Bestemmelse af topografiske strålingsdosisprofiler ved hjælp af gel nanosensorer

Den rutinemæssige måling af strålingsdoser kan være klinisk udfordrende på grund af begrænsninger med konventionelle dosimetre, der bruges til at måle dosisoptagelsen af ​​ekstern ioniserende stråling. I en ny undersøgelse, Karthik Pushpavanam og et tværfagligt team af forskere i afdelingerne for Kemiteknik, Molekylær Videnskab, Banner MD Anderson Cancer Center og Arizona Veterinary Oncology i USA har beskrevet en ny gel-baseret nanosensor. Teknologien tillader kolorimetrisk påvisning og kvantificering af topografiske stråledosisprofiler under strålebehandling.

Ved udsættelse for ioniserende stråling, forskerne omdannede guldioner i gelen til guldnanopartikler (AuNP'er) ledsaget af en visuel ændring i gelens farve på grund af plasmoniske egenskaber. De brugte intensiteten af ​​farve dannet i gelen som en kvantitativ reporter til ioniserende stråling og brugte først gel nanosensoren til at detektere komplekse topografiske dosismønstre efter administration til antropomorfe fantommodeller efterfulgt af applikationer med levende hundepatienter, der gennemgår klinisk strålebehandling. Den lette fremstilling, operation, hurtig aflæsning, kolorimetrisk detektion og relativt lave omkostninger ved teknologien indebar translationel potentiale for topografisk dosiskortlægning under kliniske strålebehandlingsapplikationer. Forskningsarbejdet er nu offentliggjort på Videnskabens fremskridt .

Fremskridt inden for stråleterapi har ført til bemærkelsesværdig sofistikeret og avanceret planlægningssoftware til at levere høje konforme stråledoser til patienter for forbedret livskvalitet efter behandling. Under strålebehandling, en høj dosis afgives typisk til en måltumor, mens den strålingsdosis, der leveres til omgivende væv, minimeres. Under palliativ behandling administreres patienter med større fraktionerede doser for at afslutte behandlingen inden for en kort tidsramme. Imidlertid, softwarefejl under sådanne procedurer kan føre til overdosering og efterfølgende morbiditet.

For at minimere utilsigtet overeksponering, forskere søger uafhængigt at verificere dosis af stråling leveret ved eller nær målvævet for avanceret patientsikkerhed. Teknisk set, både molekylære og nanosensorer kan overvinde grænser, der findes i konventionelle systemer, for at danne praktiske alternativer som nemme sensorer. Imidlertid, deres eksisterende grænser bør adresseres og afhjælpes for at udvikle robuste og effektive sensorer, der kvantitativt og kvalitativt bestemmer de topografiske dosisprofiler under klinisk strålebehandling.

Siden guld nanopartikler (AuNP'er) har unikke fysiske og kemiske egenskaber, der giver en fremragende platform til at udvikle sensorer. Pushpavanam et al. konstrueret en kolorimetrisk sensor, hvor ioniserende stråling forårsagede AuNP-dannelse fra farveløse saltprækursorer. Dannelsen af ​​en gel-baseret nanosensor kan tillade nem håndtering og anvendelse under klinisk strålebehandling.

I nærværende arbejde, holdet demonstrerede kolorimetrisk detektion og kvantificering af dosisfordelingsprofiler ved hjælp af en gel nanosensor til topografisk kortlægning af strålingsdoser langs vævsoverflader. Under prækliniske evalueringer, holdet administrerede gel nanosensor-teknologien til levende hundepatienter, der gennemgår strålebehandling. I alt, resultaterne indikerede omfanget af teknologien til klinisk translation hos humane patienter og kapaciteten til at bestemme topografiske doser for at planlægge behandlinger og verificere doser under cancerstrålebehandling.

Under forsøgene, omdannelsen af ​​guldioner til nanopartikler blev ledsaget af en rødbrun farveudvikling i det bestrålede område af gel-nanosensoren. Mens guld eksisterer i en trivalent tilstand generelt (AuCl ₄ ^- ) den kan reduceres til en metastabil +1 valenstilstand (AuBr ₂ ^- ) ved stuetemperatur under anvendelse af ascorbinsyre (C-vitamin). Bestrålingen af ​​geler indeholdende terapeutiske niveauer af stråling stimulerede radiolyse eller spaltningen af ​​vandmolekyler i meget reaktive frie radikaler. De radiolyse-genererede hydratiserede elektroner reducerede igen monovalent guld til at danne guldatomer i dets nulvalente tilstand (Au ⁰ ), der nukleerede og modnede til rødbrune AuNP'er. Intensiteten varierede med strålingsdosis, og holdet brugte rækken af ​​lineære responser til at kalibrere gel nanosensoren. Ud fra dette princip, Pushpavanam et al. bestemte responsen af ​​de fuldt bestrålede geler til at kalibrere absorbans med strålingsdosis.

To determine intensity of the color and dose delivered within gels after irradiation, the researchers used absorbance spectroscopy and observed a decrease in the spectral profile width, with increasing radiation dose for decreased polydispersity (ratio of the percentage of the standard deviation to the average value) of the nanoparticles. The peak absorbance intensity increased with increasing radiation dose to corroborate the observed increase in color intensity.

To understand the gel nanosensor's ability to detect topographical distribution of the radiation dose, the scientists irradiated half of the gel nanosensor with a 4 gray (Gy) dose. The maroon-color only appeared in the irradiated area confirming AuNP formation, but after one hour of exposure, the color bled into the irradiated region showing loss of topographic information in the gel with time. The team observed the phenomenon to arise from reaction-controlled conditions and not based on the gel composition. By incubating the gel with sodium sulfide (Na ₂ S) for 10 minutes, they suppressed the color bleed-over and reasoned that to the ability to quench unreacted gold ions in the nonirradiated region and preserve dose information accurately for dose visualization and dosimetry. The scientists adopted the sensor for wide dose ranges by modulating the time of Na ₂ S addition; to achieve a level of flexibility hitherto unavailable in clinical dose detection systems.

The research team then used the gel nanosensor to visualize diverse topographical radiation patterns, where the intensity of the color increased with increasing dose while preserving topographical integrity. As proof of concept, they showed the gel nanosensor's ability to detect complex radiation patterns with a model dose patterned to form "ASU" (after Arizona State University). Then using transmission electron microscopy (TEM), the scientists characterized the generated gold nanoparticles as a function of dose to observe reduced average nanoparticle diameter and polydispersity at higher doses of radiation. They followed this with energy dispersive X-ray spectroscopy (EDS) to detect higher yields of AuNPs in the irradiated regions of the gel nanosensor as expected.

To investigate translational potential of the gel nanosensor and predict topographical profiles of radiation, Pushpavanam et al. first used a head and neck phantom model. They delivered an irregular crescent-shaped radiation dose near the eye to mimic clinically challenging administration modes of radiotherapy close to critical structures such as the eye during skin cancer treatment. The dose profile delivered using the treatment planning system was in excellent agreement with the predictions of the gel nanosensor. Indicating its capability to detect and predict complex radiation patterns similar to those used in clinical human radiotherapy.

During preclinical studies, the research team used two canine models undergoing radiotherapy to investigate the efficiency of gel nanosensors as independent, nanoscale radiation dosimeters for the first time and compared the efficiency with conventional clinical radiochromic films. On completion of the treatment, Pushpavanam et al. observed maroon color formation in one-half of the gel, whereas the non-irradiated region remained colorless. They showed predictions of the gel nanosensor in the irradiated region to agree excellently with the treatment planning system and the radiochromic film. The gel nanosensor also predicted for the region external to the irradiation to receive minimal radiation and their topographical dose profiles as well. The performance was comparable to clinical radiochromic films but with faster than conventional wait times (typically> 24 hours) to obtain the results. The scientists demonstrated the simplicity of fabrication, operation, readout time and cost effectiveness ($ 0.50 per gel material only) of the frugal invention. They maintained the response of the gel nanosensor for at least seven days to indicate long-term retrieval of dosing data unlike with fluorescence-based dosimeters with readouts that lasts mere minutes.

På denne måde Karthik Pushpavanam and colleagues developed the first colorimetric gel nanosensor as a nanoscale dosimeter to detect and distinguish regions exposed to irradiation. They optimized the platform with a chemical quenching agent (Na ₂ S) to accurately reveal topographical dose distribution during clinical radiotherapy. The scientists can control the pore size distribution of the gel substrate to enhance efficacy of the nanosensor. They tested the efficiency of the gel nanosensor to predict complex topographical dose profiles in anthromorphic head and neck phantoms and in live canine patients undergoing radiotherapy. The highly disruptive and translational potential of the gel nanosensor technology will lead to improved patient safety and outcomes in clinical radiotherapy.

© 2019 Science X Network