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FORNY20-FORNY2020

KVAL: Alginate-based nanoparticle for targeted delivery of radionuclides (ALDERA)

Awarded: NOK 0.50 mill.

Cancer treatment involves various treatment strategies (chemotherapy, surgery, radiotherapy and eventually targeted radiotherapy). Targeted radiation therapy or radiopharmaceutical therapy (RPT) are drugs (radiopharmaceuticals) that deliver radiation more specifically to tumorous lesions (tumors and metastases) without damaging healthy cells to the same extent. RPT is a safe and effective approach to the treatment of many types of cancer. Challenges with existing radiopharmaceuticals may include limited uptake of radioisotopes in tumours, non-specific conjugation, heterogeneous isotope-to-antibody ratios as well as long residence time in circulation and non-tumorigenic tissue. There is therefore a need for new stable, but biodegradable delivery methods within RPT, with optimal radiation energy that accumulates at/or in the tumor with tolerable systemic toxicity. This may enable a clinically measurable change in the way cancer is diagnosed and treated. Researchers at NTNU have recently developed a new type of alginate-based nanoparticle (aldera) for the targeted delivery of radionuclides, which, unlike conventional alginate-based microgels or microscale precipitates, can be formulated on a nanoscale, enabling systemic delivery (injection into the bloodstream). Aldera can bind several types of multivalent radionuclides and has great potential in diagnostics via positron emission tomography (PET) from positron-emitting radioisotopes, as well as combined PET and targeted therapy (teragnostics). Optimization of Aldera composition and production, related to stability and ion-binding properties, has now been established at NTNU. Binding and stability of Aldera with radioisotope (64Cu2+) is continuously addressed to achieve optimal radioactivity levels per ALDERA particle. Initial experiments with Cu2+ and 64Cu2+ binding have been carried out and studies on the biodynamics of 64Cu-Aldera in cancer models in mice are to be initiated. Further processing, functionalization and pharmacokinetic studies at the PET center St.Olavs hospital are being planned.

Produksjonsmetodikk for en ny generasjon stabile, biokompatible, nedbrytbare alginatbaserte nanopartikler (Aldera) er etablert ved NTNU. Kunnskap om effekt av biopolymerenes blokklengde mhp partiklenes egenskaper (stabilitet og størrelse) er etablert. Videre optimalisering av Cu-binding pågår. Resultatene muligjør videre farmakodynamikk-studier i musemodeller (xenograft). Foreløpige resultater underbygger at Aldera kan bli et nytt radiofarmaka egnet til målrettet behandling av kreft med potensielle fordeler sammenlignet med state-of-the-art, inkludert økt radioisotopbindingseffektivitet, stabilitet, lav toksisitet, fleksibilitet med hensyn til valg av radioisotoper samt mulighter for funksjonalisering av partiklenes overflate.

Funding scheme:

FORNY20-FORNY2020