Nanoparticles in Targeted Alpha Therapy

Abstract

Recent advances in the field of nanotechnology application in nuclear medicine offer the promise of better therapeutic options. In recent years, increasing efforts have been made on developing nanoconstructs that can be used as carriers for immobilising alpha (α)-emitters in targeted drug delivery. In this publication, we provide a comprehensive overview of available information on functional nanomaterials for targeted alpha therapy. The first section describes why nanoconstructs are used for the synthesis of α-emitting radiopharmaceuticals. Next, we present the synthesis and summarise the recent studies demonstrating therapeutic applications of α-emitting labelled radiobioconjugates in targeted therapy. Finally, future prospects and the emerging possibility of therapeutic application of radiolabelled nanomaterials are discussed.

Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy

“…A similar reabsorption process of 211 Pb and 211 Bi was also observed in 223 Ra-labeled hydroxyapatites [ 22 ] and nanozeolites [ 23 , 24 ]. Although, according to Holzwart et al [ 53 ], the results obtained in batch measurements, in which the 223 Ra labeled nanoparticles are equilibrated with biological liquids, cannot be transferred to living organism, where blood flow rapidly dislocates the decay products of 223 Ra from the surface of the nanoparticles and reduces the possible readsorption, considering the fast and high internalization properties of [ 223 Ra]BaFe–CEPA–trastuzumab bioconjugate (see Section 3.5 ), it can be expect that after internalization in targeted cells the readsorption process will play an essential role in preventing the escape of 211 Pb and 211 Bi from cancerous cells [ 54 ].…”

Nanoradiopharmaceuticals Based on Alpha Emitters: Recent Developments for Medical Applications

“…Producing alpha emitters implies separating them from natural radionuclides with long half-lives and a combination of alpha emitters that can be generated from either: (a) legacy material, (b) nuclear reactors (neutron irradiation), or (c) accelerators (irradiation with charged particles). After their production, separating the desired radionuclide from the impurities is extremely important [ 5 , 16 ]. Several chemical separation methods, including precipitation, distillation, liquid-liquid extraction, ion exchange, or solid-phase extraction resin separations, can be used to produce radiopharmaceutical-grade alpha emitters for TAT applications [ 5 ].…”

“…211 A is produced in a cyclotron by α particles accelerated to energies of 28–29 MeV bombardment onto a metallic bismuth target via the nuclear reaction 209 Bi(α,2n) 211 At, followed by simple dry distillation and isolation from irradiated bismuth target. This reaction generates energies between 21 and 40 MeV, with a maximum of about 31 MeV for medical applications [ 5 , 16 ]. An alternative method of 211 At production is through a 211 Rn/ 211 At generator.…”

“…Radium (t 1/2 = 11.43 d) decays to stable 207 Pb under emission of four α particles with energies between 5.7 and 7.4 MeV, releasing total energy of ~28 MeV, and is generated from the decay of 227 Ac to 227 Th by the emission of a beta particle followed by alpha emission to produce 223 Ra ( Figure 4 ) [ 16 ]. These radionuclides decay through a cascade of short-lived alpha- and beta-particle emitters to stable lead and bismuth, releasing high total energy of about 28 MeV [ 22 ].…”

“…Table 1 shows the physical properties of several alpha emitters used in TAT [ 5 ]. The most difficult problem with the alpha particle management is associated with the radioisotope daughters release as well as lack of appropriate bifunctional chelating systems affording in vivo stability, a requirement to achieve selective targeting of alpha emitters at tumor sites [ 5 , 16 ]. Currently, targeted therapy using alpha-emitting isotopes presents an opportunity in the development of cancer therapeutic agents for treating various neoplastic diseases.…”