Mesoporous Alumina (MA) Based Double Column Approach for Development of a Clinical Scale⁹⁹Mo/^99mTc Generator Using (n,γ)⁹⁹Mo: An Enticing Application of Nanomaterial

Abstract

This paper describes the utility of mesoporous alumina (MA), a high capacity nanomaterial based sorbent, for the development of a clinical grade 99Mo/99mTc generator using (n,γ)99Mo. Synthesis of MA was performed using a glucose template in an aqueous system. Structural characterization of the nanosorbent was carried out by analytical techniques such as X-ray diffraction (XRD), small-angle X-ray scattering (SAXS), atomic force microscopy (AFM), scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), thermogravimetry-differential thermal analysis (TG-DTA), Fourier transform infrared (FTIR) spectroscopy, and Brunauer–Emmett–Teller (BET) surface area analysis. The material synthesized was mesoporous and nanocrystalline, with average crystallite size of 2–3 nm with a large surface area of 230 ± 10 m2 g–1. In order to evaluate the surface charge of MA in aqueous solution, the zeta potential was determined at different pH environments. Adsorption characteristics of the sorbent such as time course of the adsorption, distribution ratios of 99Mo and 99mTc ions, Mo sorption capacity under static and dynamic conditions, 99Mo adsorption pattern and 99mTc elution pattern were determined to assess its effectiveness in the preparation of 99Mo/99mTc generator. The measured distribution ratio values indicate that 99Mo is both strongly and selectively retained by MA at acidic pH and 99mTc could be readily eluted from it, using 0.9% NaCl solution. The static sorption capacity and practical sorption capacity under dynamic conditions of MA was determined to be 225 ± 20 and 168 ± 12 mg Mo per gram of sorbent, respectively. With a view to realize the scope of developing clinical scale generator, a novel tandem column generator concept was used in which two 99Mo loaded columns were connected in series. In this method 99mTc eluted from the first column was fed to the second column to achieve higher radioactive concentration (RAC) as well as purity of 99mTc. A 26 GBq (700 mCi) 99Mo/99mTc generator was developed using (n,γ)99Mo having specific activity of ∼18.5 GBq (500 mCi)/g of Mo. The 99mTc eluted from the generator possessed high radionuclidic, radiochemical, and chemical purity and was amenable for the preparation of 99mTc-labeled radiopharmaceuticals. The technology can be adapted by those countries having research reactors with flux >1 × 1014 n·cm–2·s–1 to produce 99Mo by (n,γ) route. The capacity of the generator can be scaled up to 260 GBq (7 Ci) using (n,γ)99Mo produced from a reactor with flux >1 × 1015 n·cm–2·s–1.

Development of Novel Alumina by Solid-State Reaction for 99Mo/99mTc Adsorbent Material

“…The plot of 1/[W((W(Po/P)-1)] and relative pressure can be seen in Figure 2, which is used for the surface area calculation. The calculated SBET was 237.65 m 2 /g, similar with most alumina SBET which is ranging from 200-450 m 2 /g (Chakravarty et al, 2013;Saptiama et al, 2017Saptiama et al, , 2019. Even though the surface area is an important parameter for the adsorption process, the other parameter, for instance, crystal phase and acidity, might also play an important role (Sulaiman et al, 2018).…”

“…However, adsorption study using 99 Mo for these materials has not been performed and the synthesis route was quite sophisticated. Chakravarty et al had developed mesoporous alumina with a simple synthesis method which demonstrates adsorption capacity up to 225±10 mg Mo/g alumina and 99m Tc yield up to 89% (Chakravarty et al, 2013). The main drawback of this project was a double column system for 99 Mo adsorption in the generator package which makes the assembly process more complicated.…”

Synthesis and characterization of mesoporous aluminas with different pore sizes: Application in NiMo supported catalyst for hydrotreating of heavy gas oil

“…4a. All materials show broad peak at 3000-3700 cm −1 corresponding to contribution of hydroxyl groups and water molecules [32]. The peaks at 1550 and 1425 cm −1 are attributed to different vibration modes of Al O Al and Al O bond and are present in all materials.…”

An improved kit formulation for one‐pot synthesis of [99mTc]Tc‐HYNIC‐E[c(RGDfK)]2 for routine clinical use in cancer imaging

“…All other chemicals used were of analytical grade and procured from reputed local manufacturers. For all pre‐clinical investigations, [ 99m Tc]Tc activity in the form of [ 99m Tc]NaTcO 4 solution in physiological saline was obtained from a 1.48 GBq (400 mCi) 99 Mo/ 99m Tc column chromatography generator (NanoTechgen‐1) based on mesoporous alumina sorbent material developed in‐house . For clinical investigations, [ 99m Tc]NaTcO 4 was eluted from a 1.85 GBq (500 mCi) 99 Mo/ 99m Tc column chromatography generator obtained from Isorad Ltd., Israel.…”