Radiolabeling strategies and pharmacokinetic studies for metal based nanotheranostics

Abstract

Radiolabeled metal‐based nanoparticles (MNPs) have drawn considerable attention in the fields of nuclear medicine and molecular imaging, drug delivery, and radiation therapy, given the fact that they can be potentially used as diagnostic imaging and/or therapeutic agents, or even as theranostic combinations. Here, we present a systematic review on recent advances in the design and synthesis of MNPs with major focuses on their radiolabeling strategies and the determinants of their in vivo pharmacokinetics, and together how their intended applications would be impacted. For clarification, we categorize all reported radiolabeling strategies for MNPs into indirect and direct approaches. While indirect labeling simply refers to the use of bifunctional chelators or prosthetic groups conjugated to MNPs for post‐synthesis labeling with radionuclides, we found that many practical direct labeling methodologies have been developed to incorporate radionuclides into the MNP core without using extra reagents, including chemisorption, radiochemical doping, hadronic bombardment, encapsulation, and isotope or cation exchange. From the perspective of practical use, a few relevant examples are presented and discussed in terms of their pros and cons. We further reviewed the determinants of in vivo pharmacokinetic parameters of MNPs, including factors influencing their in vivo absorption, distribution, metabolism, and elimination, and discussed the challenges and opportunities in the development of radiolabeled MNPs for in vivo biomedical applications. Taken together, we believe the cumulative advancement summarized in this review would provide a general guidance in the field for design and synthesis of radiolabeled MNPs towards practical realization of their much desired theranostic capabilities. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Core–shell structured gold nanoparticles as carrier for 166Dy/166Ho in vivo generator

“…The improved tumor uptake is likely from the prolonged circulation time of AuNPs comparing with small molecules. However, the toxicity of AuNP itself have to be considered even gold is considered to be biocompatible (Ranjbar Bahadori et al 2021 ).…”

Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

“…While radioactivity at the tumor site compared to the total body activity was considerably low, there was a significant ratio of 99mTclabeled niosomes uptake in the tumor in comparison to the muscle. Accumulation of radioactivity is affected by the route of administration (Bahadori et al, 2021), where nearly perfect tumor retention was observed when radiolabelled nanoparticles are injected intratumorally (Moeendarbari et al, 2016). In this study, niosomes were injected intravenously, hence a lower overall accumulation should be expected.…”

Recent Advances in Brachytherapy Using Radioactive Nanoparticles: An Alternative to Seed-Based Brachytherapy

“…In an archetypical example, radiolabeling nanoparticles with 18 F has been reported by first conjugating cysteamine to mannose triflate (Man-CA) and then 18 F labeling resulting to a cysteamine-linked radiotracer ( 18 F-FDG-CA). The 18 F-FDG-CA is mixed with gold chloride (HAuCl 4 ) to obtain AuNPs ( 18 F-FDG-CA-AuNPs) ( 32 ).…”

“…Radiochemical labeling involves incorporation of the radionuclide as a surrogate during the synthesis of the nanoparticles resulting in intrinsically radioactive nanoparticles often carried out in automated closed lead-shielded unit due to the increased radiation exposure (21,32). This type of radiolabeling is divided into two subcategories: heteroradionuclides, where nanoparticle core cation and the radionuclide are different (e.g., doping AuNPs with 64 Cu or 111 ln), and homo-radionuclides, where a radioisotope of the metal element to form the nanoparticle core is used (e.g., premixture of H 198 AuCl 4 to HAuCl 4 precursor for the production of 198 AuNPS) (10,35,36) Pd]AuPdNPs) with ≈20 nm, and then ethylenediaminetetraacetic acid (EDTA) was used to scavenge free Pd 2+ to avoid unspecific labeling of the nanoparticle surface resulting in radiolabeling efficiencies of 79% to >99%.…”