Many different iron oxide nanoparticles have been evaluated over the years, for a wide variety of biomedical applications. We here summarize the synthesis, surface functionalization and ...characterization of iron oxide nanoparticles, as well as their (pre-) clinical use in diagnostic, therapeutic and theranostic settings. Diagnostic applications include liver, lymph node, inflammation and vascular imaging, employing mostly magnetic resonance imaging but recently also magnetic particle imaging. Therapeutic applications encompass iron supplementation in anemia and advanced cancer treatments, such as modulation of macrophage polarization, magnetic fluid hyperthermia and magnetic drug targeting. Because of their properties, iron oxide nanoparticles are particularly useful for theranostic purposes. Examples of such setups, in which diagnosis and therapy are intimately combined and in which iron oxide nanoparticles are used, are image-guided drug delivery, image-guided and microbubble-mediated opening of the blood-brain barrier, and theranostic tissue engineering. Together, these directions highlight the versatility and the broad applicability of iron oxide nanoparticles, and indicate the integration in future medical practice of multiple iron oxide nanoparticle-based materials.
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Purpose
To examine the relationship between the extent of disease determined by
68
GaPSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time ...(PSAdt) and Gleason score.
Methods
We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for
68
GaPSMA-HBED-CC PET/CT.
Results
PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 – 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (
p
< 0.001), and extrapelvic lymph node (
p
= 0.037) and bone metastases (
p
= 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (
p
= 0.026), extrapelvic lymph node (
p
= 0.001), bone (
p
< 0.001) and visceral (
p
= 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (
p
= 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (
p
= 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease.
Conclusion
68
GaPSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for
68
GaPSMA-HBED-CC PET/CT.
Conversations about open science have reached the mainstream, yet many open science practices such as data sharing remain uncommon. Our efforts towards openness therefore need to increase in scale ...and aim for a more ambitious target. We need an ecosystem not only where research outputs are openly shared but also in which transparency permeates the research process from the start and lends itself to more rigorous and collaborative research. To support this vision, this Essay provides an overview of a selection of open science initiatives from the past 2 decades, focusing on methods transparency, scholarly communication, team science, and research culture, and speculates about what the future of open science could look like. It then draws on these examples to provide recommendations for how funders, institutions, journals, regulators, and other stakeholders can create an environment that is ripe for improvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically ...assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.
Abstract Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which ...relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. Graphical abstract
Purpose
To investigate whether the numbers of lymph node metastases and coeliac ganglia delineated on
68
GaPSMA-HBED-CC PET/CT scans differ among datasets generated using different reconstruction ...algorithms.
Methods
Data were constructed using the BLOB-OS-TF, BLOB-OS and 3D-RAMLA algorithms. All reconstructions were assessed by two nuclear medicine physicians for the number of pelvic/paraaortal lymph node metastases as well the number of coeliac ganglia. Standardized uptake values (SUV) were also calculated in different regions.
Results
At least one
68
GaPSMA-HBED-CC PET/CT-positive pelvic or paraaortal lymph node metastasis was found in 49 and 35 patients using the BLOB-OS-TF algorithm, in 42 and 33 patients using the BLOB-OS algorithm, and in 41 and 31 patients using the 3D-RAMLA algorithm, respectively, and a positive ganglion was found in 92, 59 and 24 of 100 patients using the three algorithms, respectively. Quantitatively, the SUVmean and SUVmax were significantly higher with the BLOB-OS algorithm than with either the BLOB-OS-TF or the 3D-RAMLA algorithm in all measured regions (
p
< 0.001 for all comparisons). The differences between the SUVs with the BLOB-OS-TF- and 3D-RAMLA algorithms were not significant in the aorta (SUVmean,
p
= 0.93; SUVmax,
p
= 0.97) but were significant in all other regions (
p
< 0.001 in all cases). The SUVmean ganglion/gluteus ratio was significantly higher with the BLOB-OS-TF algorithm than with either the BLOB-OS or the 3D-RAMLA algorithm and was significantly higher with the BLOB-OS than with the 3D-RAMLA algorithm (
p
< 0.001 in all cases).
Conclusion
The results of
68
GaPSMA-HBED-CC PET/CT are affected by the reconstruction algorithm used. The highest number of lesions and physiological structures will be visualized using a modern algorithm employing time-of-flight information.
To assess whether clinical prostate cancer (PCA) related factors and therapy status can predict the degree of tracer uptake on
GaPSMA-HBED-CC PET/CT.
We retrospectively studied 124 patients with ...recurrent an/or metastatic PCA who underwent
GaPSMAHBED-CC PET/CT. The maximum standardized uptake value (SUVmax) was determined in the prostate bed as well as in three size categories (≤ 5 mm, > 5-15 mm, > 15 mm) in pelvic lymph node, extrapelvic lymph node, bone and visceral metastases.
Significant positive correlations between lesion size and SUVmax were found in pelvic lymph node metastases > 5 -≤15 mm (Spearmans rho = 0.502, p = 0.002) as well as in extrapelvic lymph node metastases5 mm (rho = 0.314, p = 0.033) and > 5 ≤-15 mm (rho = 0.614, p < 0.001). SUVmax tended to be higher in the largest diameter category in each anatomic station than in the middle and lower categories. We were unable to find evidence for a relationship between SUVmax and PSA, PSAdt, Gleason score, androgen deprivation therapy, radiation therapy or chemotherapy status.
Measured tracer uptake in
GaPSMA-HBED-CC PET/CT in patients with recurrent/metastasized prostate cancer is significantly influenced by lesion size as a result of partial volume effects in the very small lesions. Clinical indicators of aggressive prostate cancer behaviour such as PSA levels, PSA doubling time or the Gleason score of the primary tumour, as well as the androgen deprivation therapy, radiation therapy or chemotherapy status are not related to measured tracer uptake. ZIEL:: Beantwortung der Frage ob klinisch bestimmbare Faktoren und Therapiestatus bei Prostatakarzinom (PCA) eine Vorhersage zur Traceranreicherung in
GaPSMA-HBED-CC PET/CT liefern können.Material & Methoden: 124 Patienten mit rezidiviertem und/oder metastasiertem PCA die
GaPSMA-HBED-CC PET/CT untergingen, wurden retrospektiv untersucht. Der maximum Standardized Uptake Value (SUVmax) wurde in der Prostataloge gemessen sowie in drei Größen-Kategorien ( 5 mm, > 5-15 mm, > 15 mm) in Metastasen in den pelvinen Lymphknoten-, extrapelvinen Lymphknoten-, Knochen- und viszeralen Metastasen.
Signifikant positive Korrelationen zwischen Läsionsgröße und SUVmax wurden in pelvinen Lymphknotenmetastasen > 5 -≤15 mm (Spearmans rho = 0.502, p = 0.002), extrapelvinen Lymphknotenmetastasen5 mm (rho = 0.314, p = 0.033) und > 5 -≤15 mm (rho = 0.614, p < 0.001) gefunden. Für jede anatomische Lokalisation wurde ein höherer Wert SUVmax innerhalb der größten Kategorie verglichen zu mittleren und kleinsten Kategorie gefunden.
The tumor accumulation of nanomedicines relies on the enhanced permeability and retention (EPR) effect. In the last 5–10 years, it has been increasingly recognized that there is a large inter- and ...intra-individual heterogeneity in EPR-mediated tumor targeting, explaining the heterogeneous outcomes of clinical trials in which nanomedicine formulations have been evaluated. To address this heterogeneity, as in other areas of oncology drug development, we have to move away from a one-size-fits-all tumor targeting approach, towards methods that can be employed to individualize and improve nanomedicine treatments. To this end, efforts have to be invested in better understanding the nature, the complexity and the heterogeneity of the EPR effect, and in establishing systems and strategies to enhance, combine, bypass and image EPR-based tumor targeting. In the present manuscript, we summarize key studies in which these strategies are explored, and we discuss how these approaches can be employed to enhance patient responses.
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PLGA-Based Nanoparticles in Cancer Treatment Rezvantalab, Sima; Drude, Natascha Ingrid; Moraveji, Mostafa Keshavarz ...
Frontiers in pharmacology,
11/2018, Letnik:
9
Journal Article
Recenzirano
Odprti dostop
Nanomedicines can be used for a variety of cancer therapies including tumor-targeted drug delivery, hyperthermia, and photodynamic therapy. Poly (lactic-co-glycolic acid) (PLGA)-based materials are ...frequently used in such setups. This review article gives an overview of the properties of previously reported PLGA nanoparticles (NPs), their behavior in biological systems, and their use for cancer therapy. Strategies are emphasized to target PLGA NPs to the tumor site passively and actively. Furthermore, combination therapies are introduced that enhance the accumulation of NPs and, thereby, their therapeutic efficacy. In this context, the huge number of reports on PLGA NPs used as drug delivery systems in cancer treatment highlight the potential of PLGA NPs as drug carriers for cancer therapeutics and encourage further translational research.
Active targeting can improve the retention of drugs and drug delivery systems in tumors, thereby enhancing their therapeutic efficacy. In this context, vitamin receptors that are overexpressed in ...many cancers are promising targets. In the last decade, attention and research were mainly centered on vitamin B9 (folate) targeting; however, the focus is slowly shifting towards vitamin B2 (riboflavin). Interestingly, while the riboflavin carrier protein was discovered in the 1960s, the three riboflavin transporters (RFVT 1-3) were only identified recently. It has been shown that riboflavin transporters and the riboflavin carrier protein are overexpressed in many tumor types, tumor stem cells, and the tumor neovasculature. Furthermore, a clinical study has demonstrated that tumor cells exhibit increased riboflavin metabolism as compared to normal cells. Moreover, riboflavin and its derivatives have been conjugated to ultrasmall iron oxide nanoparticles, polyethylene glycol polymers, dendrimers, and liposomes. These conjugates have shown a high affinity towards tumors in preclinical studies. This review article summarizes knowledge on RFVT expression in healthy and pathological tissues, discusses riboflavin internalization pathways, and provides an overview of RF-targeted diagnostics and therapeutics.
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