Positron Emission Tomography Examination Research Articles

Nuclear medicine practice in Japan: a report of the ninth nationwide survey in 2022.

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11million which means increase in 2.7% in 5years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5years. 18F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11C-methionine, 13N-NH3 and 11C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131I-MIBG and for neuroendocrine tumor with 177Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131I-radioiodine and 223Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131I-radioiodine targeted therapy showed a decrease in 5years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110MBq of 131I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131I-MIBG and 177Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role ofnuclear medicine.

Higher Dietary Inflammatory Index scores are associated with higher beta‐amyloid deposition in the Framingham Heart Study

AbstractBackgroundHigh Inflammatory content of diet enhances systemic chronic inflammation, a pathway which plays an important role in the development and progression of dementia. We investigated the cross‐sectional relationships between long‐term Dietary Inflammatory Index (DII) scores and beta‐amyloid(Aβ) and tau Positron Emission Tomography(PET) among participants of the community‐based Framingham Heart Study(FHS).Method343 adults (mean age 58 years [standard deviation (SD)], 10; 51% women]) completed a validated 126‐item Food Frequency Questionnaire (FFQ). We created a DII score (based on the published method by Shivappa et al. 2014) based on previous studies linking individual dietary factors to six inflammatory markers (i.e. C‐reactive protein, interleukin (IL)‐1β, IL‐4, IL‐6, IL‐10 and tumor necrosis factor‐alpha), consisting of 34 components. A cumulative DII score was calculated by averaging across two FFQs (administered at FHS Generation 2(GEN2) examination cycles 8(2005‐2008) and 9(2011‐2014), and at Generation 3(GEN3) examination cycles 2 (2008‐2011) and 3 (2016‐2019). Cumulative DII scores were examined as a continuous variable and using median‐split(‐1.11). Aβ and tau PET examinations were conducted(2016‐2021) using synthesized 11C‐Pittsburgh compound B(PiB) and/or F‐18‐flortaucipir(FTP) tracers. Examination cycles 9(GEN2) and 3(GEN3) were considered as study baseline. We used linear regression to relate the cumulative DII score to Aβ (Fronto‐lateral‐retrosplenial uptake(FLR) and precuneus) and tau (entorhinal, inferior temporal, rhinal, cortical composite and global composite) PET regions.ResultHigher cumulative DII scores, as compared to DII scores below the median, were associated with higher amyloid precuneus region (β±SE, 0.023±0.011,p = 0.042) after adjustment for age, age‐squared, sex, camera and time between DII exam and PET scan exam. No other relationships were observed between DII and Aβ and tau PET. Interaction analyses showed interactions between DII (median‐split) and age (median‐split 58y) when testing association between median‐split DII and Aβ regions and tau global composite region. Stratified analyses showed relationships between higher DII vs. below median DII and higher amyloid FLR and precuneus region (0.055 ± 0.055,p = 0.037; 0.050±0.022,p = 0.022,respectively) among individuals aged 58y>, but not among individuals <58y (‐0.004±0.006,p = 0.947;0.000±0.000,p = 0.999,respectively). There were no significant interactions by sex and apolipoproteinE4 status in the association between DII and Aβ and tau PET.ConclusionHigher DII scores were associated with increased Aβ deposition.

Parametric and non-parametric Poisson regression for modelling of the arterial input function in positron emission tomography

Full quantification of Positron Emission Tomography (PET) requires an arterial input function (AIF) for measurement of certain targets, or using particular radiotracers, or for the quantification of specific outcome measures. The AIF represents the measurement of radiotracer concentrations in the arterial blood plasma over the course of the PET examination. Measurement of the AIF is prone to error as it is a composite measure created from the combination of multiple measurements of different samples with different equipment, each of which can be sources of measurement error. Moreover, its measurement requires a high degree of temporal granularity for early time points, which necessitates a compromise between quality and quantity of recorded samples. For these reasons, it is often desirable to fit models to this data in order to improve its quality before using it for quantification of radiotracer binding in the tissue. The raw observations of radioactivity in arterial blood and plasma samples are derived from radioactive decay, which is measured as a number of recorded counts. Count data have several specific properties, including the fact that they cannot be negative as well as a particular mean-variance relationship. Poisson regression is the most principled modelling strategy for working with count data, as it both incorporates and exploits these properties. However, no previous studies to our knowledge have taken this approach, despite the advantages of greater efficiency and accuracy which result from using the appropriate distributional assumptions. Here, we implement a Poisson regression modelling approach for the AIF as proof-of-concept of its application. We applied both parametric and non-parametric models for the input function curve. We show that a negative binomial distribution is a more appropriate error distribution for handling overdispersion. Furthermore, we extend this approach to a hierarchical non-parametric model which is shown to be highly resilient to missing data. We thus demonstrate that Poisson regression is both feasible and effective when applied to AIF data, and propose that this is a promising strategy for modelling blood count data for PET in future.

Multiparameter diagnostic model based on 18F-FDG positron emission tomography and serological examination for differentiating focal autoimmune pancreatitis from pancreatic ductal adenocarcinoma.

18F-fluorodeoxyglucose positron emission tomography-computerized tomography (18F-FDG PET-CT) has demonstrated high sensitivity in the diagnosis of autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC), while also exhibiting the ability to distinguish AIP from PDAC lesions. The objective of this investigation was to assess the efficacy of multiparametric 18F-FDG PET with serological examination for distinguishing focal AIP (f-AIP) from PDAC. A total of 127 patients (43 with f-AIP and 84 with PDAC) who received 18F-FDG PET-CT before treatment were retrospectively included in the cohort study conducted at two centers, Beijing Friendship Hospital and Chinese PLA General Hospital, from January 2015 to December 2021. The baseline characteristics and clinical data were collected. The metabolism parameters of 18F-FDG PET, including maximum standardized uptake value (SUVmax), tumor-to-normal liver SUV ratio (SUVR), mean SUV (SUVmean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were evaluated. The area under the receiver operating characteristic (ROC) curve was used to evaluate the differential diagnostic efficacy. The diagnostic efficacy improvement was assessed through the integrated discriminatory improvement (IDI), net reclassification improvement (NRI), and DeLong test. Serum immunoglobulin G4 (IgG4) >280 mg/dL, carbohydrate antigen 19-9 (CA19-9) <85 U/mL, and metabolic parameters differed significantly between patients with f-AID and PDAC. The ROC curve analysis of MTV showed the highest differentiating diagnostic value [sensitivity =0.814, 95% confidence interval (CI): 0.661-0.911; specificity =0.893, 95% CI: 0.802-0.947; area under the curve (AUC) =0.890, 95% CI: 0.820-0.957]. The combined diagnostics model of serum IgG4 >280 mg/dL, CA19-9 <85 U/mL, and MTV resulted in the highest AUC of 0.991 (95% CI: 0.978-1.000; sensitivity =0.953, 95% CI: 0.829-0.992; specificity =0.964, 95% CI: 0.892-0.991). The multiparameter diagnostic model based on 18F-FDG PET and serological examination has excellent clinical value in the differential diagnosis of f-AID and PDAC.

The clinical impact of amino acid positron emission tomography measurements in the treatment of primary malignant brain tumors

Despite the large-scale diagnostic and therapeutic progress of recent years, the heterogeneity and therapeutic management of adult primary malignant brain tumors pose a significant challenge to the attending physician. Based on the research and experience accumulated over the past two decades, the range of patients who can benefit the most from complex oncology treatment has been outlined, and it has been confirmed that a reliable complex diagnostic background is essential for adequate therapeutic management. However, after some necessary therapeutic steps, the "gold standard" magnetic resonance imaging (MRI) is not always able to accurately assess and diagnose post-therapeutic conditions. Thanks to the collaboration of the nuclear medicine and neuro-oncology professions, more and more types of radiotracer compounds are now available in more and more centers, including amino acid ligands and thus, positron emission tomography (PET) examinations with the radiopharmaceutical O-(2-[18F]fluoroethyl)-L-tyrosine. The metabolic state, as a kind of fourth dimension of imaging, is an essential part of adequate modern diagnostics. Combining advanced MRI techniques and PET-based (PET/CT, PET/MRI) measurements with a suitable tracer can place therapeutic decisions on a reliable basis. We present the clinical significance of amino acid-PET-based hybrid nuclear medicine imaging studies in the therapeutic management of these patients by reviewing the literature data on the practice of the method in Hungary and abroad and presenting the results of our retrospective summary research so far. Orv Hetil. 2023; 164(32): 1247-1255.

Evaluation of Lens Doses among Medical Staff Involved in Nuclear Medicine: Current Eye Radiation Exposure among Nuclear-Medicine Staff

The International Commission on Radiological Protection has lowered the annual equivalent eye-lens dose to 20 mSv. Although occupational exposure can be high in nuclear medicine (NM) departments, few studies have been conducted regarding eye-lens exposure among NM staff. This study aimed to estimate the annual lens doses of staff in an NM department and identify factors contributing to lens exposure. Four nurses and six radiographers performing positron emission tomography (PET) examinations and four radiographers performing radioisotope (RI) examinations (excluding PET) were recruited for this study. A lens dosimeter was attached near the left eye to measure the 3-mm-dose equivalent; a personal dosimeter was attached to the left side of the neck to measure the 1-cm- and 70-µm-dose equivalents. Measurements were acquired over six months, and the cumulative lens dose was doubled to derive the annual dose. Correlations between the lens and personal-dosimeter doses, between the lens dose and the numbers of procedures, and between the lens dose and the amounts of PET drugs (radiopharmaceuticals) injected were examined. Wilcoxon’s signed-rank test was used to compare lens and personal-dosimeter doses. The estimated annual doses were 0.93 ± 0.13 mSv for PET nurses, 0.71 ± 0.41 mSv for PET radiographers, and 1.10 ± 0.53 mSv for RI radiographers. For PET nurses, but not for PET or RI radiographers, there was a positive correlation between the numbers of procedures and lens doses and between amounts injected and lens doses. There was a significant difference between the lens and personal-dosimeter doses of PET nurses. The use of protective measures, such as shielding, should prevent NM staff from receiving lens doses &gt; 20 mSv/year. However, depending on the height of the protective shield, PET nurses may be unable to assess the lens dose accurately using personal dosimeters.

3D melanoma spheroid model for the development of positronium biomarkers

It was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium imaging utilizes the properties of positronium atoms, which are built from the electrons and positrons produced in the body during PET examinations. We hypothesized that positronium imaging would be sensitive to the in vitro discrimination of tumor-like three-dimensional structures (spheroids) built of melanoma cell lines with different cancer activities and biological properties. The lifetime of ortho-positronium (o-Ps) was evaluated in melanoma spheroids from two cell lines (WM266-4 and WM115) differing in the stage of malignancy. Additionally, we considered parameters such as the cell number, spheroid size and melanoma malignancy to evaluate their relationship with the o-Ps lifetime. We demonstrate pilot results for o-Ps lifetime measurement in extracellular matrix-free spheroids. With the statistical significance of two standard deviations, we demonstrated that the higher the degree of malignancy and the rate of proliferation of neoplastic cells, the shorter the lifetime of ortho-positronium. In particular, we observed the following indications encouraging further research: (i) WM266-4 spheroids characterized by a higher proliferation rate and malignancy showed a shorter o-Ps lifetime than WM115 spheroids characterized by a lower growth rate. (ii) Both cell lines showed a decrease in the lifetime of o-Ps after spheroid generation on day 8 compared to day 4 in culture, and the mean o-Ps lifetime was longer for spheroids formed from WM115 cells than for those formed from WM266-4 cells, regardless of spheroid age. The results of this study revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.

Brain exposure of osimertinib in patients with epidermal growth factor receptor mutation non-small cell lung cancer and brain metastases: A positron emission tomography and magnetic resonance imaging study.

Brain metastases (BMs) are associated with poor prognosis in epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). Osimertinib is a third-generation, irreversible, EGFR-tyrosine kinase inhibitor that potently and selectively inhibits EGFR-sensitizing and T790M resistance mutations with efficacy in EGFRm NSCLC including central nervous system (CNS) metastases. The open-label phase I positron emission tomography (PET) and magnetic resonance imaging (MRI) study (ODIN-BM) assessed [11 C]osimertinib brain exposure and distribution in patients with EGFRm NSCLC and BMs. Three dynamic 90-min [11 C]osimertinib PET examinations were acquired together with metabolite-corrected arterial plasma input functions at: baseline, after first oral osimertinib 80 mg dose, and after greater than or equal to 21 days of osimertinib 80 mg q.d. treatment. Contrast-enhanced MRI was performed at screening and after 25-35 days of osimertinib 80 mg q.d.; treatment effect was assessed per CNS Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and per volumetric changes in total BM using a novel analysis approach. Four patients (aged 51-77 years) completed the study. At baseline, ~1.5% injected radioactivity reached the brain (IDmax[brain] ) 22 min (median, Tmax[brain] ) after injection. Total volume of distribution (VT ) in whole brain was numerically higher compared with the BM regions. After a single oral osimertinib 80 mg dose, there was no consistent decrease in VT in whole brain or BMs. After greater than or equal to 21 days' daily treatment, VT in whole brain and BMs were numerically higher versus baseline. MRI revealed 56%-95% reduction in total BMs volume after 25-35 days of osimertinib 80 mg q.d. treatment. The [11 C]osimertinib crossed the blood-brain and brain-tumor barriers and had a high, homogeneous brain distribution in patients with EGFRm NSCLC and BMs.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.

Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.

Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8 to 16 years post-PET scan, in social drinkers. Longitudinal study investigating the association between PET data and later self-report measures in healthy individuals. Academic research imaging centre in Stockholm, Sweden. There were 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies. One PET examination with the D2R antagonist radioligand [11 C]raclopride at baseline and self-report measures assessing alcohol use, drug use, impulsivity, reward sensitivity and family history of alcohol or substance use disorder at follow-up. We found no evidence for an association between D2R availability and later alcohol use (B = -0.019, B 95% CI = -0.043 to -0.006, P = 0.147) nor for the majority of the alcohol-related factors (B 95% CI = -0.034 to 0.004, P = 0.273-0.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = -0.017, B 95% CI = -0.034 to -0.001, P = 0.046). Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.

In Vivo Preclinical Assessment of β-Amyloid-Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer's Disease-Resembling Hypercholesterinaemic Rat Model.

Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer's disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model-with the involvement of 8 week and 48 week-old Fischer-344 rats-by Al administration for the safe and rapid verification of β-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and β-amyloid-affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development.

Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer’s disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A+) and tau PET-positive (T+) in the medial temporal lobe (A+TMTL+) and/or in the temporal neocortex (A+TNEO-T+) and compared them with A+T− and A−T− groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A+TNEO-T+ (hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9–33.7), A+TMTL+ (HR = 14.6, 95% CI = 8.1–26.4) and A+T− (HR = 2.4, 95% CI = 1.4–4.3) groups versus the A−T− (reference) group. Both A+TMTL+ (HR = 6.0, 95% CI = 3.4–10.6) and A+TNEO-T+ (HR = 7.9, 95% CI = 4.7–13.5) groups also showed faster clinical progression to mild cognitive impairment than the A+T− group. Linear mixed-effect models indicated that the A+TNEO-T+ (β = −0.056 ± 0.005, T = −11.55, P < 0.001), A+TMTL+ (β = −0.024 ± 0.005, T = −4.72, P < 0.001) and A+T− (β = −0.008 ± 0.002, T = −3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A−T− (reference) group (all P < 0.001). Both A+TNEO-T+ (P < 0.001) and A+TMTL+ (P = 0.002) groups also progressed faster than the A+T− group. In summary, evidence of advanced Alzheimer’s disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3–5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.

Oncology and cardiology positron emission tomography/computed tomography faced with COVID-19: A review of available literature data.

The COVID-19 pandemic has forced people to significantly change their lifestyles and attitudes, and has greatly burdened healthcare delivery systems worldwide. The redistribution of the medical delivery system to maintain normal medical care while responding generously to COVID-19 is a continuing challenge that weighs heavily on medical institutions. Among imaging modalities, chest X-rays and computed tomography (CT) examinations have clearly made a large contribution to treatment of COVID-19. In contrast, it is difficult to express the standpoint of nuclear medicine examinations in a straightforward manner, as the greatest emphasis in this modality has been on how necessary medical care can continue to be provided. Many clinical reports of nuclear medicine examinations related to COVID-19 have been published, and knowledge continues to accumulate. This review provides a summary of the current state of oncology and cardiology positron emission tomography (PET) examinations related to COVID-19, and includes preparation of the nuclear medicine department, trends in PET examinations, specific imaging findings on 18F-fluorodeoxyglucose (FDG) PET/CT, imaging of complications of COVID-19, PET tracers other than FDG, and the effects of vaccines on PET imaging findings.

The Efficacy of Trabecular Titanium Cages to Induce Reparative Bone Activity after Lumbar Arthrodesis Studied through the 18f-Naf PET/CT Scan: Observational Clinical In-Vivo Study.

Background: Titanium trabecular cages (TTCs) are emerging implants designed to achieve immediate and long-term spinal fixation with early osseointegration. However, a clear radiological and clinical demonstration of their efficacy has not yet been obtained. The purpose of this study was to evaluate the reactive bone activity of adjacent plates after insertion of custom-made titanium trabecular cages for the lumbar interbody with positron emission tomography (PET)/computed tomography (CT) 18F sodium fluoride (18F-NaF). Methods: This was an observational clinical study that included patients who underwent surgery for degenerative disease with lumbar interbody fusion performed with custom-made TTCs. Data related to the metabolic-reparative reaction following the surgery and its relationship with clinical follow-up from PET/CT performed at different weeks were evaluated. PET/CTs provided reliable data, such as areas showing abnormally high increases in uptake using a volumetric region of interest (VOI) comprising the upper (UP) and lower (DOWN) limits of the cage. Results: A total of 15 patients was selected for PET examination. Timing of PET/CTs ranged from one week to a maximum of 100 weeks after surgery. The analysis showed a negative correlation between the variables SUVmaxDOWN/time (r = −0.48, p = 0.04), ratio-DOWN/time (r = −0.53, p = 0.02), and ratio-MEAN/time (r = −0.5, p = 0.03). Shapiro−Wilk normality tests showed significant results for the variables ratio-DOWN (p = 0.002), ratio-UP (0.013), and ratio-MEAN (0.002). Conclusions: 18F-NaF PET/CT has proven to be a reliable tool for investigating the metabolic-reparative reaction following implantation of TTCs, demonstrating radiologically how this type of cage can induce reparative osteoblastic activity at the level of the vertebral endplate surface. This study further confirms how electron-beam melting (EBM)-molded titanium trabecular cages represent a promising material for reducing hardware complication rates and promoting fusion.

Clinical Applications of PSMA PET Examination in Patients with Prostate Cancer.

Simple SummaryThe prostate specific membrane antigens, abbreviated as PSMAs, are type II membrane proteins that are highly ex-pressed on the surface of malignant prostate tissue in prostate cancer (PCa), particularly in aggressive, andro-gen-deprived, metastatic, and hormone-refractory PCa. Today, radionuclides that bind to these PSMA peptides are widely available for diagnostic and therapeutic purposes to specifically image and target prostate tumor cells at molec-ular level. In this descriptive review, we aimed to emphasize the usefulness of PSMA positron emission tomography (PET) examination in the management of patients with various stages of PCa. In addition, we outlined the main pitfalls and limitations of this scan to avoid misinterpretation of the results and to improve the decision making process in rela-tion to the patient’s further treatment. We concluded that PSMA PET examination in primary PCa patients has an es-sential role in the high-risk group. It is the new imaging standard in patients with in biochemical recurrence PCa and plays an important role in treatment decision. Furthermore, PSMA PET scan is a gold standard for the evaluation of PSMA targeted therapies in patients having progress of the disease. Future prospective studies, particularly on the im-pact of PSMA PET on therapy stratification, may further strengthen the role of PSMA in the treatment of PCa patients. With the progressive aging of the population in industrially developed countries, as well as advances in diagnostic and biopsy techniques and improvements in patient awareness, the incidence of prostate cancer (PCa) is continuously increasing worldwide. Therefore, PCa is currently considered as the second leading cause of tumor-related death. Early detection of the tumor and its metastasis is essential, as the rate of disease recurrence is high and occurs in 27% to 53% of all patients who underwent curative therapy with radical prostatectomy or local radiotherapy. In this regard, the prostate specific membrane antigens, abbreviated as PSMAs, are type II membrane proteins that are highly expressed on the surface of malignant prostate tissue in PCa, particularly in aggressive, androgen-deprived, metastatic, and hormone-refractory PCa, and they are inversely associated with the androgen level. Up to 95% of adenocarcinomas of the prostate express PSMA receptors on their surface. Today, radionuclides that bind to these PSMA peptides are widely accepted for diagnostic and therapeutic purposes to specifically image and target prostate tumor cells at the molecular level, a process referred to as targeted theranostics. Numerous studies have demonstrated that the integration of these peptides into diagnostic and therapeutic procedures plays a critical role in the primary staging and treatment decisions of especially high-risk PCa, expands therapeutic options for patients with advanced stage of prostate tumor, and prolongs patients’ survival rate. In this review article, we intend to briefly spotlight the latest clinical utilization of the PSMA-targeted radioligand PET imaging modality in patients with different stages of PCa. Furthermore, limitations and pitfalls of this diagnostic technique are presented.

PET/NIR-II fluorescence imaging and image-guided surgery of glioblastoma using a folate receptor α-targeted dual-modal nanoprobe.

The surgery of glioblastoma (GBM) requires a maximal resection of the tumor when it is safe and feasible. The infiltrating growth property of the GBM makes it a challenge for neurosurgeons to identify the tumor tissue even with the assistance of the surgical microscope. This highlights the urgent requirement for imaging techniques that can differentiate tumor tissues during surgery in real time. Fluorescence image-guided surgery of GBM has been investigated using several non-specific fluorescent probes that emit light in the visible and the first near-infrared window (NIR-I, 700-900nm), which limit the detection accuracy because of the non-specific targeting mechanism and spectral characteristics. Targeted NIR-II (1000-1700nm) fluorescent probes for GBM are thus highly desired. The folate receptor (FR) has been reported to be upregulated in GBM, which renders it to be a promising target for specific tumor imaging. In this study, the folic acid (FA) that can target the FR was conjugated with the clinically approved indocyanine green (ICG) dye and DOTA chelator for radiolabeling with 64Cu to achieve targeted positron emission tomography (PET) and fluorescence imaging of GBM. Surprisingly it was found that the resulted bioconjugate, DOTA-FA-ICG and non-radioactive natCu-DOTA-FA-ICG, were both self-assembled into nanoparticles with NIR-II emission signal. The radiolabeled DOTA-FA-ICG, 64Cu-DOTA-FA-ICG, was found to specifically accumulate in the orthotopic GBM models using in vivo PET, NIR-II, and NIR-I fluorescence imaging. The best time window of fluorescence imaging was demonstrated to be 24h after DOTA-FA-ICG injection. NIR-II fluorescence image-guided surgery was successfully conducted in the orthotopic GBM models using DOTA-FA-ICG. All the fluorescent tissue was removed and proved to be GBM by the H&E examination. Overall, our study demonstrates that the probes, 64Cu-DOTA-FA-ICG and DOTA-FA-ICG, hold promise for preoperative PET examination and intraoperative NIR-II fluorescence image-guided surgery of GBM, respectively.

Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [18 F]FMPEP-d2.

ABSTRACTBackgroundThe endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD).ObjectiveThe aim of this study was to investigate CB1 receptors in PD with [18F]FMPEP‐d 2 positron emission tomography (PET) and the effect of dopaminergic medication on the [18F]FMPEP‐d 2 binding.MethodsThe data consisted of 16 subjects with PD and 10 healthy control subjects (HCs). All participants underwent a [18F]FMPEP‐d 2 high‐resolution research tomograph PET examination for the quantitative assessment of cerebral binding to CB1 receptors. To investigate the effect of dopaminergic medication on the [18F]FMPEP‐d 2 binding, 15 subjects with PD underwent [18F]FMPEP‐d 2 PET twice, both on and off antiparkinsonian medication.Results[18F]FMPEP‐d 2 distribution volume was significantly lower in the off scan compared with the on scan in basal ganglia, thalamus, hippocampus, and amygdala (P < 0.05). Distribution volume was lower in subjects with PD off than in HCs globally (P < 0.05), but not higher than in HCs in any brain region.ConclusionsSubjects with PD have lower CB1 receptor availability compared with HCs. PD medication increases CB1 receptor toward normal levels. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Development and technical validation of an ultrasound nebulizer to deliver intraperitoneal pressurized aerosols in a rat colon cancer peritoneal metastases model

Background/aimTo develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model.Material and methodsFor aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy.ResultsThe USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 μm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1–2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals.ConclusionsThe USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.

Prognostic utility of longitudinal quantification of PET myocardial blood flow early post heart transplantation

BackgroundMyocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation. Methods and ResultHeart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes. ConclusionLow-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT.

Processing speed dysfunction is associated with functional corticostriatal circuit alterations in childhood epilepsy with centrotemporal spikes: a PET and fMRI study

PurposeEpilepsy with centrotemporal spikes (ECTS) is the most common epilepsy syndrome in children and usually presents with cognitive dysfunctions. However, little is known about the processing speed dysfunction and the associated neuroimaging mechanism in ECTS. This study aims to investigate the brain functional abnormality of processing speed dysfunction in ECTS patients by using the 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI).MethodsThis prospective study recruited twenty-eight ECTS patients who underwent the 18F-FDG PET, rs-fMRI, and neuropsychological examinations. Twenty children with extracranial tumors were included as PET controls, and 20 healthy children were recruited as MRI controls. The PET image analysis investigated glucose metabolism by determining standardized uptake value ratio (SUVR). The MRI image analysis explored abnormal functional connectivity (FC) within the cortical–striatal circuit through network-based statistical (NBS) analysis. Correlation analysis was performed to explore the relationship between SUVR, FC, and processing speed index (PSI).ResultsCompared with healthy controls, ECTS patients showed normal intelligence quotient but significantly decreased PSI (P = 0.04). PET analysis showed significantly decreased SUVRs within bilateral caudate, putamen, pallidum, left NAc, right rostral middle frontal gyrus, and frontal pole of ECTS patients (P < 0.05). Rs-fMRI analysis showed absolute values of 20 FCs were significantly decreased in ECTS patients compared with MRI controls, which connected 16 distinct ROIs. The average SUVR of right caudate and the average of 20 FCs were positively correlated with PSI in ECTS patients (P = 0.034 and P = 0.005, respectively).ConclusionThis study indicated that ECTS patients presented significantly reduced PSI, which is closely associated with decreased SUVR and FC of cortical–striatal circuit. Caudate played an important role in processing speed dysfunction.Clinical trial registrationNCT04954729; registered on July 8, 2021, public site, https://clinicaltrials.gov/ct2/show/NCT04954729