RESUMEN
Dual emissions at ~700 and 800 nm have been achieved from a single NIR-AZA fluorophore 1 by establishing parameters in which it can exist in either its isolated molecular or aggregated states. Dual near infrared (NIR) fluorescence color lymph node (LN) mapping with 1 was achieved in a large-animal porcine model, with injection site, channels and nodes all detectable at both 700 and 800 nm using a preclinical open camera system. The fluorophore was also compatible with imaging using two clinical instruments for fluorescence guided surgery. Methods: An NIR-AZA fluorophore with hydrophilic and phobic features was synthesised in a straightforward manner and its aggregation properties characterised spectroscopically and by TEM imaging. Toxicity was assessed in a rodent model and dual color fluorescence imaging evaluated by lymph node mapping in a large animal porcine models and in ex-vivo human tissue specimen. Results: Dual color fluorescence imaging has been achieved in the highly complex biomedical scenario of lymph node mapping. Emissions at 700 and 800 nm can be achieved from a single fluorophore by establishing molecular and aggregate forms. Fluorophore was compatible with clinical systems for fluorescence guided surgery and no toxicity was observed in high dosage testing. Conclusion: A new, biomedical compatible form of NIR-dual emission wavelength imaging has been established using a readily accessible fluorophore with significant scope for clinical translation.
Asunto(s)
Endoscopía/métodos , Colorantes Fluorescentes/administración & dosificación , Ganglios Linfáticos/diagnóstico por imagen , Imagen Óptica/métodos , Animales , Endoscopía/instrumentación , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/toxicidad , Células HeLa , Humanos , Cuidados Intraoperatorios/instrumentación , Cuidados Intraoperatorios/métodos , Microscopía Intravital/métodos , Metástasis Linfática/diagnóstico , Masculino , Modelos Animales , Neoplasias/patología , Neoplasias/cirugía , Imagen Óptica/instrumentación , Porfobilinógeno/administración & dosificación , Porfobilinógeno/análogos & derivados , Porfobilinógeno/química , Porfobilinógeno/toxicidad , Ratas , Espectrofotometría Infrarroja/instrumentación , Espectrofotometría Infrarroja/métodos , Sus scrofa , Pruebas de Toxicidad Subaguda/métodosRESUMEN
At least 4 possible mechanisms may be postulated to explain the neural manifestations of acute porphyria in the hereditary hepatic porphyrias. These are (i) excessive amounts of porphyrins or porphyrin precursors produced in the liver during acute attacks are transported to the central and peripheral nervous system, where they exert neurotoxic effects; (ii) unidentified metabolites of the aforementioned compounds may be responsible; (iii) in patients with these diseases there may be a metabolic defect in neural haem biosynthesis which is aggravated by precipitating factors, thereby leading to acute neural manifestations; and (iv) the hepatic and nervous system lesions may be metabolically quite unrelated. Each of these possibilities is considered, and evidence is adduced that a genetic defect in haem biosynthesis in the nervous system is the most plausible hypothesis.