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1.
Pitfalls and Misinterpretations of Cardiac Findings on PET/CT Imaging: A Careful Look at the Heart in Oncology Patients.
Betancourt Cuellar, SL, Palacio, D, Benveniste, MF, Carter, BW, Gladish, G
Current problems in diagnostic radiology. 2019;(2):172-183
Abstract
Positron emission tomography (PET) computed tomography (CT) with 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) has been established as an effective modality for evaluation of cancer. Interpretations of patterns of physiologic 18F-FDG uptake by the heart is particularly difficult given the wide normal variations of 18F-FDG metabolic activity observed. Atypical patterns of focal or diffuse physiologic cardiac 18F-FDG uptake and post-therapeutic effects after radiation therapy, systemic diseases, or cardiomyopathy may also be confused with malignant disease on 18F-FDG PET/CT. In this article, we review the variations of normal cardiac 18F-FDG uptake observed in oncology patients and the appearances of other patterns of pathologic metabolic activity, related or not related to the malignancy being investigated, that may lead to false-negative and false-positive results.
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2.
Transcutaneous electrical nerve stimulation attenuates cardiac sympathetic drive in heart failure: a 123MIBG myocardial scintigraphy randomized controlled trial.
Campos, MO, Nóbrega, ACL, Miranda, SM, Ribeiro, ML, Guerra, TRB, Braghirolli, AMS, Mesquita, CT, Fernandes, IA
American journal of physiology. Heart and circulatory physiology. 2019;(2):H226-H233
Abstract
Cardiac sympathetic overdrive provides inotropic support to the failing heart. However, as myocardial insult evolves, this compensatory response impairs contractile function and constitutes an independent mortality predictor and a primary target in the treatment of heart failure (HF). In this prospective, randomized, double-blind, controlled crossover trial, we proposed cervicothoracic transcutaneous electrical nerve stimulation (CTENS) as a nonpharmacological therapy on cardiac sympathetic activity in patients with HF. Seventeen patients with HF were randomly assigned to an in-home CTENS (30 min twice daily, 80-Hz frequency, and 150-μs pulse duration) or a control intervention (Sham) for 14 consecutive days. Following a 60-day washout phase, patients were crossed over to the opposite intervention. The heart-to-mediastinum ratio (HMR) and washout rate (WR) (indexes of sympathetic innervation density and activity from planar 123iodo-metaiodobenzylguanidine myocardial scintigraphy images, respectively), as well as blood pressure (BP) and heart rate (HR), were quantified before and after each intervention. HMR, BP, and HR did not change throughout the study. Nonetheless, CTENS reduced WR (CTENS -4 ± 10 vs. Sham +5 ± 15%, P = 0.03) when compared with Sham. When allocated in two independent groups, preserved (PCSI, HMR > 1.6, n = 10) and impaired cardiac sympathetic innervation (ICSI, HRM ≤1.6, n = 7), PCSI patients showed an important attenuation of WR (-11 ± 9 vs. Sham +8 ± 19%, P = 0.007) after CTENS. Nonetheless, neither Sham nor CTENS evoked changes in WR of the ICSI patients (P > 0.05). These findings indicate that CTENS attenuates the cardiac sympathetic overdrive in patients with HF and a preserved innervation constitutes an essential factor for this beneficial neuromodulatory impact. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT03354689. NEW & NOTEWORTHY We found that short-term cervicothoracic transcutaneous electrical nerve stimulation (CTENS) attenuates cardiac sympathetic overdrive in patients with heart failure and a preserved autonomic innervation may constitute an essential factor to maximize this beneficial neuromodulatory effect. CTENS then emerges as an alternative noninvasive and nonpharmacological strategy to attenuate exaggerated cardiac sympathetic drive in patients with heart failure.
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3.
The Impact of Emerging Bioconjugation Chemistries on Radiopharmaceuticals.
Fay, R, Holland, JP
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(5):587-591
Abstract
The use of radiolabeled antibodies, immunoglobulin fragments, and other proteins are an increasingly important sector of research for diagnostic imaging and targeted radiotherapy in nuclear medicine. As with all radiopharmaceuticals, efficient radiochemistry is a prerequisite to clinical translation. For proteins, variations in the primary amino acid sequence, the secondary structures, and tertiary folds, as well as differences in the size, charge, polarity, lipophilicity, and the presence of posttranslational modifications, add complexity to the system. The choice of radionuclide or chelate, and its impact on the thermodynamic, kinetic, and metabolic stability of a radiotracer, has attracted much attention but the chemistry by which the radionuclide is conjugated to the protein scaffold is of equal importance. Recently, a wealth of creative advances in protein ligation methods based on chemical, photochemical, and enzyme-mediated processes has emerged. As radiochemists explore alternative bioconjugation strategies, this article considers their potential impact on radiotracer design.
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4.
Diagnostic Performance and Prognostic Value of PET/CT with Different Tracers for Brain Tumors: A Systematic Review of Published Meta-Analyses.
Treglia, G, Muoio, B, Trevisi, G, Mattoli, MV, Albano, D, Bertagna, F, Giovanella, L
International journal of molecular sciences. 2019;(19)
Abstract
BACKGROUND Several meta-analyses reporting data on the diagnostic performance or prognostic value of positron emission tomography (PET) with different tracers in detecting brain tumors have been published so far. This review article was written to summarize the evidence-based data in these settings. METHODS We have performed a comprehensive literature search of meta-analyses published in the Cochrane library and PubMed/Medline databases (from inception through July 2019) about the diagnostic performance or prognostic value of PET with different tracers in patients with brain tumors. RESULTS We have summarized the results of 24 retrieved meta-analyses on the use of PET or PET/computed tomography (CT) with different tracers in brain tumors. The tracers included were: fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 methionine (11C-methionine), fluorine-18 fluoroethyltyrosine (18F-FET), fluorine-18 dihydroxyphenylalanine (18F-FDOPA), fluorine-18 fluorothymidine (18F-FLT), and carbon-11 choline (11C-choline). Evidence-based data demonstrated good diagnostic performance of PET with different tracers in detecting brain tumors, in particular, radiolabelled amino acid tracers showed the highest diagnostic performance values. All the PET tracers evaluated had significant prognostic value in patients with glioma. CONCLUSIONS Evidence-based data showed a good diagnostic performance for some PET tracers in specific indications and significant prognostic value in brain tumors.
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5.
A phase I clinical trial for [131I]meta-iodobenzylguanidine therapy in patients with refractory pheochromocytoma and paraganglioma.
Wakabayashi, H, Inaki, A, Yoshimura, K, Murayama, T, Imai, Y, Higuchi, T, Jinguji, M, Shiga, T, Kinuya, S
Scientific reports. 2019;(1):7625
Abstract
Refractory pheochromocytoma and paraganglioma (PPGL) have a poor prognosis and the treatment strategy remains to be established. This multi-institutional phase I study was performed to determine the safety, dose-limiting toxicity (DLT), and efficacy of [131I]-meta-iodobenzylguanidine (131I-mIBG) therapy for refractory PPGLs. Twenty patients with refractory PPGL were enrolled in this study. We administered fixed doses of 131I-mIBG to all patients, delivering a second and third course of 131I-mIBG to eight and three patients, respectively. During the 20 weeks after 131I-mIBG injection, the authors surveyed the adverse events in accordance with the Common Terminology Criteria for Adverse Events. All patients experienced adverse events and adverse reactions, but none experienced a grade 4 adverse event. Twelve weeks after 131I-mIBG injection, examinations for the evaluation of therapeutic effects was performed in accordance with the Response Evaluation Criteria in Solid Tumours (RECIST). The best overall response rates (based on RECIST categories) were 10% (complete response), 65% (stable disease), 15% (progressive disease), and 10% (not all evaluated). The efficacy and safety of 131I-mIBG therapy was shown in patients with refractory PPGL, and DLT was observed in neither single nor repeated 131I-mIBG therapy, indicating a tolerability for 131I-mIBG therapy.
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6.
Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.
Dhir, V, Yan, AT, Nisenbaum, R, Sloninko, J, Connelly, KA, Barfett, J, Haq, R, Kirpalani, A, Chan, KKW, Petrella, TM, et al
The international journal of cardiovascular imaging. 2019;(11):2085-2093
Abstract
Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.
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7.
Spatial distributions of cholinergic impairment and neuronal hypometabolism differ in MCI due to AD.
Richter, N, Nellessen, N, Dronse, J, Dillen, K, Jacobs, HIL, Langen, KJ, Dietlein, M, Kracht, L, Neumaier, B, Fink, GR, et al
NeuroImage. Clinical. 2019;:101978
Abstract
Elucidating the relationship between neuronal metabolism and the integrity of the cholinergic system is prerequisite for a profound understanding of cholinergic dysfunction in Alzheimer's disease. The cholinergic system can be investigated specifically using positron emission tomography (PET) with [11C]N-methyl-4-piperidyl-acetate (MP4A), while neuronal metabolism is often assessed with 2-deoxy-2-[18F]fluoro-d-glucose-(FDG) PET. We hypothesised a close correlation between MP4A-perfusion and FDG-uptake, permitting inferences about metabolism from MP4A-perfusion, and investigated the patterns of neuronal hypometabolism and cholinergic impairment in non-demented AD patients. MP4A-PET was performed in 18 cognitively normal adults and 19 patients with mild cognitive impairment (MCI) and positive AD biomarkers. In nine patients with additional FDG-PET, the sum images of every combination of consecutive early MP4A-frames were correlated with FDG-scans to determine the optimal time window for assessing MP4A-perfusion. Acetylcholinesterase (AChE) activity was estimated using a 3-compartmental model. Group comparisons of MP4A-perfusion and AChE-activity were performed using the entire sample. The highest correlation between MP4A-perfusion and FDG-uptake across the cerebral cortex was observed 60-450 s after injection (r = 0.867). The patterns of hypometabolism (FDG-PET) and hypoperfusion (MP4A-PET) in MCI covered areas known to be hypometabolic early in AD, while AChE activity was mainly reduced in the lateral temporal cortex and the occipital lobe, sparing posterior midline structures. Data indicate that patterns of cholinergic impairment and neuronal hypometabolism differ significantly at the stage of MCI in AD, implying distinct underlying pathologies, and suggesting potential predictors of the response to cholinergic pharmacotherapy.
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8.
TheraP: a randomized phase 2 trial of 177 Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603).
Hofman, MS, Emmett, L, Violet, J, Y Zhang, A, Lawrence, NJ, Stockler, M, Francis, RJ, Iravani, A, Williams, S, Azad, A, et al
BJU international. 2019;:5-13
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Abstract
OBJECTIVE To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177 Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. PATIENTS AND METHODS The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177 Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68 Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2 ) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177 Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68 Ga-PSMA-11 and Fluorine-18 (18 F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. RESULTS AND CONCLUSIONS 177 Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177 Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.
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Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy.
Locati, LD, Piovesan, A, Durante, C, Bregni, M, Castagna, MG, Zovato, S, Giusti, M, Ibrahim, T, Puxeddu, E, Fedele, G, et al
European journal of cancer (Oxford, England : 1990). 2019;:35-40
Abstract
BACKGROUND Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)-resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy. METHODS The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data. RESULTS From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval [CI], 7.7-12.6) and 23.8 months (95% CI, 19.7-25.0) respectively. CONCLUSION Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
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10.
Impacto de la medicina nuclear en el diagnóstico y tratamiento del cáncer diferenciado de tiroides.
Medina-Ornelas, S, García-Pérez, F, Granados-García, M
Gaceta medica de Mexico. 2018;(4):509-519
Abstract
Los pacientes afectados por el cáncer diferenciado de tiroides habitualmente presentan un curso clínico favorable, ya que la piedra angular del tratamiento es la cirugía; a pesar de esto, algunos pueden desarrollar un ominoso desenlace, debido a las características clinico-patológicas de esta enfermedad. El tratamiento óptimo aún es controvertido, en especial respecto a la extensión de la cirugía, indicaciones de radioyodo y la supresión de la hormona estimulante de la tiroides. La correcta evaluación de los riesgos, antes y después de la cirugía, facilita un selectivo enfoque del tratamiento; destacando la relevancia de revisar el impacto de la medicina nuclear en la correcta evaluación, tratamiento y seguimiento de los pacientes que padecen esta neoplasia. Patients affected by differentiated thyroid cancer usually have a favorable clinical course, since the cornerstone of treatment is surgery; despite this, some patients may develop an ominous outcome, due to the clinical-pathological features of this disease. Optimal treatment remains controversial, especially regarding the extent of surgery, indications for radioiodine and thyroid-stimulating hormone. The correct evaluation of risks before and after surgery facilitates a selective treatment approach; highlighting the importance of reviewing the impact of nuclear medicine on the correct evaluation, treatment and follow-up of patients suffering from this neoplasm.