title: (99m)Tc-labelled nanosystem as tumour imaging agent for SPECT and SPECT/CT modalities.
abstract: We report the synthesis, in vitro and in vivo investigation of folate-targeted, biocompatible, biodegradable self-assembled nanoparticles radiolabelled with (99m)Tc, as potential new SPECT or SPECT/CT imaging agent. Nanoparticles with hydrodynamic size in the range of 75-200 nm were prepared by self-assembly of chitosan and folated poly-γ-glutamic acid, and then radiolabelled with (99m)Tc. The nanoparticles target tumour cells overexpressing folate receptors and internalize specifically into them to realize early tumour diagnosis detected by SPECT and SPECT/CT modalities. Rat hepatocellular carcinoma cells were used as model system. Cell specificity and tumour targeting efficacy of these nanosystems were investigated in vitro, and in vivo using SPECT and fusion nanoSPECT/CT imaging. In vitro results showed that the radiolabeled nanosystem was efficiently internalized by tumour cells. Whole-body biodistribution of the new radiolabelled, folate-targeted nanoparticles revealed higher uptake in the tumorous kidney compared to the non-tumorous contralateral side. Uptake by the lungs and thyroids was negligible, which confirmed the stability of the nanoparticles in vivo. In vivo SPECT and SPECT/CT imaging visually reinforced the uptake results and were in accordance with the biodistribution data: the new nanoparticles as a targeted contrast agent improve tumour targeting and are able to detect folate-receptor-overexpressing tumours in animal models with enhanced contrast.
authors.affiliation: National "F.J.C." Research Institute for Radiobiology and Radiohygiene (NRIRR), H-1221 Budapest, Hungary. bandi.polyak@gmail.com
authors.forename: András
authors.initials: A
authors.lastname: Polyák
authors.forename: István
authors.initials: I
authors.lastname: Hajdu
authors.forename: Magdolna
authors.initials: M
authors.lastname: Bodnár
authors.forename: György
authors.initials: G
authors.lastname: Trencsényi
authors.forename: Zita
authors.initials: Z
authors.lastname: Pöstényi
authors.forename: Veronika
authors.initials: V
authors.lastname: Haász
authors.forename: Gergely
authors.initials: G
authors.lastname: Jánoki
authors.forename: Győző A
authors.initials: GA
authors.lastname: Jánoki
authors.forename: Lajos
authors.initials: L
authors.lastname: Balogh
authors.forename: János
authors.initials: J
authors.lastname: Borbély
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D048271:Chitosan / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D058973:Folate Receptors, GPI-Anchored; D019275:Radiopharmaceuticals; D048271:Chitosan; D013670:Sodium Pertechnetate Tc 99m