[Application of micro-bolus injection and piezoelectric sensors to improve the safety of radiopharmaceuticals bolus injection].

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.

[223Ra] RaCl2 nanomicelles showed potent effect against osteosarcoma: targeted alpha therapy in the nanotechnology era.

The treatment of bone metastatsis as primary bone cancer itself is still a challenge. The use od radium dichloride ([223Ra] RaCl2) has emerged in the last few years as one of the best treatment choice for bone cancer, with especial focus in bone metastasis. The alpha-emitter radiopharmaceutical has showed potent and efficient results in several clinical trials. In this study we have formulated radium dichloride ([223Ra] RaCl2) nanomicelles in order to evaluate and compare with pure radium dichloride ([223Ra] RaCl2). The results showed that nanomicelles at the same dose had a superior effect (20% higher efficient) when compared with pure radium dichloride ([223Ra] RaCl2). The results corroborated the effectiveness of the nanosystem validating the application of nanotechnology in alpha-radiotherapy with radium dichloride ([223Ra] RaCl2).

Total Variation Constrained Graph Manifold Learning Strategy for Cerenkov Luminescence Tomography.

Harnessing the power and flexibility of radiolabeled molecules, Cerenkov luminescence tomography (CLT) provides a novel technique for non-invasive visualisation and quantification of viable tumour cells in a living organism. However, owing to the photon scattering effect and the ill-posed inverse problem, CLT still suffers from insufficient spatial resolution and shape recovery in various preclinical applications. In this study, we proposed a total variation constrained graph manifold learning (TV-GML) strategy for achieving accurate spatial location, dual-source resolution, and tumour morphology. TV-GML integrates the isotropic total variation term and dynamic graph Laplacian constraint to make a trade-off between edge preservation and piecewise smooth region reconstruction. Meanwhile, the tetrahedral mesh-Cartesian grid pair method based on the k-nearest neighbour, and the adaptive and composite Barzilai-Borwein method, were proposed to ensure global super linear convergence of the solution of TV-GML. The comparison results of both simulation experiments and in vivo experiments further indicated that TV-GML achieved superior reconstruction performance in terms of location accuracy, dual-source resolution, shape recovery capability, robustness, and in vivo practicability. Significance: We believe that this novel method will be beneficial to the application of CLT for quantitative analysis and morphological observation of various preclinical applications and facilitate the development of the theory of solving inverse problem.

El papel pronóstico del SUVmáx basal y cambio del SUVmáx en la PET/TC con18F-FDG en pacientes con cáncer de mama con ganglios positivos que reciben quimioterapia neoadyuvante / The prognostic role of baseline 18F-FDG PET/CT SUVmax and SUVmax change in patients with node-positive breast cancer receiving neoadjuvant chemotherapy

Objetivo: En este estudio, se tuvo como objetivo determinar el papel pronóstico del valor de captación máximo estandarizado (SUVmáx) basal obtenido por PET/TC antes del tratamiento, y el cambio en el SUVmáx (ΔSUVmáx [%]) en pacientes con cáncer de mama con ganglios linfáticos axilares positivos en tratamiento con quimioterapia neoadyuvante (NAC).Métodos: Se evaluaron en el estudio 180 pacientes con SUVmáx basal y 121 pacientes con medición de SUVmáx después del tratamiento. Se midieron el valor de SUVmáx inicial de la mama (SUVmáxBI) y axila (SUVmáxAI), y el cambio en el SUVmáx de la mama (ΔSUVmáxB) y axila (ΔSUVmáxA). El valor de corte óptimo de SUVmáx y ΔSUVmáx se determinó mediante el análisis de la curva ROC. La supervivencia libre de enfermedad (SSE) y la supervivencia global (SG) se calcularon mediante curvas de Kaplan-Meier.Resultados: Se encontró que los parámetros ΔSUVmáxB, pCRB, pCRA y pCR se asociaron con la recaída (p <0.001, p =0.033, p =0.016 y p =0.013, respectivamente). ΔSUVmáxB y SUVmáxAI se asociaron con la mortalidad (p=0,001 y p=0,006, respectivamente). El análisis de regresión de Cox múltiple reveló que el valor de ΔSUVmáxB era un factor pronóstico independiente para la recaída y la mortalidad (p = 0,013 y p = 0,010, respectivamente).Conclusión: Los resultados muestran que ΔSUVmáxB es un factor pronóstico independiente de recaída y mortalidad en pacientes con cáncer de mama con ganglios linfáticos axilares positivos que recibieron NAC (AU)

Objective: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC).Methods: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves.Results: ΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively).Conclusion: The results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC (AU)

Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs.

Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a "theranostic pair" imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical. However, theranostic dosimetry assumes that the pharmacokinetics and biodistributions of both radiopharmaceuticals in the pair are identical or very similar, an assumption that still requires further validation for many theranostic pairs. In this review, we consider both same-element and different-element theranostic pairs and attempt to determine if factors exist which may cause inaccurate dose extrapolations in theranostic dosimetry, either intrinsic (e.g. chemical differences) or extrinsic (e.g. injecting different amounts of each radiopharmaceutical) to the radiopharmaceuticals. We discuss the basis behind theranostic dosimetry and present common theranostic pairs and their therapeutic applications in oncology. We investigate general factors that could create alterations in the behavior of the radiopharmaceuticals or the quantitative accuracy of imaging them. Finally, we attempt to determine if there is evidence showing some specific pairs as suitable for theranostic dosimetry. We show that there are a variety of intrinsic and extrinsic factors which can significantly alter the behavior among pairs of radiopharmaceuticals, even if they belong to the same chemical element. More research is needed to determine the impact of these factors on theranostic dosimetry estimates and on patient outcomes, and how to correctly account for them.

Malignant prediction of incidental findings using ring-type dedicated breast positron emission tomography.

The classification according to uptake patterns and metabolic parameters on ring-type dedicated breast positron emission tomography (dbPET) is useful for detecting breast cancer. This study investigated the performance of dbPET for incidental findings that were not detected by mammography and ultrasonography. In 1,076 patients with breast cancer who underwent dbPET, 276 findings were incidentally diagnosed before treatment. Each finding was categorized as focus (uptake size ≤ 5 mm), mass (> 5 mm), or non-mass (multiple uptake) according to uptake patterns. Non-mass uptakes were additionally classified based on their distributions as-linear, focal, segmental, regional, or diffuse. Thirty-two findings (11.6%) were malignant and 244 (88.4%) were benign. Visually, 227 (82.3%) findings were foci, 7 (2.5%) were masses, and 42 (15.2%) were non-masses. Malignant rates of focus, mass, and non-mass were 9.7%, 28.6%, and 19.0%, respectively. In the non-mass findings, 23 were regional and diffuse distributions, and presented as benign lesions. Focus uptake with low lesion-to-background ratio (LBR) and no hereditary risk were relatively low (2.7%) in breast cancer. In multivariate analysis, LBR and hereditary risk were significantly associated with breast cancer (p = 0.006 and p = 0.013, respectively). Uptake patterns, LBR, and hereditary risk are useful for predicting breast cancer risk in incidental dbPET findings.

Dosing Therapeutic Radiopharmaceuticals in Obese Patients.

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.

Radiosynthesis of a novel antisense imaging probe targeting LncRNA HOTAIR in malignant glioma.

BACKGROUND: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. METHODS: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. RESULTS: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. CONCLUSION: The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

Synthesis and biological evaluation of novel PET tracers [18F]AG120 & [18F]AG135 for imaging mutant isocitrate dehydrogenase 1 expression.

Mutations in isocitrate dehydrogenase 1 (IDH1) are commonly found in various human malignancies. Inhibitors of several mutant IDH1 enzymes have entered clinical trials as target therapeutic drugs for the treatment of patients with IDH1 mutations. Herein, we report the synthesis and evaluation of two 18F-labeled tracers, [18F]AG120 and [18F]AG135 for imaging expression of mutated IDH1 in positron emission tomography (PET). [18F]AG120 and [18F]AG135 were synthesized in decay-corrected radiochemical yield of 1 % and 3 %, respectively, high molar activity (52-66 MBq/nmol and 216-339 MBq/nmol, respectively) and high radiochemical purity (>99%). Both tracers showed good in vitro stability, selective uptake into mutated IDH1-expressing cells and good pharmacokinetic profiles with low uptake in most organs/tissues. Furthermore, [18F]AG120 micro-PET/CT imaging displayed significantly greater uptake in IDH1-mutant than in wild-type tumors, Relatively, uptake of [18F]AG135 was observed neither in IDH1-mutant tumor xenografts nor in wild-type tumors. This study suggests that [18F]AG120 is a promising radiotracer for PET imaging of IDH1 mutation, However, further optimization and investigation are necessary for [18F]AG135 due to the limited uptake in mutated IDH1-expressing tumors.

Neuronal PET tracers for Alzheimer's disease.

Advancements in brain imaging techniques have emerged as a significant tool in detecting Alzheimer's disease (AD) progression. The complicated cascade of AD progression can be detected using radio imaging, especially with Positron emission tomography (PET). The review focus on recently introduced investigational PET tracers targeting neurofibrillary tau aggregates found typically in AD. Herein, we also address the use of different PET tracers and the clinical implementation of established and newer generation tracers. This review also intends to discuss the importance of several PET radiotracers and challenges in PET imaging.

A cost-utility analysis of 18F-fluorocholine-positron emission tomography imaging for localizing primary hyperparathyroidism in the United States.

BACKGROUND: Primary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States. METHODS: A decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed. RESULTS: Positron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy. CONCLUSION: Our model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations.

Correlation of Preoperative Imaging Findings and Parathyroidectomy Outcomes Support NICE 2019 Guidance.

CONTEXT: Preoperative localization studies are standard practice in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT). The most common modalities are neck ultrasound (US) and sestamibi scanning. However, the nature of pHPT is changing, with imaging increasingly yielding negative results. Numerous studies suggest unlocalized disease is associated with poor outcomes, calling into question whether such patients are best treated conservatively. OBJECTIVE: This study aims to correlate parathyroidectomy outcomes with preoperative imaging in a single, high-volume institution. METHODS: Data from a prospectively maintained departmental database of operations performed from 2017 to 2019 were analyzed. All patients undergoing first-time surgery for sporadic pHPT were included. Data collected included patient demographics, preoperative imaging, surgical strategy, and postoperative outcomes. RESULTS: A total of 609 consecutive parathyroidectomies were included, with a median age of 59 years (range 20-87 years). The all-comer cure rate was 97.5%; this was 97.9% in dual localized patients (those with positive US and sestamibi), compared to 95.8% in the dual unlocalized group (those with negative US and sestamibi) (P = 0.33). Unilateral neck exploration was the chosen approach in 59.9% of patients with double-positive imaging and 5.7% of patients with double-negative imaging (otherwise, bilateral parathyroid visualization was performed). There was no significant difference in postoperative complications between patients undergoing unilateral or bilateral neck exploration. CONCLUSIONS: Patients with negative preoperative imaging who undergo parathyroidectomy are cured in almost 96% of cases, compared to 98% when the disease is localized. This difference does not reach statistical or clinical significance. These findings therefore support current recommendations that all patients with pHPT who are likely to benefit from operative intervention should be considered for parathyroidectomy, irrespective of preoperative imaging findings.

ANALGESIC EFFECT OF VARIOUS RADIOPHARMACEUTICALS IN THE COMPLEX TREATMENT OF METASTATIC BONE DISEASE. / ZNEBOLIuVAL'NYI VPLYV RIZNYKh RADIOFARMPREPARATIV U KOMPLEKSNOMU LIKUVANNI METASTATYChNOGO URAZhENNIa KISTOK.

OBJECTIVE: The study objective was to investigate and compare the effectiveness of different radiopharmaceuticalsin the treatment of metastatic bone disease. MATERIALS AND METHODS: Cancer patients (n = 150, average age (55 ± 11.6) years, 95 females, 55 males) having gotvarious primary tumors and metastatic bone disease were given medical treatment at the Department of NuclearMedicine of the National Institute of Cancer. The 153Sm, 32Р, and 89Sr radiopharmaceutical agents produced by the«Radiopreparats¼ enterprise (Republic of Uzbekistan) and Radioisotope Centre Polatom (National Centre for NuclearResearch, Poland) were administered to the patients. There were cases of breast cancer (n = 75), prostate cancer(n = 45), lung cancer (n = 10), kidney cancer (n = 4), cervical cancer (n = 5), and rectosigmoid cancer (n = 11) amongthe treated subjects. In 135 patients (90 %) the bone metastases were detected by osteoscintigraphy with 99мTc- mo-nodiphosphonate. In 15 cases the diagnosis of metastatic bone disease was verified by other radiology methods. RESULTS: The pain intensity rating scale (LACOMED) was used to assay the analgesic effect of various radiopharma-ceuticals in metastatic bone disease. Results of treatment with 32P, 89Sr, and 153Sm were included in a comparativeanalysis procedure. It was established that the level of pain syndrome ranged from 7-8 points on the LACOMED scalebefore treatment. Upon administration of radionuclide therapy the level of pain was reduced down to 3-5 points,namely with 32P therapy it has decreased by 30.7 %, with 89Sr by 33.2 %, and with 153Sm by 41.5 % respectively. Timepattern of 153Sm analgesic effectiveness was studied depending on the number of treatment sessions. The best valueof analgesic effect of 153Sm was registered after the first treatment session with a tendency to decrease after the sec-ond and significantly lower analgesic effects after the third session. Tolerance of 153Sm was rated on the CTCNCA (v)4.3 scale. The best tolerance was peculiar to 153Sm corresponding to the «good¼ level according to a point assess-ment. When using 89Sr the drug tolerance was lower, not requiring however the drug discontinuation. The 32P radio-pharmaceutical featured the lowest tolerance approaching the «satisfactory¼ rating. In 11 patients upon that theside effects were found significantly impairing the patient's status, accordingly some extra measures were required.No decision to cancel the drug administration was made. CONCLUSIONS: Radionuclide therapy with 153Sm-oxabiphor agent can be used in the complex treatment of metastat-ic bone disease in cancer patients having got tumors of different localization. 153Sm-oxabiphor is the most effectiveand best tolerable radiopharmaceutical agent in the pain treatment in metastatic bone disease in comparison with32P and 89Sr preparations (р < 0.05).

Data-driven identification of diagnostically useful extrastriatal signal in dopamine transporter SPECT using explainable AI.

This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter SPECT with 123I-FP-CIT in parkinsonian syndromes. A total of 1306 123I-FP-CIT-SPECT were included retrospectively. Binary classification as 'reduced' or 'normal' striatal 123I-FP-CIT uptake by an experienced reader served as standard-of-truth. A custom-made 3-dimensional convolutional neural network (CNN) was trained for classification of the SPECT images with 1006 randomly selected images in three different settings: "full image", "striatum only" (3-dimensional region covering the striata cropped from the full image), "without striatum" (full image with striatal region removed). The remaining 300 SPECT images were used to test the CNN classification performance. Layer-wise relevance propagation (LRP) was used for voxelwise quantification of the relevance for the CNN-based classification in this test set. Overall accuracy of CNN-based classification was 97.0%, 95.7%, and 69.3% in the "full image", "striatum only", and "without striatum" setting. Prominent contributions in the LRP-based relevance maps beyond the striatal signal were detected in insula, amygdala, ventromedial prefrontal cortex, thalamus, anterior temporal cortex, superior frontal lobe, and pons, suggesting that 123I-FP-CIT uptake in these brain regions provides clinically useful information for the differentiation of neurodegenerative and non-neurodegenerative parkinsonian syndromes.

Synthesis and Screening in Mice of Fluorine-Containing PET Radioligands for TSPO: Discovery of a Promising 18F-Labeled Ligand.

Translocator protein 18 kDa (TSPO) is a biomarker of neuroinflammation. [11C]ER176 robustly quantifies TSPO in the human brain with positron emission tomography (PET), irrespective of subject genotype. We aimed to develop an ER176 analog with potential for labeling with longer-lived fluorine-18 (t1/2 = 109.8 min). New fluoro and trifluoromethyl analogs of ER176 were prepared through a concise synthetic strategy. These ligands showed high TSPO affinity and low human genotype sensitivity. Each ligand was initially labeled by a generic 11C-methylation procedure, thereby enabling speedy screening in mice. Each radioligand was rapidly taken up and well retained in the mouse brain at baseline after intravenous injection. Preblocking of TSPO showed that high proportions of brain uptake were specifically bound to TSPO at baseline. Overall, the 3-fluoro analog of [11C]ER176 ([11C]3b) displayed the most promising imaging properties. Therefore, a method was developed to label 3b with [18F]fluoride ion. [18F]3b gave similarly promising PET imaging results and deserves evaluation in higher species.

Total lesion glycolysis as a predictor of clinical T3-4a laryngeal cancer with laryngectomy or nonlaryngectomy.

ABSTRACT: The purpose of the present study is to investigate whether the 18F-fluorodeoxyglucose (18F-FDG) uptake parameter is related to survival outcomes for patients with clinical T3-T4a laryngeal cancer with various definitive treatments including total laryngectomy (TL). Parameters of 18F-FDG uptake in the primary tumors of 46 cases which were assessed by positron emission tomography with computed tomography were enrolled in the present observation study. Monovariate or multivariate survival analyses were performed with log-rank test or Cox regression model, with the hazard ratio (HR) and 95% confidence interval (CI), respectively. Cutoff values of the 18F-FDG uptake parameters were determined by the lowest P-value for monovariate overall survival. In the monovariate analysis, both metabolic tumor volume ≥13.1 and total lesion glycolysis (TLG) ≥46.5 were significantly associated with shorter overall survival, and TLG ≥46.5 was also related to a reduction in distant metastasis-free survival. In the multivariate analysis adjusting for clinical T classification (cT4/cT3) and treatment group (TL/non-TL), TLG (≥46.5/<46.5) was associated with both poorer overall (HR: 3.16, 95% CI: 1.10-9.49) and distant metastasis-free (HR: 8.91, 95% CI: 1.93-62.6) survival. In conclusion, TLG is a predictor for survival in laryngeal cancer.

Impact of PET/CT among patients with suspected mycotic aortic aneurysms.

PURPOSE: To determine the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) on clinical management in patients with suspected mycotic aortic aneurysms (MAA). MATERIALS AND METHODS: For this observational cohort study 101 PET/CT were acquired in 50 patients, thereof 50 for the initial diagnosis/baseline scan, 51 for follow-up. Impact on patient management was defined in three categories: PET/CT results were "confirmed" (by clinical follow-up), "suspected" (conclusive, not confirmed), or "misleading" (proven wrong by follow-up). For clinical follow-up patient data were recorded at the time of imaging, and at the latest recorded clinical visit. It included patient demographics, clinical information, laboratory data, results of microbiology and other diagnostic procedures, information about treatment, and patient's general health condition. RESULTS: In four patients (8%) no clinical follow-up was feasible, the other 46 patients were clinically followed for a median of 898 days (IQR 320-4105). The combined evaluation of all 101 PET/CT demonstrated an impact on patient management in 78,5% of cases (48,5% confirmed, 30% suspected). Results of 21,5% of the PET/CT examinations were misleading. Respective values at baseline and at follow-up were: impact on patient management in 82% and 74,5% (70% and 27.5% confirmed, and 12% and 47% suspected), misleading cases in 18% and 25.5%. CONCLUSION: In MAA, PET/CT has a high impact on patient management, which is more pronounced with baseline than with follow-up examinations. However, PET/CT results may be misleading in a smaller proportion of cases.

Application of FLIC model to predict adverse events onset in neuroendocrine tumors treated with PRRT.

To develop predictive models of side effect occurrence in GEPNET treated with PRRT. Metastatic GEPNETs patients treated in our centre with PRRT (177Lu-Oxodotreotide) from 2019 to 2020 were considered. Haematological, liver and renal toxicities were collected and graded according to CTCAE v5. Patients were grouped according with ECOG-PS, number of metastatic sites, previous treatment lines and therapies received before PRRT. A FLIC model with backward selection was used to detect the most relevant predictors. A subsampling approach was implemented to assess variable selection stability and model performance. Sixty-seven patients (31 males, 36 females, mean age 63) treated with PRRT were considered and followed up for 30 weeks from the beginning of the therapy. They were treated with PRRT as third or further lines in 34.3% of cases. All the patients showed at least one G1-G2, meanwhile G3-G5 were rare events. No renal G3-G4 were reported. Line of PRRT administration, age, gender and ECOG-PS were the main predictors of haematological, liver and renal CTCAE. The model performance, expressed by AUC, was > 65% for anaemia, creatinine and eGFR. The application of FLIC model can be useful to improve GEPNET decision-making, allowing clinicians to identify the better therapeutic sequence to avoid PRRT-related adverse events, on the basis of patient characteristics and previous treatment lines.