Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice

Background To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. Methods Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. Results A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. Conclusion This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

351 Prevalence and prognostic significance of RV uptake (biventricular uptake) at planar scintigraphy in patients with ATTR cardiac amyloidosis

Aims The validation of cardiac scintigraphy with bone tracers for nonbiopsy confirmation of transthyretin cardiac amyloidosis (ATTR-CA) has revolutionized the diagnosis of this condition. While most studies focused on left ventricle (LV) uptake, the significance of bone tracers uptake in the right ventricle (RV) leading to biventricular (BiV) uptake has not been investigated so far. BiV uptake at planar scintigraphy might reflect a more advanced ATTR-CA. To estimate the prevalence of BiV uptake and its potential prognostic role in ATTR-CA. Methods and results Multicentre, retrospective, observational study performed among four Italian referral centres for CA. Data of ATTR-CA patients who underwent bone tracers scintigraphy with acquisition of planar and SPECT imaging between November 2014 and June 2020 at participating centres were centrally revised. ATTR-CA was diagnosed according to the Gilmore’s algorithm. LV uptake was assessed by Perugini visual scale. RV uptake was defined as: 0 = absent, 1 ≤ bone uptake, 2 = equal to bone uptake, and 3 ≥ bone uptake. Images were independently assessed by six experienced operators, blinded to all patients’ data. Cardiological data included clinical examination, ECG, echocardiography and blood tests. The primary outcome was a composite of cardiac death and hospitalization for heart failure. Of the 124 patients with ATTR-CA included in this analysis, 93 (75%) had BiV uptake at planar scintigraphy and all had RV free wall uptake confirmed at SPECT imaging. The prevalence of planar BiV uptake increased along with the LV Perugini grade: 14% in Perugini grade 1, 70% in Perugini grade 2, and 92% in Perugini grade 3. Compared to those with planar LV uptake, patients with planar BiV uptake were older (81 vs. 77 years, P = 0.006), more frequently in NYHA ≥3 (32% vs. 10%, P = 0.018), had increased NT-proBNP values (4293 vs. 2492 pg/ml, P = 0.046), LV wall thickness (18 vs. 17 mm, P = 0.007). They had higher rates of LV ejection fraction <50% (42% vs. 10%, P = 0.001) and lower TAPSE (16 vs. 20 mm, P = 0.048). At 18 months, patients with BiV uptake experienced the primary endpoint more frequently than those with LV uptake (P = 0.021, Figure), with the highest risk observed in patients with grade 2–3 RV uptake (P = 0.010). The LV Perugini grade did not affect prognosis (P = 0.20). At multivariate analysis, NYHA ≥3, eGFR <60 ml/min and BiV uptake had independent prognostic value (HR 8.0, P = 0.007; HR 2.1, P = 0.025; HR 1.7, P = 0.007; respectively). Conclusions The presence of BiV uptake at planar scintigraphy identified ATTR-CA patients at worse cardiovascular outcome, potentially serving as novel marker for prognostic stratification in this population.

PLANAR SCINTIGRAPHY IMAGE DE-NOISING USING COIFLET WAVELET

The planar scintigraphic image usually has poor resolution and contains noise. This noise can be removed using the coiflet wavelet method so that the image quality gets better. This coiflet wavelet method is a noise reduction method based on frequency analysis. The planar scintigraphy image is the reconstructed image of the gamma radiation count data (phantom with the Cs-137 source in it). The original image is 15×15 pixel. Before the de-noising process, the image went through an interpolation process, which is to increase the pixel size of the image. The original image enlarged to 70×70, 480×480, and 1200×1200 pixel. After de-noising with coiflet wavelet, the image quality is measured based on MSE and PSNR parameters. The resulting images are quite good, with MSE values are close to zero and PSNR values of more than 60 dB. The smaller the MSE and the bigger the PSNR, is getting the better the image quality. In this study, the results show that the 1200×1200 pixel image has the best quality. It means that the image enlargement process has a good effect on the de-noising process, especially if the original image has a low resolution.

EVALUATION OF EXTENT OF BREAST CANCER IN A PATIENT WITH HER2/NEU OVEREXPRESSION USING A RADIOPHARMACEUTICAL BASED ON TECHNETIUM-99M-LABELED TARGET MOLECULES (CASE REPORT)

Introduction. Overexpression of Her2/neu is detected in 15–20 % of patients with breast cancer and associated with an aggressive form of disease and low overall and disease-free survival rates. Currently, immunohistochemical studies (IHC) and methods of in situ hybridization are used to assess Her2/neu status. One of significant drawbacks of this detection is the impossibility of simultaneous assessment of the receptor status of the primary tumor and metastatic sites. The increasing popularity of radionuclide methods using recombinant proteins as a targeting module have already demonstrated their effectiveness in solving this question at the initial stages of clinical research.The purpose of this study is to demonstrate a clinical case of assessing the extent of breast cancer in a patient with overexpression of Her2/neu using a radiopharmaceutical based on targeted protein molecules labeled with technetium-99m.Description of the clinical case. A patient diagnosed with stage IIIA right breast cancer (T2N2M0), multicentric growth and metastases in right axillary and subclavian lymph nodes at the diagnostic stage was injected intravenously with 99mTc-ADAPT6 radiopharmaceutical. The drug was prepared in the Department of Nuclear Medicine of Research Cancer Institute (Tomsk) immediately before its administration. Planar scintigraphy and singlephoton emission tomography of the chest organs were performed 2 hours after injection of 99mTc-ADAPT6 radiopharmaceutical. In addition to the previously described tumors, 3 foci of hyperfixation of the tracer in the projection of the 5th rib on the right along the middle-clavicular line, as well as in the projection of the 8 and 9 thoracic vertebrae (Th VIII, IX) were found. Computed tomography of the chest organs and bone scintigraphy with 99mTc-pyrophosphate showed no metastases in the 5th rib on the right and Th VIII, IX. Magnetic resonance imaging of the thoracic spine revealed 2 metastatic foci in Th VIII, IX. Planar scintigraphy with 99mTc-pyrophosphate and CT performed 6 months after injection of 99mTc-ADAPT6 revealed previously described foci in the projection of the thoracic spine (Th VIII, IX) and 5 ribs on the right along the mid-clavicular line. Conclusion. The results demonstrated during the study suggest that 99mTc-ADAPT6 is a promising tracer for molecular imaging of tumor foci with overexpression of the Her2/neu receptor in breast cancer patients.

Рreoperative diagnosis of parathyroid gland pathology by methods of radiological diagnostics

Introduction. Recently, surgeons have been using minimally invasive methods to treat parathyroid gland pathology. More selective surgical approaches are based on the accuracy of preoperative diagnostic methods. Various radiological diagnostic techniques are used to visualize parathyroid gland pathology. New modalities are entering clinical practice along with long-known techniques. The attending physician should be guided by the most clinically effective and economically reasonable algorithm when choosing diagnostic algorithm. The aim of the study was to find the optimal diagnostic protocol for preoperative diagnosis of parathyroid gland pathology on the basis of available data. Conclusion. Preoperative imaging of parathyroid glands continues to evolve with changes of old techniques and appearance of new ones, though none of modalities has a clear advantage. The choice of imaging algorithm is largely based on the availability of techniques and the experience of particular diagnostic centers. Ultrasound and planar scintigraphy are well established and most widely used. The combination of these techniques remains the first line of diagnosis in preoperative imaging. However, there is no consensus on the choice between planar scintigraphy tech niques: the washout method or the subtraction method. Replacing planar scintigraphy with SPECT/CT improves the detectability of pathological masses and clarifies their topographic location. Computed tomography and MRI techniques are used as a second-line technique and have an advantage in small adenoma sizes, multiple lesions, ectopias, reoperations, and in case of ambiguous ultrasound and scintigraphy data. The significance of PET/CT in the diagnosis of thyroid pathology has not yet been defined, the data are still scarce and published studies are very heterogeneous, but due to the excellent diagnostic characteristics the method seems very promising, in particular in patients with persistent disease.

Imaging cardiac innervation

Cardiac autonomic nervous system contributes to maintain haemodynamic and electrophysiological stability to changing demands. Cardiac innervation imaging can be performed by means of planar scintigraphy/SPECT or PET using different radiotracers developed for the assessment of pre- and postsynaptic receptors of the cardiac autonomic nervous system, with sufficient sensitivity to assess a process that takes place at picomolar concentrations. Clinically, cardiac innervation imaging is mainly performed targeting postganglionic presynaptic sympathetic neurons by means of myocardial 123I-metaiodobenzylguanidine (123I-mIBG) planar scintigraphy and SPECT, which has shown to be of value in the assessment of patients with different cardiac disorders, especially in those with heart failure (HF), having an independent prognostic value. This clinically oriented chapter updates the subject with inclusion of new data reinforcing the use of sympathetic cardiac innervation imaging for improving patient management.