Long-Term Evaluation of ‘BARC 68 Ge/ 68 Ga Generator’ Based on the Nanoceria-Polyacrylonitrile Composite Sorbent

Abstract

This article describes the long-term evaluation of a nanoceria-polyacrylonitrile (CeO₂-PAN) composite sorbent-based ⁶⁸Ge/⁶⁸Ga generator reported. This generator used the new CeO₂-PAN composite sorbent for preparation of the ⁶⁸Ge/⁶⁸Ga generator. Since this sorbent has not been previously evaluated, a thorough long-term evaluation of the performance of the generator is necessary to ensure its applicability for clinical practice. The performance of the generator was evaluated in terms of ⁶⁸Ga yield, ⁶⁸Ge breakthrough, radioactive concentration of the ⁶⁸Ga solution, and suitability of the ⁶⁸Ga for the preparation of ⁶⁸Ga-labeled tracers. The ⁶⁸Ge/⁶⁸Ga generator was able to provide a ⁶⁸Ga activity with consistent yields (>70%) and having acceptable radionuclidic (<10⁻⁴% of ⁶⁸Ge breakthrough), radiochemical, and chemical purities for an extended period of time. The eluted ⁶⁸GaCl₃ is useful for the majority of the ⁶⁸Ga complexation chemistry.

Introduction

The ⁶⁸Ge/⁶⁸Ga generator has emerged as a convenient source to provide ⁶⁸Ga in a hospital radiopharmacy for the synthesis of ⁶⁸Ga-labeled radiopharmaceuticals and represents a developmental milestone in the field of PET-based molecular imaging. As a metallic radionuclide, ⁶⁸Ga has great capability to be used for radiolabeling molecular tumor-targeting vectors, such as peptides or proteins (monoclonal antibodies or fragments thereof), through a bifunctional chelator link.^1,2 A number of new ⁶⁸Ga tracers have been developed in the recent past, which is reflected by the continuous increase in research articles from all areas of ⁶⁸Ga-based radiopharmaceutical chemistry.¹

Over the years, a variety of ⁶⁸Ge/⁶⁸Ga generators have been developed using a gamut of sorbents such as Al₂O₃, CeO₂, SnO₂, TiO₂, ZrO₂, and organic matrices.¹ Consequently, ⁶⁸Ga was eluted with different eluents. In spite of remarkable advancements, the low radioactive concentration, high acidity, unacceptable ⁶⁸Ge breakthrough, and the presence of potential metal ion impurities in the generator eluate have emerged as the major deterrents in the path of direct preparation of ⁶⁸Ga-based radiopharmaceuticals. Most of the commercially available ⁶⁸Ge/⁶⁸Ga generator systems demonstrate deteriorating performance in terms of increased ⁶⁸Ge breakthrough and reduced ⁶⁸Ga elution yield on repeated elutions over a prolonged period of time.^2,3 To circumvent these issues, attempts were made to perform postelution processing of the ⁶⁸Ga eluate from the ⁶⁸Ge/⁶⁸Ga generator and a number of purification strategies using anion and cation exchange chromatography and fractionation have evolved, which provide ⁶⁸Ga in acceptable pH free from metallic impurities as well as ⁶⁸Ge breakthrough.^3

–9 However, these additional manipulations are making the studies with ⁶⁸Ga more time-consuming as well as expensive. For these reasons, the availability of ⁶⁸Ge/⁶⁸Ga generators, which can be directly used in the hospital radiopharmacy similar to ⁹⁹Mo/^99mTc generators, is desirable.

In this context, we have reported the results of preliminary studies using the nanoceria-polyacrylonitrile (CeO₂-PAN) composite for fabrication of ⁶⁸Ge/⁶⁸Ga generators, which provided the ⁶⁸Ga eluate free from metallic impurities and exhibited low ⁶⁸Ge breakthrough, which could be used directly for the synthesis of ⁶⁸Ga radiotracers.¹⁰ In this article, we report the 1-year performance evaluation of the CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generator in terms of ⁶⁸Ga yield, ⁶⁸Ge breakthrough, radioactive concentration of the ⁶⁸Ga solution, and suitability of the ⁶⁸Ga for the preparation of ⁶⁸Ga-labeled radiotracers.

Materials

Reagents, such as hydrochloric acid, ammonium hydroxide, and ammonium acetate, used in the studies were of analytical grade procured from the Aldrich Chemical Company. Cerium (III) nitrate (99.9% pure) was purchased from E. Merck. The p-benzyl isothiocyanato derivatives of bifunctional chelators such as diethylenetriaminepentaacetic acid (DTPA-NCS), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NCS), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) and 3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA-NCS) were purchased from Macrocyclics. The RGD peptide conjugate, namely, DOTA-E[c(RGDfK)]₂ (DOTA-RGD₂) was custom synthesized by Ms. ABX Advanced Biochemical Compounds. DOTA-TATE (DOTA⁰-DPhe¹-Tyr³-octreotate, DOTA was obtained from Pi Chem. The structures of the ligands and conjugate peptides used are given in Figure 1. Germanium-68 (⁶⁸Ge) in the HCl medium was obtained from the Atom Hightech Company Limited. All the reagents were dissolved in deionized water (resistivity >18.2 MΩ).

FIG. 1.

Structures of the ligands used for ⁶⁸Ga-labeling (a) DTPA-NCS, (b) DOTA-NCS, (c) NOTA-NCS, (d) PCTA-NCS, (e) DOTA-TATE, and (f) DOTA-RGD₂.

A HPGe detector (Canberra Eurisys) coupled to a multichannel analyzer (MCA) was used for analysis of ⁶⁸Ga. The chemical analysis for the trace level of metal ions was performed using Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-ES JY-238; Emission Horiba Group). UV-visible spectrometry was carried out using the JASCO V-530, UV/Vis the spectrophotometer. The high-performance liquid chromatography (HPLC) system used was obtained from JASCO (PU 1580). A well-type NaI(Tl) scintillation detector was coupled to the system (Model PNS-2, Electronic Enterprises (I) Pvt. Ltd.) for radioactivity measurements in the eluate. All the solvents used were of the HPLC grade and purchased from reputed local manufacturers, degassed, and filtered before use.

Experimental

Synthesis of CeO₂-PAN composite sorbent

The CeO₂-PAN sorbent was prepared by the decomposition of the cerium oxalate precursor to cerium oxide followed by incorporation in the PAN matrix, as described in our earlier article.¹⁰ Several batches (n=10) of CeO₂-PAN were prepared and were subjected to structural characterization as we reported earlier.¹⁰

Development of ⁶⁸Ge/ ⁶⁸Ga generator using CeO₂-PAN sorbent

A 740 MBq (20 mCi) ⁶⁸Ge/⁶⁸Ga generator was prepared adopting the procedure reported earlier.¹⁰ An 8×0.6-cm inner diameter (i.d.) borosilicate glass column, with a sintered disc (G_o) at the bottom was packed with 0.5 g of CeO₂-PAN and maintained in a lead shielded container after preconditioning the material with 0.01 M HCl. All the operations were carried out in the closed cyclic system using connecting tubes. The input and output connections were made with standard Teflon tubings of 1-mm i.d. and connectors. The generator column, connectors, and connection tubings were integrated within a small portable lead shielded unit throughout experimental use for radioprotection purpose. Only the elution vial and output vial were accessible externally. A disposable 0.22-μm membrane filter was attached to the generator column output by Teflon tubing. To avoid the presence of metallic impurities, only Teflon needles were used for connecting the input and output vials. A schematic diagram of the ⁶⁸Ge/⁶⁸Ga generator system is shown in Figure 2. The ⁶⁸Ge/⁶⁸Ga solution containing 740 MBq (20 mCi) of ⁶⁸Ge at pH 2 was percolated into the column maintaining a flow rate of 0.25 mL·min⁻¹. The ⁶⁸Ge-loaded column was washed with 100 mL of the 0.1 M HCl solution, and then dried under vacuum for 1 minute.

FIG. 2.

Schematic diagram of the ⁶⁸Ge/⁶⁸Ga generator assembly.

Evaluation of the performance of the ⁶⁸Ge/ ⁶⁸Ga generator over a period of 1 year

Gallium-68 was periodically eluted from the generator using the 0.1 N HCl solution at a flow rate of 2 mL·min⁻¹. More than 250 elutions were carried out during the 1-year period of study. The generator elution profile was studied by collecting the eluates in fractions of 1 mL volume and determining its activity. The elution profile of the generator was determined at the beginning of each month (Fig. 3). In general, a fractionated elution approach was adopted in which, the first 1–1.5 mL fraction containing a negligible amount of activity was discarded and the subsequent 1.5–2.0 mL fraction containing the major portion of the ⁶⁸Ge activity was used for evaluation as well as radiolabeling studies. The performance of the generator was evaluated for ∼1 year, by periodic elutions at a 24-hour interval (Fig. 4).

FIG. 3.

The elution profiles of the nanoceria-polyacrylonitrile (CeO₂-PAN)-based ⁶⁸Ge/⁶⁸Ga generator over the period of 1 year: each curve indicated by numbers indicates the profile at the beginning of that month.

FIG. 4.

Elution performance of the ⁶⁸Ge/⁶⁸Ga generator over a period of 1 year: the generator was eluted at 24-hour intervals and the data points at 10-day intervals are indicated in the figure.

The activity of ⁶⁸Ga was measured using a precalibrated HPGe detector coupled with an MCA. The measured activity of ⁶⁸Ga after allowing time ‘t’ for its growth, is denoted by A_s(t), and the elution yield is calculated by using the following equation: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} \begin{align*}Elution \ yield ( \% ) = \frac { A_s ( t ) } { A_1^0 \left( 1 - e^ { - \lambda_2 t } \right) } \times 100\end{align*} \end{document}

where A₁° is the activity of ⁶⁸Ge and λ₂ is the decay constant of ⁶⁸Ga. The ⁶⁸Ge contamination level in ⁶⁸Ga was quantified by allowing the separated ⁶⁸Ga samples to decay for 2 days, and then measuring the 511 keV γ-peak of ⁶⁸Ga daughter. This, in turn, corresponds to the level of the ⁶⁸Ge contaminant.

To determine the presence of potential chemical impurities (in the form of Ce, Cu, Fe, Al, and Mn ions) in the ⁶⁸Ga eluate, the ⁶⁸Ga samples were allowed to decay for 7 days. The trace levels of the metal ion contamination in the decayed samples were determined by ICP-AES analysis. The calibration curves for these ions were obtained by using standard solutions having known concentrations of these ions. The presence of trace levels of organic impurities that are likely to result from radiation degradation of the polyacrylonitrile was tested by UV-visible spectrometry using the decayed ⁶⁸Ga samples, as reported earlier.¹⁰ The chemical purity of the ⁶⁸Ga eluate was determined by random selection of ⁶⁸Ga samples over this period of time.

Preparation of the complexes of ⁶⁸Ga with various ligands

Various bifunctional chelators (DOTA-NCS, DTPA-NCS, NOTA-NCS, and PCTA-NCS) and DOTA-conjugated peptides (DOTA-TATE, DOTA-RGD₂) were radiolabeled with ⁶⁸Ga availed from the generator, adopting the procedure reported earlier.^10
–12 The respective ligand solution (20 μL) of concentration 1 μg/μL in HPLC grade water was mixed with 300 μL of 0.1 M ammonium acetate buffer (pH ∼5) and 200 μL of the ⁶⁸Ga eluate was then added. The pH of the resulting mixture was found to be ∼4. In case of DOTA- and DTPA-based ligands, the reaction mixtures were incubated 353 K for 15 minutes, while the NOTA- and PCTA-based ligands were incubated at room temperature for 5 minutes. The complexation yields were determined by the HPLC technique (Fig. 5).

FIG. 5.

The typical radio-HPLC patterns of (a) ⁶⁸Ga-DTPA-NCS, (b) ⁶⁸Ga-DOTA-NCS, (c) ⁶⁸Ga-NOTA-NCS, (d) ⁶⁸Ga-PCTA-NCS, (e) ⁶⁸Ga-DOTA-TATE, and (f) ⁶⁸Ga-DOTA-RGD₂ complexes.

HPLC of the ⁶⁸Ga complexes was performed using a dual pump HPLC unit with a C-18 reversed phase HiQ-Sil (5 μM, 25×0.46 cm) column. The elution was monitored both by detecting the UV signal at 254 nm as well as the radioactivity signal using a NaI(Tl) detector. Water (A) and acetonitrile (B) mixtures with 0.1% trifluoroacetic acid were used as the mobile phase. The flow rate was maintained at 1 mL·min⁻¹.

Results

Synthesis of CeO₂-PAN composite sorbent

The preparation of the nanoceria by decomposition of the cerium oxalate precursor and its subsequent immobilization in PAN constitutes a preconceived strategy of availing an engineered form of nanoceria amenable for column operation. The structural characterization studies were carried out, not only to ensure the quality of the material, but also to predict any inter batch variation and, thus, to demonstrate the reproducibility of the synthesis protocol. The structural characterization studies revealed that the material was nanocrystalline in the cubic phase, consisting of agglomerated particles (mean agglomerate size ∼23 μm), consisting of primary particles of about 10–12 nm, and possessing a surface area of 75±6 m²·g⁻¹ (n=10). The synthesis yield as well as structural characteristics of the nanosorbent remained practically unchanged from batch to batch indicating the dependability and reproducibility of the synthesis procedure.

Development of the ⁶⁸Ge/ ⁶⁸Ga generator and evaluation of its performance over a period of 1 year

A 740 MBq (20 mCi) ⁶⁸Ge/⁶⁸Ga generator (Fig. 2) was prepared and ⁶⁸Ga was eluted regularly at 24-hour intervals, over a period of 1 year for radiotracer production. The elution profile of the generator was studied at the beginning of each month and the results obtained over the period of 1 year are illustrated in Figure 3. An examination of the elution profiles in Figure 3 reveals that the elution profiles obtained were quite sharp throughout the period of elution for 1 year. A close scrutiny of the elution profiles reveal that only a low percentage of activity (<5%) was eluted in the first 1.5 mL fraction and the majority of radioactivity was eluted in subsequent 1.5–2.0 mL fractions. This helped to provide the ⁶⁸Ga eluate with a maximum radioactive concentration throughout the useful life of the generator. In case of the commercial ⁶⁸Ge/⁶⁸Ga generators, 4–6 mL of the HCl solution was required for elution of ⁶⁸Ga with >80% yield.^4,13 The concept of fractionated elution seemed attractive as it was possible to elute ⁶⁸Ga with high radioactive concentrations and at the same time circumvent the broadening of the elution profiles without much loss of activity. After 8 months of continuous operation, a slight broadening in the subsequent elution profiles was noted, however, ⁶⁸Ga elution yields remained high (Fig. 4).

The elution performance of the generator over the span of a 1-year operation is shown in Figure 4 (data points shown at 10-day intervals). An examination of the results demonstrates that for the first few months of operation, the elution yield of ⁶⁸Ga was found to be ∼85%, which gradually decreased to ∼70%. The gradual decrease in the elution yield of ⁶⁸Ga from ∼85% to ∼70% seems to be due to the impact of structural transformation of the sorbent matrix over a prolonged period of time. Structural transformation emerged as the impediment for the diffusion of the ⁶⁸Ga ions from the interior surface of the sorbent matrix to the solution phase and its effect is manifested in terms of reduction in the elution yield. The determination of the nature and extent of the structural transformation would require further studies and is beyond the scope of this investigation. It is pertinent to note that the magnitude of decrease in the elution yield is significantly lower than that observed with commercial generators, where the elution yield decreases to ∼50% of the initial value.²

The ⁶⁸Ge breakthrough from the generator was measured regularly and the data points at 10-day intervals are shown in Figure 4. The breakthrough of ⁶⁸Ge in the ⁶⁸Ga eluate was negligibly low (<10⁻⁴%) and it remained unchanged over the period of 1 year. The breakthrough of ⁶⁸Ge from the CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generator was significantly lower than that is observed with commercial ⁶⁸Ge/⁶⁸Ga generators, where the level of ⁶⁸Ge impurity in ⁶⁸Ga varies between 10⁻²%–10⁻³%.^4,13 The ICP-AES analysis of the randomly selected decayed samples of ⁶⁸Ga revealed that the level of Ce, Fe, Cu, Mn, and Al ions was always <0.1 ppm. Owing to the unavailability of instrumental facility to analyze radioactive samples, elemental analysis of Zn ions in the freshly eluted ⁶⁸Ga samples could not be carried out. The generator eluate was also found to be free from other metal ion impurities that could interfere in Ga(III) complexation chemistry. In contrast, metal ion impurities such as Fe, Cu, Al, Zn, Sn, Ti, and Mn are detected in the ⁶⁸Ga eluate from the commercial ⁶⁸Ge/⁶⁸Ga generators and the level of each of these metal ions vary between 1 and 10 ppm.^2,3,5 From analysis of the UV-visible spectra of decayed ⁶⁸Ga samples, it could be inferred that PAN residue was not present in the ⁶⁸Ga eluate, as no absorption was observed at 278 nm, which corresponds to the characteristic n-π* transition of nitrile groups.¹⁴

Preparation of the complexes of ⁶⁸Ga with various ligands

The complexation yields of ⁶⁸Ga with different ligands obtained using ⁶⁸Ga eluted from the generator are summarized in Table 1. All the radiolabeling studies were carried out by using ⁶⁸Ga directly eluted from the generator, without any postelution purification or concentration step. It is evident from the results that ⁶⁸Ga eluted from the generator could be successfully utilized for the preparation of the complexes with >95% yields. These radiolabeling studies were planned and carried out when the generator was more than 300 days old. The complexation yields of ⁶⁸Ga-complexes were determined by radio-HPLC analysis. The retention times of the ⁶⁸Ga-complexes observed in the HPLC technique used are also given in Table 1. Uncomplexed ⁶⁸GaCl₃ was eluted within 2.5 minutes for both the solvent systems used. The typical radio-HPLC patterns of ⁶⁸Ga-complexes studied are given in Figure 5.

Table 1.

Complexation Yields of Different Ligands with ⁶⁸ Ga

Complex	HPLC elution system	Retention time (min)	Yield (%)
⁶⁸Ga-DOTA-NCS	I	5.8	98 ± 2
⁶⁸Ga-DTPA-NCS	I	4.6	98 ± 2
⁶⁸Ga-NOTA-NCS	I	5.9	99.5 ± 0.2
⁶⁸Ga-PCTA-NCS	I	7.5	97 ± 1
⁶⁸Ga-DOTA-TATE	II	16.1	96 ± 2
⁶⁸Ga-DOTA-RGD₂	II	15.7	95 ± 1

I: 0–5 min 100% A, 5–15 min 100% A to 90% A, 15–16 min 90% A to 100% A, 16–20 min 100% A. II: 0–5 min 95% A, 5–15 min 95% A to 5% A, 15–20 min 5% A, 20–25 min 5% A to 95% A, 25–30 min 95% A. Where A: 0.1% trifluoroacetic acid in water and B: 0.1% trifluoroacetic acid in acetonitrile (n = 10, ‘±’ indicates standard deviation).

The maximum activity of ⁶⁸Ga that was used for the preparation of the complexes was 185 MBq (5 mCi), which is equivalent to one patient-dose of ⁶⁸Ga-based radiopharmaceuticals that are commonly used in Nuclear Medicine Departments.^15,16 Accordingly, the maximum specific activity of ⁶⁸Ga-complexes that could be achieved was ∼9 MBq/μg of ligand.

Discussion

The use of ⁶⁸Ga-labeled tracers together with the development of small tumor-affine peptides targeting somatostatin receptors has not only changed the diagnostic approach to neuroendocrine tumors, but also opened unlimited potential for exploring the development of ⁶⁸Ga tracers for molecular imaging applications. With the rapid advances in the development and clinical use of ⁶⁸Ga radiopharmaceuticals and the exciting perspective of the ⁶⁸Ga radiopharmacy, the need for a user friendly ⁶⁸Ge/⁶⁸Ga generator without the necessity of postpurification attachment, similar to the ⁹⁹Mo/^99mTc generator to meet the expectations of clinicians is imminent. The development of optimal sorbents for the ⁶⁸Ge/⁶⁸Ga generator is an important task. For commercial generator production, Cyclotron Ltd., Obninsk, Russian Federation uses a modified TiO₂ phase,¹⁷ the Eckert & Ziegler Isotope Products uses titanium dioxide (IGG 100),¹⁸ and iThemba, Republic South Africa uses a SnO₂.^4,19 While the utilities of these sorbents constitute a successful paradigm for fabrication of ⁶⁸Ge/⁶⁸Ga generators, the presence of metal ion impurities as well as ⁶⁸Ge breakthrough in the ⁶⁸Ga eluate necessitates a postelution purification procedure. The presence of the ⁶⁸Ge activity in the eluate of the ⁶⁸Ge/⁶⁸Ga generator, although low, has been a point of concern for clinical application of ⁶⁸Ga-labeled pharmaceuticals because Ge is rapidly absorbed after oral, subcutaneous, intramuscular, or intraperitoneal administration and could be a potential long lived contaminant in a patient for years.²⁰

The elution yield of ⁶⁸Ga from the CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generator varied between 70%–85% and the breakthrough of ⁶⁸Ge in the ⁶⁸Ga eluate was negligibly low (<10⁻⁴%). These values remained consistent over a period of 1 year. In contrast, the elution efficiency of the commercial generators decreased to half of the initial value (∼80%) after 100–200 elutions.² In addition, the values for ⁶⁸Ge breakthrough increase to ∼10⁻²% on repeated elution over a prolonged period of 1 year.² The scope of using CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generators seemed very attractive as it not only provides consistent performance over a prolonged period of time, but also precludes the requirement of postprocessing procedures for concentration and purification of ⁶⁸Ga. Realization of this paradigm-changing ⁶⁸Ge/⁶⁸Ga generator represents a cost-effective proposition for assessing ⁶⁸Ga to meet future research and clinical demands.

The radiolabeling yields of different bifunctional chelators as well as conjugated peptides with ⁶⁸Ga was found to be >98% even while ⁶⁸Ga eluted after 9 months of the generator was used in these studies. The breakthrough capacity of CeO₂-PAN sorbent was determined to be 20±2 mg Ge per g of sorbent in our earlier investigation.¹⁰ This result reflects that even a small column containing 500 mg of the CeO₂-PAN sorbent (as used for the preparation of the present generator) would offer the scope of making a 9.25 GBq (250 mCi) ⁶⁸Ge/⁶⁸Ga generator. However, further investigations are required to evaluate the effect of radiation on the performance of the CeO₂-PAN sorbent containing high activity of ⁶⁸Ge before such generators can be used in the clinical context.

Owing to the reported enhanced radiation stability of nanocrystalline metal oxides compared to their bulk counterparts²¹ as well as PAN-based composite materials,^22,23 it is anticipated that the CeO₂-PAN sorbent would resist radiation degradation. Therefore, it is plausibly assumed that issues regarding radiation stability of this sorbent can be addressed to prepare high-activity ⁶⁸Ge/⁶⁸Ga generators suitable for clinical applications.

Conclusion

The CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generator is an important development to provide ⁶⁸Ga of adequate radioactive concentration free from not only metal impurities that could interfere in Ga(III) complexation chemistry, but also providing consistently low ⁶⁸Ge breakthrough. The long-term performance evaluation of the CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generators has demonstrated consistently high elution yields (>70%) and provided ⁶⁸Ga with minimal metal contamination and acceptable ⁶⁸Ge breakthrough, which is in contrast to what is observed in case of commercial generators, which show degrading performance in terms of decreasing elution yield and increasing ⁶⁸Ge breakthrough on repeated elutions over a prolonged period of time. The ⁶⁸Ga eluate while used for complexation studies with different ligands and conjugated peptides gave high complexation yields.

This indigenous CeO₂-PAN-based ⁶⁸Ge/⁶⁸Ga generator represents a new paradigm, and a quality compliance with current codes of good (pharmaceutical) manufacturing practices (cGMP) for parametric release of ⁶⁸Ga as an approved pharmaceutical ingredient for clinical use is essential. Having successfully completed the demonstration studies, regulatory approval of the generator will be taken up shortly. As this investigation contains scientific data that could provide an insight into the various stages of the entire process, the measures to ensure safety and evidence on the quality of separated ⁶⁸Ga for clinical applications, these could be used as supporting data for obtaining regulatory approval.

It is anticipated that CeO₂-PAN as a sorbent would interest other users to develop ⁶⁸Ge/⁶⁸Ga generators, which are more user friendly and cost effective using the same or similar sorbents. We believe that local availability of a simple-to-handle ⁶⁸Ge/⁶⁸Ga generator at an affordable cost would facilitate more research on new radiopharmaceuticals with ⁶⁸Ga and promote the beneficial use of ⁶⁸Ga for imaging in the country. There is a great deal of anticipation that the BARC ⁶⁸Ge/⁶⁸Ga generator will find its way into many more institutions in India to offer cost-effective molecular imaging service in the foreseeable future.

Footnotes

Disclosure Statement

No competing financial interests exist.

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Long-Term Evaluation of ‘BARC 68 Ge/ 68 Ga Generator’ Based on the Nanoceria-Polyacrylonitrile Composite Sorbent

Abstract

Introduction

Materials

Experimental

Synthesis of CeO2-PAN composite sorbent

Development of 68Ge/ 68Ga generator using CeO2-PAN sorbent

Evaluation of the performance of the 68Ge/ 68Ga generator over a period of 1 year

Preparation of the complexes of 68Ga with various ligands

Results

Synthesis of CeO2-PAN composite sorbent

Development of the 68Ge/ 68Ga generator and evaluation of its performance over a period of 1 year

Preparation of the complexes of 68Ga with various ligands

Discussion

Conclusion

Footnotes

Disclosure Statement

References

Synthesis of CeO₂-PAN composite sorbent

Development of ⁶⁸Ge/ ⁶⁸Ga generator using CeO₂-PAN sorbent

Evaluation of the performance of the ⁶⁸Ge/ ⁶⁸Ga generator over a period of 1 year

Preparation of the complexes of ⁶⁸Ga with various ligands

Synthesis of CeO₂-PAN composite sorbent

Development of the ⁶⁸Ge/ ⁶⁸Ga generator and evaluation of its performance over a period of 1 year

Preparation of the complexes of ⁶⁸Ga with various ligands