Biological behaviour of 90Y-labeled micro- and nanoparticles in tumor-bearing mice

Radioisotopes such as 90 Y that emit beta-particles are well known to be suitable for use in tumor therapy. In addition, the delivery of a variety of therapeutics using nanoparticles has become a large field of research in recent years. This study examined the biological behavior of three different micro- and nanoparticle formulations that carry the therapeutic 90 Y radioisotope. The first formulation was 90 Y-labeled citrate-coated superparamagnetic iron-oxide nanoparticles ( 90 Y-CA-SPIONs), the second was mesoporous silica-coated superparamagnetic iron-oxide nanoparticles ( 90 Y-Mag-MSN), and third formulation was 90 Y-labelled albumin microspheres ( 90 Y-AMS). All three formulations are shown to be stable over the relevant period of radioisotope decay. The sizes of particles were 22nm, 386nm, and 38μm for 90 Y-CA-SPIONs, 90 Y-Mag-MSN, and 90 Y-AMS, respectively. The biodistribution studies were done using tumor-bearing BALB/c mice. The results showed that, after the i.v. injection, the biodistribution was dependent on particle sizes. Thus, smaller particles (90 Y-CA-SPIONs and 90 Y-Mag-MSN) were taken up mainly by the liver and spleen (>90%ID), and larger particles (90Y-AMS) were taken up entirely by the lungs. None of the formulations had a tumor uptake of more than 1%ID. After the direct intratumoral injection, all three formulations have shown to be stable, and radioactivity remained only in tumors during the four days of follow-up. This study confirms the delivery of nanoparticles to solid tumors after i.v. injection is a challenge due to the low uptake by tumor tissue. Nevertheless, all three examined materials have shown to be suitable for a direct intratumoral application, and 90 Y-AMS is suitable for radioembolization (SIRT) procedures. Radioizotopi, kao što je 90 Y, koji emituju beta-čestice su pogodni za upotrebu u terapiji tumora. Pored toga, isporuka terapeutika pomoću nanočestica predstavlja poslednjih godina veliko polje istraživanja. U ovoj studiji je ispitivano biološko ponašanje tri različite formulacije mikro- i nanočestica obeleženih terapeutskim radioizotopom 90 Y. Prvu formulaciju su činile 90 Y-obeležene su perparamagnetne nanočestice gvožđe-oksida obložene citratom (90 Y-CA-SPIONs), druga je bila superparamagnetna nanočestica gvožđe-oksida obložena mezoporoznom silikom (90 Y-Mag-MSN), a treća formulacija je bila 90 Y-obeležena albuminska mikrosfera ( 90 Y-AMS). Pokazalo se da su sve tri formulacije stabilne tokom perioda poluraspada radioizotopa. Veličine čestica bile su 22 nm, 386 nm i 38 μm za 90 Y-CA- SPION, 90 Y-Mag-MSN i 90 Y-AMS, respektivno. Studije biodistribucije su urađene korišćenjem BALB/c miševa sa tumorskim ksenograftima. Rezultati su pokazali da, nakon i.v. injekcije, biodistribucija radioobeleženih čestica zavisi od njihove veličine. Prema tome, manje čestice ( 90 Y-CA-SPIONs i 90 Y-Mag-MSN) se uglavnom nakupljaju u jetri i slezini (>90%ID), a veće ( 90 Y-AMS) u plućima. Nakupljanje čestica u tumorima je bilo manje od 1%ID. Posle direktne lokalne intratumoralne injekcije, sve tri vrste radioobeleženih čestica su pokazale visoku stabilnost, tako da se radioaktivnost zadržala isključivo u tumorskom tkivu tokom četiri dana praćenja. Ova studija potvrđuje da je nakupljanje nanočestica u solidnim tumorima nakon i.v. injekcije izazov zbog malog preuzimanja od strane tumorskog tkiva. Ipak, sve tri ispitivane vrste čestica su se pokazale pogodnim za direktnu lokalnu intratumoralnu primenu, a 90 Y- AMS je pogodan i za terapiju radioembolizacijom (SIRT). VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd