Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine.

Dementia (the most common cause of Alzheimer's disease) is defined as a chronic or progressive syndrome with disturbance of multiple cortical functions, the most important of them including memory, learning capacity, comprehension, orientation, calculation, language, and judgement. These cognitive impairments affect the quality of life, behavior, and social relations. Techniques of nuclear medicine provide feasible ways to record the intracellular alterations of disease and deficiencies. In these non-invasive manners, the hippocampal-neocortical disconnection may partly explain the hypo-metabolism incident found in Alzheimer's disease. Based on this fact, the study of all these mechanisms of action is conceivable and achievable by radiopharmaceuticals. This review is aimed at the presentation of radiopharmaceuticals that are developed for the detection of Alzheimer's disease in preclinical and clinical trials.

Optimal Indications of Radioimmunotherapy in Nuclear Medicine: A Mini-Review.

Immunotherapy has emerged as a very considerable and potent therapeutic method in which immune inhibitors have gained a lot of attention in the curative field of various cancers. Under certain circumstances, when radiotherapy is accompanied by immunotherapy, the efficacy of the therapeutic procedure increases. Irradiated tumor cells follow a pathway called immunogenic cell death, which targets tumor associated antigens. The application of radiolabeled antibodies under the concept of "radioimmunotherapy" (RIT) makes the synergistic targeted therapeutic effect possible. Since antibodies themselves are cytotoxic, they can kill the cells that not only bind but are within the path length of their radiation emissions. RIT can be categorized as a substantial progress in nuclear medicine. The main concept of RIT includes targeting specified tumor-expressing antibodies. The mentioned purpose is achievable by formulation of radiolabeled antibodies, which could be injected intravenously or directly into the tumor, as well as compartmentally into a body cavity such as the peritoneum, pleura, or intrathecal space. RIT has demonstrated very optimistic therapeutic outcomes in radioresistant solid tumors. Wide ranges of efforts are accomplished in order to improve clinical trial accomplishments. In this review, we intend to summarize the performed studies on RIT and their importance in medicine.

FAPI PET/CT provides higher uptake and better target to back ground in recurrent and metastatic tumors of patients with Iodine refractory papillary thyroid cancer compared with FDG PET CT.

PURPOSE: The role of fibroblast activation protein inhibitor (FAPI) PET CT scan is not well documented in papillary thyroid cancer (PTC) patients. Patients with radioiodine refractory PTC and high thyroglobulin levels need PET/CT scan which is generally done by 18F FDG. In the current study, the diagnostic performance of 68Ga FAPI and FDG PET/CT scans were compared head to head in patients with radioiodine refractory PTC. METHOD: Fourteen patients with negative whole body Iodine scans and high thyroglobulin levels underwent whole body PET scans with, respectively, 120-310 and 145-370 MBq 68Ga FAPI-46 and 18F FDG. SUVmax of the back ground in the blood pool and liver and the hottest, largest and average neck, mediastinum, lung and bone lesions were calculated and compared. RESULT: Ten patients had at least one active (SUVmax>blood pool) lesion similarly in two scans. The liver and blood pool SUVmax values were 1.25(0.2) and 1.7(0.2) in FAPI and 2.65(0.2) and 2.0(0.2) in FDG PET images, respectively. The difference was significant (p=0.001). Standard SUV of the hottest lesion to liver was above 3 in all FAPI scans but in half of FDG scans. Target lesion number and intensity were similar between two PET studies but in a patient out of 5 pulmonary metastatic patients, pulmonary nodules were negative (SUVmax=0.9) in FDG while positive (SUVmax= 3.8) in FAPI images (i.e. 20% patient upstaged). CONCLUSION: FAPI accumulates in the recurrent and metastatic lesions of patients with Iodine refractory PTC at least as well as FDG with particular privileges as lower injected activity and lower back ground.

Optimization of the Acquisition Time and Injected Dose of 18 F-Fluorodeoxyglucose Based on Patient Specifications for High-Sensitive Positron Emission Tomography/Computed Tomography Scanner.

Background This study was aimed to optimize the fluorodeoxyglucose (FDG)-administered dose and scan time based on patient specifications using a highly sensitive five-ring bismuth germanium oxide (BGO)-based positron emission tomography/computed tomography (PET/CT) scanner (Discovery IQ). Methods We retrospectively analyzed 101 whole-body 18 F-FDG PET/CT images. Patient data were reconstructed using ordered subset expectation maximization with resolution recovery algorithms (OSEM + SharpIR). Signal-to-noise ratio (SNR) was calculated for each patient, standardized to SNR norm , and plotted against three body index parameters (weight, body mass index, and lean body mass). Two professional physicians blindly examined image quality at different patient time per bed positions to determine the minimum acceptable quality. To select images of acceptable quality, the noise index parameter was also measured. A new dose-time product (DTP) was established for each patient, and a predicted injected dose was assumed. Results We found an almost linear association between patient weight and normalized SNR, and patient weight had the highest R 2 in the fitting. The redesigned DTP can reduce results by approximately 74 and 38% compared with ordinary DTP for 80- and 160-s scan durations. The new dose regimen formula was found to be DTP = c/t × m 1.24 , where m is the patient weight, t is the scan time per bed position, and c is 1.8 and 4.3 for acceptable and higher confidence states, respectively, in Discovery IQ PET/CT. Conclusion Patient weight is the best clinical parameter for the implementation of 18 F-FDG PET/CT image quality assessment. A new dose-time regimen based on body weight was proposed for use in highly sensitive five-ring BGO PET-CT scanners to significantly reduce the injection dose and scan times while maintaining sufficient image quality for diagnosis.

Phantom and clinical evaluation of Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm in 68Ga-PSMA PET-CT studies.

In this study, we aimed to examine the effect of varying ß-values in the block sequential regularized expectation maximization (BSREM) algorithm under differing lesion sizes to determine an optimal penalty factor for clinical application. The National Electrical Manufacturers Association phantom and 15 prostate cancer patients were injected with 68Ga-PSMA and scanned using a GE Discovery IQ PET/CT scanner. Images were reconstructed using ordered subset expectation maximization (OSEM) and BSREM with different ß-values. Then, the background variability (BV), contrast recovery, signal-to-noise ratio, and lung residual error were measured from the phantom data, and the signal-to-background ratio (SBR) and contrast from the clinical data. The increment of BV using a ß-value of 100 was 120.0%, and the decrement of BV using a ß-value of 1000 was 40.5% compared to OSEM. As ß decreased from 1000 to 100, the [Formula: see text] increased by 59.0% for a sphere with a diameter of 10 mm and 26.4% for a sphere with a diameter of 37 mm. Conversely, [Formula: see text] increased by 140.5% and 29.0% in the smallest and largest spheres, respectively. Furthermore, the Δ[Formula: see text] and Δ[Formula: see text] were - 41.1% and - 36.7%, respectively. In the clinical study, OSEM exhibited the lowest SBR and contrast. When the ß-value was reduced from 500 to 100, the SBR and contrast increased by 69.7% and 71.8% in small and 35.6% and 33.0%, respectively, in large lesions. Moreover, the optimal ß-value decreased as lesion size decreased. In conclusion, a ß-value of 400 is optimal for small lesion reconstruction, while ß-values of 600 and 500 are optimal for large lesions in phantom and clinical studies, respectively.

Impact of Region-of-Interest Delineation on Stability and Reproducibility of Liver SNR Measurements in 68 Ga-PSMA PET/CT.

Objective This study aims to assess the impact of various regions of interest (ROIs) and volumes of interest (VOIs) delineations on the reproducibility of liver signal-to-noise-ratio (SNRliver) measurements, as well as to find the most reproducible way to estimate it in gallium-68 positron emission tomography ( 68 Ga-PET) imaging. We also investigated the SNRliver-weight relationship for these ROIs and VOIs delineations. Methods A cohort of 40 patients (40 males; mean weight: 76.5 kg [58-115 kg]) with prostate cancer were included. 68 Ga-PET/CT imaging (mean injected activity: 91.4 MBq [51.2 MBq to 134.1 MBq] was performed on a 5-ring bismuth germanium oxide-based Discovery IQ PET/CT using ordered subset expectation maximization image reconstruction algorithm. Afterward, circular ROIs and spherical VOIs with two different diameters of 30 and 40 mm were drawn on the right lobe of the livers. The performance of the various defined regions was evaluated by the average standardized uptake value (SUV mean ), standard deviation (SD) of the SUV (SUV SD ), SNR liver , and SD of the SNR liver metrics. Results There were no significant differences in SUV mean among the various ROIs and VOIs ( p > 0.05). On the other hand, the lower SUV SD was obtained by spherical VOI with diameter of 30 mm. The largest SNR liver was obtained by ROI (30 mm). The SD of SNR liver with ROI (30 mm) was also the largest, while the lowest SD of SNR liver was observed for VOI (40 mm). There is a higher correlation coefficient between the patient-dependent parameter of weight and the image quality parameter of SNRliver for both VOI (30 mm) and VOI (40 mm) compared to the ROIs. Conclusion Our results indicate that SNR liver measurements are affected by the size and shape of the respective ROIs and VOIs. The spherical VOI with a 40 mm diameter leads to more stable and reproducible SNR measurement in the liver.

Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [64Cu]Cu-DOTA-TOC.

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [111In]In-pentetreotide, [99mTc]Tc-HYNIC-TOC/TATE, [68Ga]Ga-DOTA-TATE, and [64Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (177Lu) and Actinium-225 (225Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [64Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.

Evaluation of Annual Staff Doses and Radiation Shielding Efficiencies of Thyroid Shield and Lead Apron during Preparation and Administration of 131I, 81Kr, and 99mTc-Labeled Radiopharmaceuticals.

Nuclear medicine technicians would receive unavoidable exposures during the preparation and administration of radiopharmaceuticals. Based on the staff dose monitoring, the dose reduction efficiencies of the radiation protection shields and the need to implement additional strategies to reduce the staff doses could be evaluated. In this study, medical staff doses during the preparation and administration of Tc-99 m, I-131, and Kr-81 radiopharmaceuticals were evaluated. The dose reduction efficiencies of the lead apron and thyroid shield were also investigated. GR-207 thermoluminescent dosimeter (TLD) chips were used for quantifying the medical staff doses. The occupational dose magnitudes were determined in five organs at risk including eye lens, thyroid, fingers, chest, and gonads. TLDs were located under and over the protective shields for evaluating the dose reduction efficiencies of the lead apron and thyroid shield. The occupational doses were normalized to the activities used in the working shifts. During preparation and injection of Tc-99 m radiopharmaceutical, the average annual doses were higher in the chest (4.49 mGy) and eye lenses (4 mGy). For I-131 radiopharmaceutical, the average annual doses of the point-finger (15.8 mGy) and eye lenses (1.23 mGy) were significantly higher than other organs. During the preparation and administration of Kr-81, the average annual doses of the point-finger (0.65 mGy) and chest (0.44 mGy) were higher. The significant dose reductions were achieved using the lead apron and thyroid shield. The radiation protection shields and minimum contact with the radioactive sources, including patients, are recommended to reduce the staff doses.

Myocardial perfusion imaging and appropriateness of the test for preoperative cardiac risk evaluation in an Iranian population: clinical role of Duke Activity Status Index.

OBJECTIVE: For preoperative radionuclide myocardial perfusion imaging, metabolic equivalent is one of the key factors to evaluate the appropriateness. Duke Activity Status Index is a practical method to calculate metabolic equivalents. We intended to validate Duke Activity Status Index in our population for the assessment of preoperative myocardial perfusion imaging appropriateness. METHODS: A total of 542 patients referred for myocardial perfusion imaging were recruited. A questionary compiled from Duke Activity Status Index was filled out based on which metabolic equivalents were calculated. Demographic data and history of cardiac risk factors were also collected. Myocardial perfusion imaging was performed using a 2-day stress-rest protocol either by exercise tolerance test or by pharmacologic stress through injection of Tc-MIBI and imaging by a dual-head gamma camera. RESULTS: Out of 542 patients, 369 (68.1%) were evaluated for preoperative risk assessment. Metabolic equivalents (oxygen consumption/min/kg) were calculated at 9.3 ± 5.1, 10.8 ± 4.8, and 8.7 ± 5.1 in total, preoperative patients and patients evaluated for ischemia due to nonsurgical purposes, respectively (p = 0.001). The myocardial perfusion imaging was rarely appropriate in 291 (79.5%), maybe appropriate in 67 (18.3%), and appropriate in 8 (2.2%) patients. The prevalence of abnormal myocardial perfusion imaging was 22.5%, 28.4%, and 12.5% in "rarely appropriate," "maybe appropriate," and "appropriate" scenarios, respectively. Metabolic equivalents were similar between patients with normal and abnormal myocardial perfusion imaging (8.7 ± 5.0 vs. 8.5 ± 5.4). CONCLUSION: Either Duke Activity Status Index is not a proper tool for calculation of metabolic equivalents or the appropriate use criteria is not operational in the population of Iranian preoperative patients in which cultural factors may contribute.

A preliminary study to propose a diagnostic algorithm for PET/CT-detected incidental breast lesions: application of BI-RADS lexicon for US in combination with SUVmax.

OBJECTIVES: To develop a diagnostic algorithm for positron emission tomography (PET)-detected incidental breast lesions using both breast imaging reporting and data system (BI-RADS) and maximum standardized uptake value (SUVmax) criteria. METHODS: Fifty-six PET-detected incidental breast lesions from 51 patients, which were subsequently investigated by breast ultrasound within 1 month of the PET study, constituted the study cohort and they were finally verified by tissue diagnosis or a 2-year follow-up. Based on the maximum specificity with sensitivity > 60.0% and maximum sensitivity with specificity > 60.0%, two SUVmax cutoff values were calculated at 2 and 3.7. BI-RADS ≥ 4 was considered as highly suspicious for malignancy. The diagnostic accuracies were estimated for SUVmax levels above or below the cutoff points combined with the BI-RADS suspicion level. RESULTS: Overall, 46 benign and 10 malignant lesions were studied. The diagnostic characteristics of SUVmax ≥ 2, SUVmax ≥ 3.7, and BI-RADS ≥ 4 were 80.0%, 60.0%, and 80.0% for sensitivity, 73.9%, 95.7%, and 92.7% for specificity, and 75.0%, 89.3%, and 90.2% for accuracy, respectively. When the SUVmax threshold was set at 2, combined with BI-RADS suspicion level, the sensitivity, specificity, and accuracy were 100.0%, 69.6%, and 75.0%, respectively. The results for SUVmax threshold set at 3.7 combined with BI-RADS were 90.0%, 91.3%, and 91.1% for the sensitivity, specificity, and accuracy, respectively. A diagnostic algorithm was accordingly generated. CONCLUSION: The need for biopsy should be justified in low BI-RADS lesions presenting with high SUVmax at 3.7 or higher. The biopsy of patients with high B-IRADS and low SUVmax could be preserved. KEY POINTS: • A diagnostic algorithm was developed for PET-detected incidental breast lesions using both BI-RADS and SUVmax criteria. • Diagnostic performance was calculated separately and conjunctively for SUVmax ≥ 2, SUVmax ≥ 3.7, and BI-RADS ≥ 4. • The need for biopsy can be justified in BI-RADS < 4 lesions with SUVmax ≥ 3.7. Lesions with BI-RADS < 4 and indeterminate SUVmax (2 < SUVmax < 3.7) benefit from a short-interval follow-up. BI-RADS < 4 lesions with SUVmax < 2 may confidently be scheduled for routine screening.

CT-measured pulmonary artery diameter as an independent predictor of pulmonary hypertension in cystic fibrosis.

PURPOSE: The role of computed tomography (CT) scan, as a promising prognostic imaging modality in cystic fibrosis (CF), has been widely investigated, focusing on parenchymal abnormalities. The aim of the present study was to evaluate the diagnostic performance of thoracic vascular parameters on CT to detect pulmonary hypertension (PH). MATERIAL AND METHODS: CF patients who contemporaneously underwent CT and echocardiography were retrospectively enrolled. Baseline characteristics in addition to pulmonary artery diameter (PAD) and pulmonary to aortic (PA/A) ratio were compared between cohorts with and without PH, based on the results of echocardiography separately in paediatric patients (< 18) and adults (≥ 18). RESULTS: Of a total 119 CF patients, 39 (32.8%) had PH (paediatric: 23/78, 29.5%, adult: 16/41, 39%). In paediatric CF patients, mean age, HCo3, PCo2, and pulmonary artery diameter (PAD) were significantly higher in the PH group compared to the non-PH group. Mean pulmo however, only PAD remained as the independent predictor of PH based on multivariate analysis (overall: 22.86 mm [±3.86] vs. 18.43 mm [±4.72], p = 0.005, paediatric patients: 22.63 mm [±4.4] vs. 17.10 mm [±4.64], p = 0.03). Using a cut off of 19.25 mm, the diagnostic performance of PAD to detect PH was found to be as follows: sensitivity = 82%, specificity = 70%, and accuracy = 73.1%. No significant difference was demonstrated in PAD between PH and non-PH groups in adults with CF (23.19 [±3.60] vs. 21.34 [±3.49], p = 0.7). CONCLUSIONS: In CF patients, PAD revealed an age-dependent performance to detect PH. PAD can be applied to predict pulmonary hypertension in paediatric CF patients and may be recommended to be routinely measured on follow-up chest CT scan in childhood CF.

Reverse perfusion pattern in myocardial perfusion imaging using technetium-99m-sestamibi in patients with intermediate risk for coronary artery disease in relation to the time of acquisition and intensity of visceral uptake as artifactual causes.

OBJECTIVE: With respect to the equivocal value of the reverse perfusion pattern (RPP) in technetium-99m (Tc)-sestamibi myocardial perfusion imaging, a study was carried out to evaluate this pattern in association with the presence or absence of coronary artery disease (CAD) and other underlying factors, mainly the time of acquisition and the presence of intense visceral uptake. PATIENTS AND METHODS: We prospectively studied 102 patients with a moderate risk of CAD (41 men and 61 women, mean age: 56.5±9.2 years) without a previous history of documented CAD, myocardial infarction, or revascularization. Myocardial perfusion imaging was performed using a 2-day dual-phase protocol with the stress and rest images, each obtained 15, 120, and 180 min after an injection of 666-814 MBq Tc-MIBI. According to the time of image acquisition, the following five protocols were defined, A: 15/15 min, B: 15/180 min, C: 180/180 min, D: 180/15 min, and E: 120/120 min for stress/rest images, respectively. RESULTS: The odds of RPP were higher in the cases with more intense infradiaphragmatic visceral uptake on rest-phase images of the protocols A and D (odds ratios=1.2-7.8 and 1.2-7.5, respectively). Our results showed that RPP is related to incorrect normalization. Also, diabetes, sex, and CAD did not correlate with RPP. CONCLUSION: This study found no relationship between RPP and CAD, diabetes mellitus, and sex; however, an association was found between RPP and incorrect normalization because of the variation of visceral uptake intensity in relation to the time of acquisition at stress and rest phases favoring the artifactual base of this pattern.

Comparative evaluation of the diagnostic accuracy of (99m)Tc-sestamibi gated SPECT using five different sets of image acquisitions at stress and rest phases for the diagnosis of coronary artery disease.

On the basis of some new evidences in favor of delayed (99m)Tc methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) redistribution, doubts about the appropriate time of acquisition following radiotracer injection may be raised. The goal of this study was to find the best acquisition time at stress and rest phases to achieve the highest sensitivity and normalcy rate for (99m)Tc-MIBI SPECT. Ninety four patients with moderate pretest probability of coronary artery disease (CAD) according to "Framingham Risk Score" enrolled in the study. Myocardial perfusion imaging (MPI) with SPECT was performed on the basis of two-day protocol with stress- and rest-phase images obtained at 15, 60, 120 and 180 minutes after injection of 666-814 MBq (99m)Tc-MIBI. According to the time of image acquisition at stress/rest phases, five protocols were defined: A, 15/180 min, B, 15/15 min, C, 180/180 min, D, 180/15 min and E, 120/120 min for stress and rest images, respectively. The sensitivity of MPI for the diagnosis of angiographically proven CAD were 77.3%, 50%, 63.6%, 45.5%, 68.2% and normalcy rate were 72.1%, 72.1%, 75.5%, 70.6%, 92.6% in protocol A, B, C, D and E, respectively. A significant association between SSS and Gensini score was detected only with protocol A (p=0.038). The most sensitive and specific two-day protocols for MPI with (99m)Tc-MIBI were protocol A and E, respectively. In addition, the best relationship between scintigraphic score of ischemia and angiographic score of CAD was achieved using protocol A (i.e. early acquisition at stress phase and late acquisition at rest phase).