Bożena Birkenfeld

Patient-Specific Radiation Dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in Neuroendocrine Tumors

99mTc-hydrazinonicotinamide-Tyr3-octreotide (99mTc-HYNIC-TOC) is increasingly gaining acceptance as a new radiopharmaceutical for the diagnosis of pathologic lesions overexpressing somatostatin receptors. However, little information has been published about the radiation dosimetry of this agent. The aim of this study was to assess the biodistribution and radiation dosimetry of commercially available 99mTc-HYNIC-TOC. A dose calculation procedure designed to be feasible to implement in a busy clinical environment was used. Methods: Twenty-eight patients were imaged for suspected neuroendocrine tumors using a series of whole-body planar, dynamic planar, and SPECT/CT studies, after injection with 99mTc-HYNIC-TOC. Patient-specific dosimetry was performed using the OLINDA/EXM software with time-integrated activity coefficients estimated from a hybrid planar/SPECT technique. A phantom experiment was performed to establish adaptive thresholds for determination of source region volumes and activities. Results: Pathologic uptake, diagnosed as due to neuroendocrine tumors, was observed in 12 patients. Normal organs with significant uptake included the kidneys, liver, and spleen. The mean effective dose after 99mTc-HYNIC-TOC injection was 4.6 ± 1.1 mSv. Average normal-organ doses were 0.030 ± 0.012, 0.021 ± 0.007, and 0.012 ± 0.005 mGy/MBq for the spleen, kidneys, and liver, respectively. The interpatient kidney dose ranged from 0.011 to 0.039 mGy/MBq, whereas the range of tumor doses varied from 0.003 to 0.053 mGy/MBq. The ratio of tumor to kidney dose ranged from 0.13 to 2.9. The optimal thresholds for recovery of true activity in the phantom study were significantly lower than those used for volume determination. Conclusion: The patient-specific 3-dimensional dosimetry protocol used in this study is a clinically feasible technique that has been applied to demonstrate large dose variations in tumors and normal organs between patients imaged with 99mTc-HYNIC-TOC.

Recurrent mutations of BRCA1 and BRCA2 in Poland: an update

Three founder alleles of BRCA1 (C61G, 4153delA, 5382insC) were reported in Poland in 2000, and these three mutations have comprised the standard testing panel used throughout the country. However, since 2000, other recurrent mutations of BRCA1 and BRCA2 have been reported. To establish if the inclusion of one or more of these mutations will increase the sensitivity of the standard test panel, we studied 1164 Polish women with unselected breast cancer diagnosed at age of 50 or below. All women were genotyped for 12 recurrent mutations of BRCA1 and BRCA2. We identified a mutation in 83 of 1164 patients (7.1%) including 61 women with one of the original three mutations (C61G, 4153delA, 5382insC) and 22 women with a different mutation (1.9%). Three new mutations (3819del5, 185delAG and 5370C>T) were seen in multiple families. By including these three mutations in the extended panel, the mutant frequency increased from 5.2 to 6.7%. Polish women with breast cancer diagnosed at age of 50 or below should be screened with a panel of six founder mutations of BRCA1 (C61G, 4153delA, 5382insC, 3819del5, 185delAG and 5370C>T).

Quantitative SPECT/CT reconstruction for 177Lu and 177Lu/90Y targeted radionuclide therapies

We investigated the quantitative accuracy of SPECT/CT imaging studies as would be performed before and after targeted radionuclide therapy (TRT) using phantom experiments with (i) (99m)Tc, (ii) ¹⁷⁷Lu and (iii) ⁹⁰Y/¹⁷⁷Lu. While the experiment with (99m)Tc imitated a diagnostic scan, the experiments with ¹⁷⁷Lu and ⁹⁰Y/¹⁷⁷Lu modeled post-therapy acquisitions. At the next stage, we reconstructed images from pre- and post-therapy patient studies. The data were first reconstructed using two methods with limited corrections for the physics effects. Then, to generate quantitatively accurate absolute activity distributions, we applied a hybrid (model-based and window-based) reconstruction strategy where some of the physics effects were accurately modeled while corrections for other effects were empirical and based on information obtained from the projection data. The accuracies of absolute activity recovered by the hybrid method from the six phantom experiments were very similar to each other and acceptable for potential use in TRT. When measured in identical regions of interest, the (99m)Tc ⁹⁰activity was reconstructed with errors ranging between -3.3% and 2.9%, while the ¹⁷⁷Lu activity was reconstructed from experiments with ¹⁷⁷Lu and Y/¹⁷⁷Lu with errors ranging between -1.6% and 1.6%. The reconstruction algorithms with limited corrections led to larger and case-specific errors as might have been expected. From a clinical prospective, our results showed that physics-based reconstructions improved resolution of images corresponding to both diagnostic scans with (99m)Tc and post-therapy scans with ¹⁷⁷Lu. Our analysis of patient study demonstrated that lack of corrections led to overestimation of activities in organs and tumor by 29-39% for the diagnostic scan with (99m)Tc and by 105-218% for post-therapy scan with ¹⁷⁷Lu.

The accuracy and reproducibility of SPECT target volumes and activities estimated using an iterative adaptive thresholding technique.

Objective Our aim was to design a practical and reproducible image segmentation method for calculations of total absorbed doses in organs and tumours for internally delivered radioisotopes. We have built upon our previously proposed use of two separate thresholds and employed an iterative technique for semiautomatic selection of background regions for segmenting an object of interest using thresholds that depend on the source-to-background ratio of activity concentrations. Methods The parameters of curves relating volume and activity thresholds to source-to-background ratio were established using phantoms with 20 different inserts. The accuracy of our technique was validated using a second phantom experiment, whereas the reproducibility of volume, activity and dose estimates of organs and tumours was investigated using 13 patient studies. The accuracy and reproducibility of segmentations achieved were assessed using images reconstructed with three different methods that ranged from a standard clinical reconstruction to an advanced quantitative reconstruction approach. Results In the validation phantom experiment, bottle volumes and activities measured using iterative adaptive thresholding agreed on average with the true values to within 4%, regardless of the reconstruction method used. In the patient studies, volumes and activities estimated from the single-photon emission computed tomography images reconstructed with clinical software agreed with the volumes and activities estimated using the advanced reconstruction approach to within 6%, whereas the corresponding doses agreed to within 4%. Conclusion The proposed iterative adaptive thresholding technique can accurately determine object volume and activity, which allows standard clinical reconstructions to generate absorbed dose estimates that are similar to those values obtained using more advanced reconstruction methods.

Long-term monitoring of radiation exposure of employees in the department of nuclear medicine (Szczecin, Poland) in the years 1991-2007.

Occupational radiation exposure is a hazard that should be avoided or at least minimised. This study aimed to evaluate the radiation exposure of nuclear medicine department employees monitored during the 1991-2007 period, and to investigate the relationship between the annual effective doses of the personnel and the number of radioisotope procedures performed. Overall, 2014 quarterly effective whole-body doses, categorised into six occupational groups, monitored with personal dosemeters, were analysed statistically. There was a wide variation in the average annual doses among the different occupational groups. During the 17 years covered by this study, there was no incidence of a dose exceeding the annual dose limit of 20 mSv. There was a weak correlation between the average annual dose for monitored employees and the number of nuclear medicine procedures performed. Apart from exposure, personal skill in dealing with radioactive substances, compliance with radiation protection rules is an important factor to minimise the effective dose.

Evaluation of dead-time corrections for post-radionuclide-therapy (177)Lu quantitative imaging with low-energy high-resolution collimators.

ObjectivesDead-time (DT) effects rarely cause problems in diagnostic single-photon emission computed tomography (SPECT) studies; however, in post-radionuclide-therapy imaging, DT can be substantial. Therefore, corrections may be necessary if quantitative images are used in image-based dosimetry or for evaluation of therapy outcomes. This task is particularly challenging if low-energy collimators are used. Our goal was to design a simple method to determine the dead-time correction factor (DTCF) without the need for phantom experiments and complex calculations. MethodsPlanar and SPECT/CT scans of a water phantom containing a 70 ml bottle filled with lutetium-177 (177Lu) were acquired over 60 days. Two small 177Lu markers were used in all scans. The DTCF based on the ratio of observed to true count rates measured over the entire spectrum and using photopeak primary photons only was estimated for phantom (DT present) and marker (no DT) scans. In addition, variations in counts in SPECT projections (potentially caused by varying bremsstrahlung and scatter) were investigated. ResultsFor count rates that were about two-fold higher than typically seen in post-therapy 177Lu scans, the maximum DTCF reached a level of about 17%. The DTCF values determined directly from the phantom experiments using the total energy spectrum and photopeak counts only were equal to 13 and 16%, respectively. They were closely matched by those from the proposed marker-based method, which uses only two energy windows and measures photopeak primary photons (15–17%). ConclusionA simple, marker-based method allowing for determination of the DTCF in high-activity 177Lu imaging studies has been proposed and validated using phantom experiments.

Calcium-phosphate metabolism parameters and erythrocyte Ca(2+) concentration in autosomal dominant polycystic kidney disease patients with normal renal function.

Introduction The aim of this study was to assess calcium-phosphate metabolism of autosomal dominant polycystic kidney disease (ADPKD) patients with a special consideration to the following serum parameters: calcium (Ca2+), inorganic phosphate (Pi), parathyroid hormone (PTH) and intracellular erythrocyte calcium ([Ca2+]i) concentrations. Material and methods The study included 49 adult ADPKD patients (19 males, 30 females) aged 36 ±11 years with normal renal function and no diagnosis of diabetes as well as 50 healthy controls (22 males, 28 females) matched for age and gender. Serum concentrations of sodium (Na+), potassium (K+) and magnesium (Mg2+) ions and Pi were determined with an indirect ion-selective method, while Ca2+ concentration was measured with a direct ion-selective method. The PTH was detected using a radioimmunometric method. [Ca2+]i concentration was determined with the Ca2+ sensitive fluorescent dye Fura-2 method. Results In the ADPKD group, when compared to controls, the following concentrations were significantly higher: serum Ca2+ (1.18 ±0.06 mmol/l vs. 1.15 ±0.06 mmol/l, p = 0.0085), [Ca2+]i (146.9 ±110.0 nmol/l vs. 96.5 ±52.7 nmol/l, p = 0.0075), serum Na+ (139.4 ±2.7 mmol/l vs. 138.5 ±2.1 mmol/l, p = 0.060, borderline significance), and PTH (15.5 ±6.8 pg/ml vs. 13.6 ±5.3 pg/ml, p = 0.066, borderline significance), while serum Mg2+ was significantly lower (0.81 ±0.09 mmol/l vs. 0.85 ±0.05 mmol/l, p = 0.021). In the ADPKD group we observed significant negative correlations of PTH with Ca2+ serum concentrations (Rs = –0.32, p = 0.025) and with estimated glomerular filtration rate (Rs = –0.31, p = 0.033). Conclusions The erythrocyte Ca2+ concentration is elevated in ADPKD patients with normal renal function. It may result from a dysfunction of mutated polycystins which can affect various aspects of electrolyte metabolism.

Personalized Image-Based Radiation Dosimetry for Routine Clinical Use in Peptide Receptor Radionuclide Therapy: Pretherapy Experience

Patient-specific dose calculations are not routinely performed for targeted radionuclide therapy procedures, partly because they are time consuming and challenging to perform. However, it is becoming widely recognized that a personalized dosimetry approach can help plan treatment and improve understanding of the dose-response relationship. In this chapter, we review the procedures and essential elements of an accurate internal dose calculation and propose a simplified approach that is aimed to be practical for use in a busy nuclear medicine department.

Optimization of Low-Dose CT Protocol in Pediatric Nuclear Medicine Imaging

This study was performed to find the optimal low-dose CT protocol for children being imaged on SPECT/CT scanners not equipped with automatic dose control. For SPECT/CT systems with manually adjustable x-ray tube voltage (kV) and anode current (mA), an optimized protocol makes it possible to minimize the dose to patients. Methods: Using the 4-slice low-dose CT component of a commercially available SPECT/CT scanner, we compared the signals reaching the CT detector after radiation passes through objects of different sizes. First, the exit dose rates were measured for combinations of available voltages and currents. Next, imaging parameters were selected on the basis of acceptable levels of exit dose rates, cylindric phantoms of different diameters approximating children of different sizes were scanned using these parameters, and the quality of the CT images was evaluated. Finally, weighted CT dose indexes for abdomen and head CT dose phantoms simulating, respectively, adult and pediatric patients were measured using exactly the same techniques to estimate and compare doses to these 2 groups of patients. Results: For children with torsos smaller than 150 mm, imaging can be performed using the lowest available voltage and current (120 kV and 1 mA, respectively). For children with torsos less than 250 mm, 140 kV and 1.5 mA can be used. For patients with torsos greater than 250 and less than 300 mm, 140 kV and 2 mA can be used. Regarding the signal-to-noise ratio, all these parameters give an excellent signal and fully acceptable noise levels. Conclusion: For the SPECT/CT system studied, even the lowest available voltage and current used for scanning pediatric patients did not cause signal-to-noise degradation, and the use of these settings substantially lowered the dose to the patients.

Characteristics of brems Strahlung emissions from radionuclide therapy isotopes

Targeted radionuclide therapy uses radioisotopes that emit beta particles. Some of these isotopes also emit gamma lines that can be used to image the radiotracer distribution. In all these cases, the gammas detected by the SPECT camera are accompanied by a bremsstrahlung background. Here, we have performed several simulations and experiments in order to investigate the energy distribution and yields of the bremsstrahlung emissions for several radioisotopes used in radionuclide therapy. Different types of collimators were simulated, and the shape of the detected spectrum was compared with experiment, The simulations performed in this study strongly suggest that bremsstrahlung for non-pure beta emitters contribute little to the detected spectra.