid bilayer, the trapped CA catalyzes the conversion of the p-NPA molecules into products. Because the self-diffusion rate of p-NPA across intact liposomes is very low the CA reaction rate, expressed as Delta A/min, is used to track membrane permeability changes. The effect of 130 GHz radiation pulse-modulated at low frequencies of 5, 7, or 10 Hz, and at time-averaged incident intensity (I(AV)) up to 17 mW/cm(2) was studied at room temperature (22 degrees C), below the phase transition temperature of DPPC liposomes. At all the tested values of I(AV) a significant enhancement of the enzyme reaction rate in CA-loaded liposomes occurred when the pulse repetition rate was 7 Hz. Typically, an increase from Delta A/min = 0.0026 +/- 0.0010 (n = 11) to Delta A/min = 0.0045 +/- 0.0013 (n = 12) (P < 0.0005) resulted at I(AV) = 7.7 mW/cm(2). The effect of 130 GHz pulse-modulated at 7 Hz was also observed on cationic liposomes formed with palmitoyloleoyl phosphatidylcholine (POPC), at room temperature (22 degrees C), above the phase transition temperature of POPC liposomes.