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Cancers May 2024We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy...
Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.
We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. : All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. : Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.
PubMed: 38893216
DOI: 10.3390/cancers16112097 -
Cancers May 2024Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs... (Review)
Review
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.
PubMed: 38893111
DOI: 10.3390/cancers16111990 -
Cancers May 2024The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu...
The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.
PubMed: 38893095
DOI: 10.3390/cancers16111974 -
Journal of Clinical Medicine May 2024: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented....
: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [F]FDG-PET monitoring of tumor response in patients. : To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. : Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. : These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.
PubMed: 38892979
DOI: 10.3390/jcm13113269 -
International Journal of Molecular... May 2024Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the... (Review)
Review
Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues.
Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the "theranostic pair" concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.
Topics: Scandium; Humans; Radioisotopes; Chelating Agents; Radiopharmaceuticals; Heterocyclic Compounds, 1-Ring; Nuclear Medicine; Animals; Positron-Emission Tomography; Neoplasms; Tomography, Emission-Computed, Single-Photon
PubMed: 38892142
DOI: 10.3390/ijms25115954 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
International Journal of Molecular... May 2024The diverse effects of serotonin on cognition may emerge from the modulation of large-scale brain networks that support distinct cognitive processes. Yet, the specific...
The diverse effects of serotonin on cognition may emerge from the modulation of large-scale brain networks that support distinct cognitive processes. Yet, the specific effect of serotoninergic modulation on the properties of these networks remains elusive. Here, we used a simultaneous PET-fMRI scanner combined with graph theory analyses to investigate the modulation of network properties by the Serotonin Transporter (SERT) availability measured in the dorsal raphe nucleus (DRN). We defined global efficiency as the average mean of efficiencies over all pairs of distinct nodes of specific brain networks, and determined whether SERT levels correlated with the global efficiency of each network. SERT availability in the DRN correlated negatively with the global efficiency of the executive control brain network, which is engaged in cognitive control and directed attention. No relationship was observed between SERT availability and the global efficiency of the default mode or the salience brain networks. These findings indicate a specific role of serotoninergic modulation in the executive control brain network via a change in its global efficiency.
Topics: Serotonin Plasma Membrane Transport Proteins; Humans; Male; Executive Function; Brain; Magnetic Resonance Imaging; Adult; Nerve Net; Female; Positron-Emission Tomography; Serotonin; Young Adult; Dorsal Raphe Nucleus; Brain Mapping
PubMed: 38891901
DOI: 10.3390/ijms25115713 -
International Journal of Molecular... May 2024The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance... (Comparative Study)
Comparative Study
Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.
The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; = 55), late-onset AD (LOAD; = 96), TCP ( = 44), and cognitively unimpaired controls (CTL; = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, = 0.03) and Aβ42/Aβ40 (rho = -0.36, = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.
Topics: Humans; Alzheimer Disease; tau Proteins; Biomarkers; Male; Female; Positron-Emission Tomography; Aged; Amyloid beta-Peptides; Middle Aged; Cognition; Hippocampus; Neurofilament Proteins; Aged, 80 and over; Amnesia; ROC Curve; Clinical Relevance
PubMed: 38891795
DOI: 10.3390/ijms25115607 -
The Kaohsiung Journal of Medical... Jun 2024Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults,... (Review)
Review
Alzheimer disease (AD) and Alzheimer Disease and Related Dementias (AD/ADRD) are growing public health challenges globally affecting millions of older adults, necessitating concerted efforts to advance our understanding and management of these conditions. AD is a progressive neurodegenerative disorder characterized pathologically by amyloid plaques and tau neurofibrillary tangles that are the primary cause of dementia in older individuals. Early and accurate diagnosis of AD dementia is crucial for effective intervention and treatment but has proven challenging to accomplish. Although testing for AD brain pathology with cerebrospinal fluid (CSF) or positron emission tomography (PET) has been available for over 2 decades, most patients never underwent this testing because of inaccessibility, high out-of-pocket costs, perceived risks, and the lack of AD-specific treatments. However, in recent years, rapid progress has been made in developing blood biomarkers for AD/ADRD. Consequently, blood biomarkers have emerged as promising tools for non-invasive and cost-effective diagnosis, prognosis, and monitoring of AD progression. This review presents the evolving landscape of blood biomarkers in AD/ADRD and explores their potential applications in clinical practice for early detection, prognosis, and therapeutic interventions. It covers recent advances in blood biomarkers, including amyloid beta (Aβ) peptides, tau protein, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). It also discusses their diagnostic and prognostic utility while addressing associated challenges and limitations. Future research directions in this rapidly evolving field are also proposed.
PubMed: 38888066
DOI: 10.1002/kjm2.12870 -
European Heart Journal. Case Reports Apr 2024Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed...
BACKGROUND
Desmoplakin cardiomyopathy has been recently classified as a non-dilated left ventricular cardiomyopathy, which is characterized by inflammatory-like episodes followed by left ventricular fibrosis/dysfunction and ventricular arrhythmias. Specific management is unclear.
CASE SUMMARY
We report a detailed case of a 46-year-old Caucasian woman presenting with repeated sudden cardiac arrests who was diagnosed with a new variant in the desmoplakin gene. Because the initial 18F-fluorodeoxyglucose positron emission tomography scan showed significant hypermetabolism, she was treated with immunosuppressors, with only minimal improvement on imaging.
DISCUSSION
Desmoplakin cardiomyopathy should be considered in the differential diagnosis of inflammatory cardiomyopathies. Little is known about the use of immunosuppressive treatments, but it could be reasonable for some selected patients.
PubMed: 38887779
DOI: 10.1093/ehjcr/ytae160