Androgen receptor-targeting agents, particularly enzalutamide, show promise in enhancing prostate cancer diagnostic and therapeutic strategies by modulating prostate-specific membrane antigen (PSMA). Methods: A retrospective clinical cohort study investigated 9 men with metastatic castration-resistant prostate cancer on enzalutamide. PSMA PET/CT scans were obtained before and after enzalutamide initiation to assess PSMA expression changes. Lesions and organs at risk were evaluated visually and semiquantitatively. The flare phenomenon was characterized by a significant increase (≥20%) in the SUVmax of existing lesions or the appearance of new PSMA-positive lesions. Results: Exposure to enzalutamide led to a significant PSMA expression increase in 56% of assessed lesions (n = 42), with new lesions detected in 1 patient (11%). PSMA expression in organs at risk remained largely unaffected, indicating a tumor-specific response. Conclusion: Enzalutamide induces PSMA upregulation in metastatic castration-resistant prostate cancer, potentially enhancing diagnostic and therapeutic strategies. Further exploration of the flare phenomenon's clinical implications is warranted.
- MeSH
- antigeny povrchové * metabolismus MeSH
- benzamidy * MeSH
- fenylthiohydantoin * terapeutické užití analogy a deriváty MeSH
- glutamátkarboxypeptidasa II * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie diagnostické zobrazování metabolismus MeSH
- nitrily * terapeutické užití MeSH
- PET/CT * MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- upregulace * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced magnetic resonance imaging. 18F-fluoroethyl-tyrosine (18F-FET) is a radiopharmaceutical that accumulates in glioma cells due to an increased expression of L-amino acid transporters and, contrary to gadolinium, does not depend on blood-brain barrier disruption to reach tumoral cells. It has demonstrated a high diagnostic value in the differentiation of tumoral viability and pseudoprogression or any other therapy-related changes, especially when combining traditional visual analysis with modern radiomics. In this review, we aim to cover the potential role of 18F-FET positron emission tomography in everyday clinical practice when applied to the follow-up of patients after the first therapeutical intervention, early response evaluation, and the differential diagnosis between therapy-related changes and progression.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Prostate cancer is dependent on the action of steroid hormones on the receptors. Endocrine therapy inhibits hormone production or blocks the receptors, thus providing clinical benefit to many, but not all, oncological patients. It is difficult to predict which patient will benefit from endocrine therapy and which will not. Positron Emission Tomography (PET) imaging of androgen receptors (AR) may provide functional information on the likelihood of endocrine therapy response in individual patients. In this article, we review the utility of [18F]FDHT-PET imaging in prostate, breast, and other hormone-dependent cancers expressing AR. The methodologies, development, and new possibilities are discussed as well.
AIMS: Drug tolerability refers to the degree to which drugs' overt adverse effects can be tolerated by patients. The tolerability profile is of comparative importance to its efficacy and safety, as it largely determines adherence to treatment and ultimately treatment success or failure. However, the term is frequently used imprecisely, and it is unclear if tolerability is limited to subjective patient-reported symptoms or also covers certain objective signs and findings. The aim of this systematic review was to assess how clinical studies define, evaluate and present drug tolerability. METHODS: The study consisted of a systematic review of clinical studies in PubMed® reporting the term "tolerability". RESULTS: Eighty clinical studies were screened and 56 studies reporting drug tolerability were retained. None of the retained studies defined events encompassed by the term tolerability by making a distinction between safety and tolerability. Twenty-five studies claimed to evaluate tolerability, but none of them described how to evaluate tolerability from the patient perspective. Most studies (54 out of 56) concluded that the treatment was well tolerated, apparently implying favourable safety. However, none of them actually presented tolerability in terms of a contrast between safety and tolerability. CONCLUSIONS: Tolerability is used frequently, albeit incorrectly, to refer to a drug's favourable safety profile. Focused evaluation of drug tolerability (i.e., the patient perspective of adverse drug reactions) should become routine. Presentation in regulatory documents, such as risk management plan summaries, product information and patient leaflets should be a continuation of the process of patient-centred healthcare.
- MeSH
- lidé MeSH
- nežádoucí účinky léčiv * epidemiologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Prostate-specific membrane antigen (PSMA)-negative neuroendocrine prostate cancer (PCa) is a subtype of PCa likely to be lethal, with limited clinical diagnostic and therapeutic options. High expression of neurotensin receptor subtype 1 (NTR1) is associated with neuroendocrine differentiation of PCa, which makes NTR1 a potential target for neuroendocrine PCa. In this study, the NTR1-targeted tracer 68Ga-DOTA-NT-20.3 was synthesized, and its affinity to androgen-dependent (LNCap) and androgen-independent (PC3) xenografts was determined. Methods:68Ga-DOTA-NT-20.3 was labeled using an automated synthesizer module, and its stability, labeling yield, and radiochemical purity were analyzed by radio-high-performance liquid chromatography. Receptor binding affinity was evaluated in NTR1-positive PC3 cells by a competitive binding assay. The biodistribution of 68Ga-DOTA-NT-20.3 in vivo was evaluated in PC3 and LNCap xenografts by small-animal PET imaging. NTR1 expression was identified by immunohistochemistry and immunofluorescence evaluation. Results:68Ga-DOTA-NT-20.3 was synthesized successfully, with a yield of 88.07% ± 1.26%, radiochemical purity of at least 99%, and favorable stability. The NTR1 affinity (half-maximal inhibitory concentration) for 68Ga-DOTA-NT-20.3 was 7.59 ± 0.41 nM. Small-animal PET/CT of PC3 xenograft animals showed high-contrast images with intense tumor uptake, which revealed specific NTR1 expression. The tumors showed significant radioactivity (4.95 ± 0.67 percentage injected dose per gram of tissue [%ID/g]) at 1 h, which fell to 1.95 ± 0.17 %ID/g (P < 0.01, t = 8.72) after specific blockage by neurotensin. LNCap xenografts had no significant accumulation (0.81 ± 0.06 %ID/g) of 68Ga-DOTA-NT-20.3 at 1 h. In contrast, 68Ga-PSMA-11 was concentrated mainly in LNCap xenografts (8.60 ± 2.11 %ID/g), with no significant uptake in PC3 tumors (0.53 ± 0.05 %ID/g), consistent with the in vitro immunohistochemistry findings. Biodistribution evaluation showed rapid clearance from the blood and main organs (brain, heart, lung, liver, muscle, and bone), with significantly high tumor-to-liver (4.41 ± 0.73) and tumor-to-muscle (12.34 ± 1.32) ratios at 60 min after injection. Conclusion:68Ga-DOTA-NT-20.3 can be efficiently prepared with a high yield and high radiochemical purity. Its favorable biodistribution and prominent NTR1 affinity make 68Ga-DOTA-NT-20.3 a potential radiopharmaceutical for the detection of PSMA-negative PCa and identification of neuroendocrine differentiation.
- MeSH
- androgeny MeSH
- heterocyklické sloučeniny monocyklické MeSH
- izotopy gallia MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty * patologie MeSH
- neurotensin metabolismus MeSH
- PET/CT metody MeSH
- pozitronová emisní tomografie metody MeSH
- radiofarmaka chemie MeSH
- radioizotopy galia * MeSH
- receptory neurotensinu MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Beta amyloid (Aβ) causes synaptic dysfunction leading to neuronal death. It is still controversial if the magnitude of Aβ deposition correlates with the degree of cognitive impairment. Diagnostic imaging may lead to a better understanding the role of Aβ in development of cognitive deficits. The aim of the present study was to investigate if Aβ deposition in the corresponding brain region of early stage Alzheimer ́s disease (AD) patients, directly correlates to neuronal dysfunction and cognitive impairment indicated by reduced glucose metabolism. PATIENTS AND METHODS: In 30 patients with a clinical phenotype of AD and amyloid positive brain imaging, 2-[18F] fluoro-2-deoxy-d-glucose (FDG) PET/CT was performed. We extracted the average [18F] flutemetamol (Vizamyl) uptake for each of the 16 regions of interest in both hemispheres and computed the standardized uptake value ratio (SUVR) by dividing the Vimazyl intensities by the mean signal of positive and negative control regions. Data were analysed using the R environment for statistical computing and graphics. RESULTS: Any negative correlation between Aβ deposition and glucose metabolism in 32 dementia related and corresponding brain regions in AD patients was not found. None of the correlation coefficient values were statistically significant different from zero based on two-sided p- value. CONCLUSIONS: Regional Aβ deposition did not correlate negatively with local glucose metabolism in early stage AD patients. Our findings support the role of Aβ as a valid biomarker, but does not permit to conclude that Aβ is a direct cause for an aberrant brain glucose metabolism and neuronal dysfunction.
- MeSH
- Alzheimerova nemoc * diagnostické zobrazování metabolismus MeSH
- amyloidní beta-protein metabolismus MeSH
- fluorodeoxyglukosa F18 MeSH
- glukosa metabolismus MeSH
- lidé MeSH
- PET/CT MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Over the last decades, multiple peptide receptors were recognized as potential diagnostic and therapeutic targets in nuclear medicine. 68Ga-NT-20.3 radiopharmaceutical has been developed for diagnosis of neurotensin receptors. High neurotensin receptor expression has been observed in pancreatic ductal adenocarcinoma as well as various malignancies. Until now, 68Ga-labelled NT ligand was successfully applied in in vitro as well as in animal model. Our study is the first in-human study on safety and tolerability of 68Ga-NT-20.3. METHODS: Subjects were intravenously injected with 2.5 MBq of 68Ga-DOTA-NT-20.3 per kilogramme of body weight, and series of PET images were acquired at 5-25 min, 25-45 min, 45-65 min, and 65-85 min after 68Ga-NT-20.3 injection. Vital parameters are as follows: systolic and diastolic blood pressure (mmHg), heart rate (heart beat/min), respiratory rate (number of breaths/min), ECG, and body temperature (°C) were checked before, immediately after, and 3 h after 68Ga-NT-20.3 injection. The organ-absorbed doses were calculated for the self-dose and cross-dose from each organ region using the OLINDA/EXM version 2.1 software. RESULTS AND CONCLUSION: The results from this small trial demonstrate that PET radiopharmaceutical 68Ga-NT-20.3 is safe and well tolerated.
- MeSH
- duktální karcinom slinivky břišní * diagnostické zobrazování MeSH
- lidé MeSH
- nádory slinivky břišní * diagnostické zobrazování MeSH
- radiofarmaka MeSH
- radioizotopy galia MeSH
- receptory neurotensinu MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
Somatostatin analogues are considered to be the first line of treatment in acromegaly. Somatostatin analogues of the first generation mainly target the somatostatin receptor (SSTR) subtype 2 and have been proven efficient in the majority of patients with acromegaly. Pasireotide was the first somatostatin analogue also substantially targeting the SSTR subtype 5. An efficient drug for Cushing's disease tailored to suboptimal-responding patients with acromegaly then became available. We immunohistochemically investigated SSTR subtypes expression in pituitary adenomas from operated acromegaly patients with clinical relapse and a complicated clinical course. Patients received pasireotide in the course of their disease. The predictive value of SSTR subtypes immunhistochemical analysis for the therapeutic response is discussed.
- Publikační typ
- kazuistiky MeSH
Not required for Clinical Vignette.
- MeSH
- adenom * komplikace farmakoterapie MeSH
- akromegalie * MeSH
- lidé MeSH
- nádory hypofýzy * komplikace farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Buňky duktálního adenokarcinomu pankreatu (PDAC) exprimují neurotenzinové receptory. Preklinické testy úspěšně ukázaly, že analogy neurotenzinu značené radionuklidy mají potenciál pro PET zobrazování duktálního adenokarcinomu pankreatu. První in vivo vyšetření pacientů s užitím 68Ga DOTA-NT-20.3 však na rozdíl od preklinických studií nezobrazily nádory PDAC ve všech případech s vysokým kontrastem vůči okolí. Pro praktické užití bude tedy nutno pokračovat v nadějném výzkumu na poli analogů neurotenzinu se snahou modifikovat postupy s cílem dále zvýšit afinitu peptidových radiofarmak k neurotenzinovým receptorům.
Cells of pancreatic ductal adenocarcinoma (PDAC) express neurotensin receptors. Preclinical trials have successfully shown that neurotensin analogues have the potential for PET imaging of PDAC. Based on the published data, NTR-1 is promising target for the development of radioactive analogues for both imaging and therapy in patients with primary and metastatic pancreatic ductal adenocarcinoma. However, the first in vivo studies using 68Ga DOTA-NT-20.3 in patients did not image PDAC tumours in all cases with very high contrast to surrounding tissue. Peptid research in the field of neurotensin analogues continues in an effort to further enhance the affinity of PET peptide radiopharmaceuticals for neurotensin receptors.
