Seite - 53 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Cooperet al. Nanoparticles for radiation therapy detectionpurposes (Moses andDerenzo, 1989, 1990;Wojtowicz etal.,1992,1994;Lempickietal.,1993;Mosesetal.,1994;Rodnyi etal.,1995).Thoughthescintillationwasfoundtobesignificantly faster thancommonlyusedscintillatorsat the time(BGO,CsI:Tl, NaI:Tl)onaper-photonbasis, theoverall lightoutputwas found tobeunexpectedlyweak,withvariable luminescencethatwassig- nificantlydependentonthequalityofthecrystalandthepresence of defects. This variability precluded their use as reliable detec- tors for themost part, at least compared to other options being developedconcurrently, suchasPbWO4. The general process of activator-based scintillation occurs in threesteps:first,conversionofabsorbedionizingradiationenergy intoelectronic-latticeexcitations(electron-holepairsand/orexci- tons), followedbytransferoftheexcitationenergytotheemitting centersandthenluminescence.Theoverall scintillationefficiency isgivenbytheproductof the individualefficiencies: η=βSQ, 0≤η,β,S,Q≤1 where β, the efficiency of the conversion process, encompasses the fractionof absorbed energy lost to optical phonons, S is the efficiencyofthetransferprocess,andQ is theluminescencequan- tum yield of the emitting center. The overall light output L (in photons/MeV) isgivenby: L=ne−hη= 10 6 2.3Eg βSQ wherene−h is thenumberof e-hpairsor excitons that are gener- atedperMeVofabsorbedradiation,discounting losses tooptical phonons, and Egis the band gap of the host (in eV). The fac- tor of 2.3 is related to the derived minimum incident photon energy required to generate a single e-h pair (Robbins, 1980), ξmin=2.3Eg, andsone−h =E/2.3EgwhereE is theenergyofthe incidentphoton, in thiscase1MeV=106 eV. Low phonon energy hosts such as LaF3 tend toward higher values of β, while the transfer process S is relatively inefficient comparedtopentaphosphateororthophosphatehosts(Lempicki etal., 1993).Theβ andSmechanismsofCexLa1−xF3weredeter- mined to consist of three distinct processes that have different relativecontributionsdependingonthevalueofx: (i)directexci- tationofCe3+byX-raysorsecondaryelectrons, (ii) ionizationof Ce3+ followedbyelectroncaptureand formationofboundexci- tons, or (iii) energy transfer to Ce3+ from lattice excitations of thebulkmatrix.At lower concentrationsofCe3+, up tox∼0.5, mechanism (iii) dominates the scintillation response. At higher doping levels, mechanism (i) is predominant, accounting for a large fraction of the light output in CeF3. It has recently been demonstrated that co-doping single crystals of YPO4:Ce3+with Pr3+, which act as electron traps, can improve scintillation effi- ciencybyminimizingtheinfluenceofdefectsaswellasmitigating the effects of damage caused by prolonged irradiation (Moretti etal., 2014). Nanoscintillators Anumber of reports have investigated the scintillation response of CexLa1−xF3 nanocomposites, where small NPs (∼10nm in diameter) are cast into oleic acid or polymer matrices with consistencies ranging from liquid to waxy. In initial studies, nanocomposites exhibited photopeaks for 137Cs, 241Am, and 57Co irradiation (McKigney et al., 2007a,b). Most recently, a modest scintillation response (compared to aBC-400polyvinyl- toluenedetector)hasbeenshownfor25%NP-loadedcomposites exposed to several sources: 22Na (3.22μCi), 60Co (3.78μCi), 137Cs (31.9μCi), 241Am (9.09μCi), and 252Cf (5.03μCi) (Guss et al., 2013). For radiation detection purposes, fast lifetimes are typically preferred, whereas for bioconjugates, short lifetimes may preclude efficient energy transfer if it is outcompeted by luminescenceorquenchingprocesses. While the scintillation of cerium in simple fluoride or phos- phate hosts is well studied, it is just one of a number of pos- sible scintillation mechanisms. In the late 2000s, a number of reportswere released discussing the possibilities and limitations for nanoscintillators in a broad sense, including the demon- stration of a few crucial nanoscale phenomena (Klassen et al., 2008, 2009;Dujardinet al., 2010;Kortov, 2010). Several research groups are now engaged in the development of a wider variety of nanoscintillators, either through adaptation of known scin- tillating materials to the nanoscale, or through the creation of novel compositions. Many of these are based on luminescent “activator”dopants, including lanthanides (Ce3+,Pr3+,Tb3+, or Eu2/3+). RL spectra have been published for a number of fluo- ride nanoscintillators, including powdered LaF3:Eu (∼4.4nm), BaF2:Ce (∼10nm), and CaF2:Eu (∼18nm) NPs under excita- tion by a 40kV Bullet X-ray tube and CaF2:Eu3+ excited by a 1μCi 241Am source (Eα =5.5MeV, Eγ = 60keV) (Jacobsohn etal.,2011).Theauthorssuggestthatinsuchdopedioniccrystals, where thediffusion lengthof e-hpairsmaybeup to100nm, it is conceivable that scintillation yieldsmay be limited by the phys- ical dimensions of theNPs or by the total number of activators. The same grouphas also compared the effects of undopedLaF3 shell thickness on thephotoluminescence vs. RLof LaF3:EuNPs (Jacobsohn et al., 2010). Theundoped shells act as a passivating barrier that is transparent to both optical excitation and emis- sion, andPLefficiencywas found to increase in a roughly linear fashion as a functionof overallNP size as additional shellswere added.With X-ray excitation, the shells were found to increase RLefficiencyup to a shell volumeof roughly twice the core vol- ume,beyondwhichthe lightyielddecreasedwithadditional shell thickness. Thiswas attributed to the increasedundoped volume decreasing theprobability of radiative recombinationwithin the Eu-doped core volume, and suggesting that the diffusion length ofcarriers inLaF3 toberelatively short. Indeed, the luminescence of core-only activator-based nanoscintillators has been found to be size-dependent in some cases. One study demonstrated a considerable broadening of Eu3+ emission lines in progressively smallerGd2O3NPhosts as compared to bulk crystals, attributed to increasing crystal field fluctuations in thesmallerNPs(Dujardinetal., 2010).Anumber of physicalmechanismspotentially influencingnanoscintillators are described in the report, including structural effects, surface effects, quantum confinement, and dielectric confinement. Also shown was a significant difference in the RL spectra of bulk vs. nanoscale CeF3 samples. Intriguing scintillation behavior Frontiers inChemistry | ChemicalEngineering October2014 |Volume2 |Article86 | 53