Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy. Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured. Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure.
The science of 'theranostics' plays a crucial role in personalized medicine, which represents the future of patient management. Over the last decade an increasing research effort has focused on the development of nanoparticle-based molecular-imaging and drug-delivery approaches, emerging as a multidisciplinary field that shows promise in understanding the components, processes, dynamics and therapies of a disease at a molecular level. The potential of nanometer-sized agents for early detection, diagnosis and personalized treatment of diseases is extraordinary. They have found applications in almost all clinically relevant biomedical imaging modality. In this review, a number of these approaches will be presented with a particular emphasis on MRI and optical imaging-based techniques. We have discussed both established molecular-imaging approaches and recently developed innovative strategies, highlighting the seminal studies and a number of successful examples of theranostic nanomedicine, especially in the areas of cardiovascular and cancer therapy.
Background: Although Spectral CT is still in its early clinical development stages, K-edge contrast agents designed to specifically target thrombus could provide rapid stratification of ED patients with unclear CP etiology. Objective: To develop and demonstrate a systemically administered Spectral CT molecular imaging agent to diagnose intravascular thrombus in rabbits. Materials: A nanocolloid (~200nm) comprised of bismuth oleate in oil (20 vol%) encapsulated with phosphatidylcholine and functionalized with an anti-fibrin peptide -PEG2000-phosphatidylethanolamine conjugate was developed (Anti-fibrin BiOL NC). Results: Rabbits with iliac thrombus received anti-fibrin BiOL NC (1.5 ml/kg) via ear vein, which circulated for 2 hrs. The vessels were excised and imaged with a first generation Spectral CT scanner. K-edge contrast enhancement was appreciated in animals receiving anti-fibrin BiOL NC (n=4), but not in those given irrelevant-targeted BiOL NC, fibrin-targeted control nanocolloid or saline. (Figure) O...
Die Einteilung der sehr selten vorkommenden Pseudomyxome, auch als Gallertkarzinome bezeichnet, ist abhängig von der Zellarchitektur sowie dem Wachstums- und Infiltrationsverhalten. Nach Bradlley et al. (WHO) werden Low-grade-Pseudomyxome (G1) von High-grade-Pseudomyxomen (G2-G4) unterschieden. Ronnett et al. teilt sie in disseminierte peritoneale Adenomuzinosen (DPAM) und peritoneal muzinöse Karzinomatosen (PMCA) ein. Mit einer Inzidenz von 1 – 2 Neuerkrankungen pro 1.000.000 Einwohner pro Jahr ohne Geschlechterspezifität entsteht das Pseudomyxoma peritonei am häufigsten auf dem Boden einer muzinösen Neoplasie der Appendix. Nach Ruptur der Mukozele kommt es zur Ausbreitung von Schleimseen in der Abdominalhöhle mit Obstruktion der Organe (jelly belly). Als Metastasierungsorte beobachtet man das rechte Zwerchfell (scalloping liver) sowie das Omentum majus (omental cake). Selten kommt es zu einer hämatogenen oder lymphatischen Metastasierung (Lunge, Knochen, Milz). Diagnostisch werden neben der Sonografie das CT und MRT genutzt. Auch Punktionen des schleimigen Aszites können wegweisend sein. Therapeutisch steht als einzig mögliche Kuration die zytoreduktive Chirurgie (CRS) und hypertherme intraperitoneale Chemoperfusion (HIPEC) zur Verfügung. Dabei werden sowohl das Peritoneum parietale als auch das Peritoneum viszerale der befallenen Organe vollständig reseziert, um anschließend eine intraperitoneale Lavage mit Zytostatika (Oxaliplatin, Doxorubicin, Mitomycin C) durchzuführen, welche mit einer Temperatur von 42 – 43 °C über 30 – 60 Minuten perfundiert werden. Damit kann in Abhängigkeit von der Histologie bei kompletter Tumorresektion eine 5-JÜR von bis zu 85% erreicht werden.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)