Nanoscale Radiotheranostics for Cancer Treatment: From Bench to Bedside.

In recent years, the application of radionuclides-containing nanomaterials in cancer treatment has garnered widespread attention. The diversity of nanomaterials allows researchers to selectively combine them with appropriate radionuclides for biomedical purposes, addressing challenges faced by peptides, small molecules, or antibodies used for radionuclide labeling. However, with advantages come challenges, and nanoradionuclides still encounter significant issues during clinical translation. This review summarized the recent progress of nanosized radionuclides for cancer treatment or diagnosis. The discussion began with representative radionuclides and the methods of incorporating them into nanomaterial structures. Subsequently, new combinations of nanomaterials and radionuclides, along with their applications, were introduced to demonstrate their future trends. The benefits of nanoradionuclides included optimized pharmacokinetic properties, enhanced disease-targeting efficacy, and synergistic application with other treatment techniques. Besides, the basic rule of this section was to summarize how these nanoradionuclides can truly impact the diagnosis and therapy of various cancer types. In the last part, the focus was devoted to the nanoradionuclides currently applicable in clinics and how to address the existing issues and problems based on our knowledge.

Radiolabeling of amide functionalized multi-walled carbon nanotubes for bioaccumulation study in fish bone using whole-body autoradiography.

Commercial and medicinal applications of functionalized carbon nanotubes (f-CNTs) such as amidated f-CNTs are expanding rapidly with a potential risk exposure to living organisms. The effects of amidated f-CNTs on aquatic species have received a limited attention. In this work, an easy wet method to prepare [14C]-label amide multi-walled carbon nanotubes (MWNTs) is reported. Labeled carbon nanotubes were prepared by successive reactions of carboxylation, chloroacylation, and final amidation using [14C]-labeled ethanolamine. The f-CNTs were characterized using elemental analysis, electron dispersive X-ray, transmission electron microscopy, thermogravimetric analysis, and Raman and FTIR spectroscopy. An uptake experiment was carried out with juvenile Arctic char (Salvelinus alpinus) using water dispersed amidated [14C]-f-CNTs to assess their biodistribution in fish tissues using whole body autoradiography. The radioactivity pattern observed in fish head suggests that f-CNTs were accumulated in head bone canals, possibly involving an interaction with mineral or organic phases of bones such as calcium and collagen. This f-CNTs distribution illustrates how important is to consider the surface charges of functionalized carbon nanotubes in ecotoxicological studies.

One-step preparation of [(18)F]FPBM for PET imaging of serotonin transporter (SERT) in the brain.

Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [(18)F]FPBM, 2-(2'-(dimethylamino)methyl)-4'-(3-([(18)F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [(18)F]F(-)/K222 to produce [(18)F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [(18)F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [(18)F]FPBM (radiochemical yield, 24-33%, decay corrected; radiochemical purity >99%). PET imaging studies in normal monkeys (n=4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5mg/kg iv injection at 30min after [(18)F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [(18)F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [(18)F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [(18)F]FPBM for in vivo PET imaging of SERT binding in the brain.

An improved preparation of [18F]FPBM: a potential serotonin transporter (SERT) imaging agent.

INTRODUCTION: In vivo positron emission tomography (PET) imaging of the serotonin transporter (SERT) is a valuable tool in drug development and in monitoring brain diseases with altered serotonergic function. We have developed a two-step labeling reaction for the preparation of the high serotonin affinity ligand [(18)F]FPBM ([(18)F]2-(2'-((dimethylamino)methyl)-4'-(3-fluoropropoxy)phenylthio)benzenamine, 1). METHOD: To improve and automate the radiolabeling of [(18)F]FPBM, 1, an intermediate, [(18)F]3-fluoropropyltosylate, [(18)F]4, was prepared first, and then it was reacted with the phenol precursor (4-(2-aminophenylthio)-3-((dimethylamino)methyl)phenol, 3) to afford [(18)F]FPBM, 1. To optimize the labeling, this O-alkylation reaction was evaluated under different temperatures, using different bases and varying amounts of precursor 3. The desired product was obtained after a solid phase extraction (SPE) purification. RESULTS: This two-step radiolabeling reaction successfully produced the desired [(18)F]FPBM, 1, with an excellent radiochemical purity (>95%, n = 8). Radiochemical yields were between 31% and 39% (decay corrected, total time of labeling: 70 min, n = 8). The SPE purification cannot completely remove pseudo-carriers in the final dose of [(18)F]FPBM, 1. The concentrations of major pseudo-carriers were measured by UV-HPLC (476-676, 68-95 and 50-71 µg for precursor 3, O-hydroxypropyl and O-allyloxy derivatives, 5 and 6, respectively). To investigate the potential inhibition of SERT binding of these pseudo-carriers, we performed in vitro competition experiments evaluated by autoradiography. Known amounts of 'standard' FPBM, 1, of the pseudo-carriers, 5 and 6, were added to the HPLC-purified [(18)F]1 dose. The inhibition of 'standard' FPBM, 1, binding to the SERT binding sites, using monkey brain sections, were measured (EC50=13, 46, 7.1 and 8.3 nM, respectively for 1, precursor 3, O-hydroxypropyl and O-allyloxy derivative of 3). CONCLUSION: An improved radiolabeling method by a SPE purification for preparation of [(18)F]FPBM, 1, was developed. The results suggest that it is feasible to use this labeling method to prepare [(18)F]FPBM, 1, without affecting in vivo SERT binding.