Polymeric micelles as carriers for a 166Dy/166Ho in vivo generator

Abstract

Cancer is
one of the leading causes of death in the world. Because of this, there are
many novel methods to treat it being currently researched. One of the answers
from the nuclear medicine perspective is Radionuclide Therapy, where alpha or
beta emitters are applied, with the goal to selectively irradiate tumours in
the body. A promising radionuclide researched for Radionuclide Therapy is
Holmium-166, which is a beta emitter with a short half-life of 26.8 hours,
which is useful for the treatment of large metastases. A method to ensure an
effective treatment with Holmium-166 is the use of a Dysprosium-166/Holmium-166
in vivo generator, as the dose delivered to patients per administered dose is
two times higher with the in vivo generator rather than the direct use of
Holmium-166. However, carriers used in Radionuclide Therapy, which usually
involve the formation of a chelator-metal complex are not effective for the in
vivo generator due to the release of auger electrons during the decay process
leading to the destruction of the chelator-metal complex. A promising
non-chelator method designed by Liu et al. at the Applied Radiation and
Isotopes research team at TU Delft involves the radiolabelling of micelles.
This thesis sought to evaluate the use of micelles, radiolabelled with this
mechanism as an effective carrier for the Dysprosium-166/Holmium-166 in vivo
generator. For this, micelles made of Polycaprolactone-block-Polyethylene Oxide
and Polylactic Acidblock-Polyethylene oxide were evaluated based on the
obtained radiolabelling efficiency and their stability when challenged with
diethylenetriaminepentaacetic acid (DTPA). The results in this study show that
the radiolabelling method used to encapsulate Dysprosium relies on the
diffusion of Dysprosium hydroxides into the micelle core, followed by
precipitation as the right concentration is reached inside the micelles. The best
results obtained by this study occur when radiolabelling Polylactic
Acid-block-Polyethylene Oxide (PLA-PEO) micelles, and then adding phosphate
ions at a concentration of 3 × 10−8𝑀, 30 minutes after the addition of
the active Dysprosium. Although more tuning is required on the radiolabelling
mechanism to make micelles the most effective carriers of the 166Dy/166Ho in
vivo generator, promising first steps were made to begin this process