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Copyright of Journal of Isotopes is the property of Journal of Isotopes Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: 68Ga has a half-life of 68 minutes, with 89% of its decay is through positron emission. It is available from generator systems and possesses suitable property for labeling radioligands. These aspects make 68Ga a promising tracer for positron emission tomography (PET) imaging. This study aims to develop the purification process of the 68Ga eluates from 68Ge/68Ga generator after its recommended shelf-life and ensuring the quality through the radiolabeling process. Materials and Methods: In this study, we explored the development of a purification method for 68Ga eluted from a 68Ge/68Ga generator before radiolabeling was investigated. Cation and anion exchange chromatography techniques were combined to remove trace amounts of competing metal ion impurities. Post-purification, the eluate’s metal contents were analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Breakthrough of 68Ge was measured using a multi-channel analyzer (MCA) spectrometer with high-purity germanium (HPGe) radiation detectors. Additionally, the radiochemical purity of 68Ga-NOTA-RGD was analyzed by high-performance liquid chromatography (HPLC). Results: Metal impurities including Fe(II), Zn(II) and Al(III) were reduced by 61%, 38% and 44% respectively. The 68Ge breakthrough was approximately ~10–3%. The labeling efficiency with NOTA-RGD, a tracer for angiogenesis imaging, resulted in an average yield of 68Ga-NOTA-RGD (not corrected for decay) of around 50%, with a radiochemical purity by HPLC of approximately 98%–99%. Conclusion: Cation exchange in combination with anion exchange chromatography was thus proven to be an efficient method for purification of the 68Ga eluate from a 68Ge/68Ga generator prior to labeling the 68Ga PET radiotracer. [ABSTRACT FROM AUTHOR]

In this study, a standardized preparation process for 68Ga-PSMA-11 injection was developed by optimizing the labeling conditions, and the quality control standards of 68Ga-PSMA-11 injection applicable to our institution were formulated by combining domestic and international pharmacopoeias. Reviewing the preparation and quality control results of a total of 316 batches of 68Ga-PSMA-11 injections from 2020—2022, it was found that all batches were successfully prepared to obtain 68Ga-PSMA-11 injections, and the quality control results were in full compliance with the proposed standards. The labeling rate of 68Ga-PSMA-11 was （85.3±11.4）%, and it was decreased significantly with increasing total elution volume of 68Ge/68Ga generator, while the elution interval time had little effect on the labeling rate. This study is expected to guide nuclear medicine practitioners to standardize the preparation and quality control process of 68Ga-PSMA-11 injection, thus improving the quality and safety of the drug, and providing a reference for related industry standards.

Objective: 68Ga has a half-life of 68 minutes, with 89% of its decay is through positron emission. It is available from generator systems and possesses suitable property for labeling radioligands. These aspects make 68Ga a promising tracer for positron emission tomography (PET) imaging. This study aims to develop the purification process of the 68Ga eluates from 68Ge/68Ga generator after its recommended shelf-life and ensuring the quality through the radiolabeling process. Materials and Methods: In this study, we explored the development of a purification method for 68Ga eluted from a 68Ge/68Ga generator before radiolabeling was investigated. Cation and anion exchange chromatography techniques were combined to remove trace amounts of competing metal ion impurities. Post-purification, the eluate’s metal contents were analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Breakthrough of 68Ge was measured using a multi-channel analyzer (MCA) spectrometer with high-purity germanium (HPGe) radiation detectors. Additionally, the radiochemical purity of 68Ga-NOTA-RGD was analyzed by high-performance liquid chromatography (HPLC). Results: Metal impurities including Fe(II), Zn(II) and Al(III) were reduced by 61%, 38% and 44% respectively. The 68Ge breakthrough was approximately ~10–3%. The labeling efficiency with NOTA-RGD, a tracer for angiogenesis imaging, resulted in an average yield of 68Ga-NOTA-RGD (not corrected for decay) of around 50%, with a radiochemical purity by HPLC of approximately 98%–99%. Conclusion: Cation exchange in combination with anion exchange chromatography was thus proven to be an efficient method for purification of the 68Ga eluate from a 68Ge/68Ga generator prior to labeling the 68Ga PET radiotracer.

Objective: 68Ga can be routinely produced by a 68Ge/68Ga generator without the need for a cyclotron. It is recommended to replace the 68Ge/68Ga generator after 250 elutions or 12 months of shelf-life whichever endpoint is reached first. However, a 68Ge/68Ga generator that has gone past its recommended lifespan can still be further used as a 68Ga source for 68Ga-labeled radiopharmaceuticals for use in animal experiments. To ensure the quality of 68Ga eluates, we aimed to evaluate the efficacy and safety of the ITM (Isotope Technologies München) 68Ge/68Ga generator in our institute after its recommended shelf-life. Materials and Methods: A 21-month-old ITM 68Ge/68Ga generator was eluted using 4.0 ml of 0.05 M HCl. The 68Ga elution yields were calculated, and 68Ge breakthrough was measured at least 48 h after elution in an aliquot amount using a multichannel analyzer (MCA) with a high-purity germanium probe. Metal impurities in the 68Ga eluates were analyzed by ICP-MS. Results: The elution yield of 68Ga was 35.2 ± 8.1%; n = 5 (decay corrected). 68Ge breakthrough from the ITM 68Ge/68Ga generator was below the detectable level. The average amounts of the metallic ions 57Fe, 66Zn, 203Pb, 60Ni, and 63Cu were 18.60, 9.86, 2.42, 0.52, and 0.47 µg/GBq, respectively. Conclusion: The ITM 68Ge/68Ga generator demonstrated consistent and reliable 68Ga elution profiles with an absence of either 68Ge breakthrough or other metal contaminants in the eluent samples as verified by the manufacturer. The use of the ITM 68Ge/68Ga generator could be extended past its recommended shelf-life to prepare 68Ga radiopharmaceuticals that are considered safe and suitable for use in animal experimentation and other applications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Isotopes is the property of Journal of Isotopes Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: 68Ga can be routinely produced by a 68Ge/68Ga generator without the need for a cyclotron. It is recommended to replace the 68Ge/68Ga generator after 250 elutions or 12 months of shelf-life whichever endpoint is reached first. However, a 68Ge/68Ga generator that has gone past its recommended lifespan can still be further used as a 68Ga source for 68Ga-labeled radiopharmaceuticals for use in animal experiments. To ensure the quality of 68Ga eluates, we aimed to evaluate the efficacy and safety of the ITM (Isotope Technologies München) 68Ge/68Ga generator in our institute after its recommended shelf-life. Materials and Methods: A 21-month-old ITM 68Ge/68Ga generator was eluted using 4.0 ml of 0.05 M HCl. The 68Ga elution yields were calculated, and 68Ge breakthrough was measured at least 48 h after elution in an aliquot amount using a multichannel analyzer (MCA) with a high-purity germanium probe. Metal impurities in the 68Ga eluates were analyzed by ICP-MS. Results: The elution yield of 68Ga was 35.2 ± 8.1%; n = 5 (decay corrected). 68Ge breakthrough from the ITM 68Ge/68Ga generator was below the detectable level. The average amounts of the metallic ions 57Fe, 66Zn, 203Pb, 60Ni, and 63Cu were 18.60, 9.86, 2.42, 0.52, and 0.47 µg/GBq, respectively. Conclusion: The ITM 68Ge/68Ga generator demonstrated consistent and reliable 68Ga elution profiles with an absence of either 68Ge breakthrough or other metal contaminants in the eluent samples as verified by the manufacturer. The use of the ITM 68Ge/68Ga generator could be extended past its recommended shelf-life to prepare 68Ga radiopharmaceuticals that are considered safe and suitable for use in animal experimentation and other applications.

Objective: The presence of metallic impurities can pose a serious concern due to their interaction with receptor-specific biomolecules that require the highest possible specific activity, especially in radioactive labeling. There are studies in which Zn and other toxic metal pollution increases if the generator is not used for a long time. In this study the effect of pre-elution on chemical and radiochemical impurities in the synthesis product was investigated. Material and Methods: In the study, 68GaPSMA-11 labeling was performed with the generator eluate that was not used for one month (sample 1). A blank elution was taken 24 hours after using the generator (sample 2). In the next 24 hours, the second 68GaPSMA-11 labeling was performed (sample 3). Six hours after this labeling, another 68GaPSMA-11 synthesis was performed (sample 4). Eluates were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: Results was reported as a table in μg/ml. 68Ge levels determined at 0.018 ppm, 0.012 ppm and 0.009 ppm levels in the labeled products were determined below the pharmacopoeia limits. Zn(II) impurities were found as 0.625 ppm in the labeling performed without generator pre-elution. In generator preeluted labelings; Zn(II) impurities were determined as 0.133 ppm and 0.108 ppm. Conclusion: Pre-elution of the generator prior to synthesis does not seem to be a chemical requirement other than zinc pollution. 68GaPSMA-11 can be pre-eluted for high labeling efficiency, but it is thought that pre-elution is not significant in terms of chemical and radiochemical contamination. [ABSTRACT FROM AUTHOR]

Nowadays, due to thesuitable decay characteristics and possible production of 68Ga independent of the cyclotron in the form of 68Ge/68Ga generator with reasonable cost, this radionuclide is known as a suitable choice for PET imaging. Recently, SnO2 based 68Ge/68Ga generator was successfully prepared in Iran. In this study, in order to investigate the possible utilization of the made generator in the production and development of 68Ga-based diagnostic radiopharmaceuticals and optimal usage of the generator in the clinical applications, the main characteristics of the generator including the selection of appropriate eluent, elution profile and elution yield were determined, and radionuclidic, chemical and radiochemical purity of the eluate were evaluated. The results of this study indicated that the characteristics of the developed generator in Iran is comparable to those 68Ge/68Ga generators in other countries and it has suitable performance for the usage of developing 68Ga-based PET radiopharmaceuticals.

Objectives: Germanium-68/gallium-68 (68Ge/68Ga) generator eluate contains a number of metal cations that can compete with 68GaCl3, reducing specific radioactivity. The first step in peptide labeling with 68GaCl3 is to remove 68Ge and several other metals with a long half-life. In this purification step, the elution residue that is passed through the cartridge is collected in glass waste bottles. Waste management is included in good production practices, and in particular, the activity of long half-life 68Ge (270.95 days) and other toxic metal levels need to be examined. Our objective in this study is to determine the 68Ge activity in liquid waste produced by the generation of 68Ga and heavy metal concentrations from the generator column materials and to assess whether it can be disposed of as normal waste. Methods: Liquid wastes produced by passing the 68Ge/68Ga generator eluate of 2 different identities via PSH+ cartridge have been analyzed with the inductively coupled plasma mass spectrometry device in the advanced technology application and research center of our university. Results: The average of the 68Ge radioactive pollution was estimated to be 0.142 ppm (µg.mL-1) in the liquid waste analysis after passing through the PSH+ cartridge in the pre-elution in the GalluGEN brand generator. While there was no tin (Sn) impurity, it was determined that the average zinc (Zn) was 1.95 ppm (µg.mL-1) and the average aluminum (Al) impurity was 10.95 ppm (µg.mL-1). While no 68Ge radioactive pollution was determined in the iThemba LABS brand generator, the average Sn was 0.098 ppm (µg.mL-1), average Zn 48.6 ppm (µg.mL-1), and average Al impurity 4.135 ppm (µg.mL-1). Conclusion: All 68Ge/68Ga generators produced have their own certificates. Metallic contamination in the postmarking waste of 68Ge/68Ga generators can be different. It would be a safe method to keep these wastes in place until they are dumped into the sewage systems, given their half-lives in terms of long half-life radioactive metallic contamination. [ABSTRACT FROM AUTHOR]

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8, Met(O2)11]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO2 generator matrix as well as preliminary results on the adaptability to produce [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi8, Met(O2)11]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP mixed with [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP. [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP providing sufficient activity for 1–2 human doses. The resultant formulation of [68Ga]Ga-/[213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi8, Met(O2)11]SP—a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP and [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.

A durable and ready to use 68Ge-68Ga generator column material is required for its routine use in radiopharmaceutical procedures. The present work comprises preliminary studies for development and evaluation of chitosan-TiO 2 based microsphere (C-TOM) composite towards its competence as a column material. The batch uptake studies showed higher distribution coefficients for 68Ge vis-à-vis 68Ga in the complete concentration range of HCl examined (0.01–1 mol.L−1). Furthermore, C-TOM showed enduring physical and chemical stability in 0.01 mol.L−1 HCl with persistent 68Ga elution profiles (>95%) and negligible 68Ge breakthrough (2 × 10−4%) for the preliminary evaluation period of ∼2 months. Overall, the studies indicated that, 68Ga with high radionuclidic purity (≥99.99%) can be eluted routinely in a small volume (∼1.5 mL) of 0.01 mol.L−1 HCl proving its potentials as a novel solid phase extractant for 68Ge/68Ge generator system. Image 1 • Novel approach towards synthesis of chitosan-TiO 2 microsphere (C-TOM). • Superlative physical and chemical stability of C-TOM in 0.01 M HCl. • Separation of 68Ga from 68Ge with high radionuclidic purity. • Consistent 68Ga elution profile with low 68Ge breakthrough. • Possible application of C-TOM as a potential 68Ge/68Ga generator material. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-BPAMD has recently emerged as one of the preferred radiopharmaceuticals for imaging of bone lesions due to its ability to produce high-resolution images and uncomplicated availability of 68Ga, a positron emission tomography (PET) radionuclide, from commercial 68Ge/68Ga generators. The primary objective of this work is to develop freeze-dried BPAMD kit, for the easy and convenient formulation of 68Ga-BPAMD patient dose at the hospital radiopharmacy. In addition, the kit should be compatible with 68Ga, eluted using HCl of various molarities from the 68Ge/68Ga generators sourced from different suppliers.Procedures: Freeze-dried BPAMD kit, comprising 50 μg of BPAMD and 150 mg of HEPES, was prepared and evaluated using 68Ga eluted from three different 68Ge/68Ga generators. Radiochemical purity (RCP) of 68Ga-BPAMD was determined by both thin-layer chromatography and high-performance liquid chromatography studies. The maximum volume of 68Ga, which can be added in the kit, was determined. The biological behavior of 68Ga-BPAMD, prepared using the freeze-dried kit, was evaluated by both in vitro and in vivo studies. Clinical studies were also performed in limited number of patients suffering from metastatic bone cancer.Results: 68Ga-BPAMD could be prepared with >95% RCP using the freeze-dried BPAMD kit and 68Ga eluted from 68Ge/68Ga generators obtained from three different suppliers. 68Ga-BPAMD, prepared using the freeze-dried kit, exhibited adequate serum stability and ∼91% binding with the hydroxyapatite particles. Biodistribution studies in normal Wistar rats exhibited selective uptake of the agent in skeleton and fast clearance of the nonaccumulated activity through urinary route. Clinical studies in cancer patients showed excellent accumulation of the agent in bone lesions.Conclusion: The preliminary studies exhibited the potential of the developed BPAMD kit toward its utilization for the PET scanning of skeletal metastases. [ABSTRACT FROM AUTHOR]

We report column material for a 68Ge/68Ga generator with acid resistance and excellent adsorption and desorption capacity of 68Ge and 68Ga, respectively. Despite being a core element of the 68Ge/68Ga generator system, research on this has been insufficient. Therefore, we synthesized a low molecular chitosan-based TiO2 (LC-TiO2) adsorbent via a physical trapping method as a durable 68Ge/68Ga generator column material. The adsorption/desorption studies exhibited a higher separation factor of 68Ge/68Ga in the concentration range of HCl examined (0.01 M to 1.0 M). The prepared LC-TiO2 adsorbent showed acid resistance capabilities with >93% of 68Ga elution yield and 1.6 × 10−4% of 68Ge breakthrough. In particular, the labeling efficiency of DOTA and NOTA, by using the generator eluted 68Ga, was quite encouraging and confirmed to be 99.65 and 99.69%, respectively. Accordingly, the resulting behavior of LC-TiO2 towards 68Ge/68Ga adsorption/desorption capacity and stability with aqueous HCl exhibited a high potential for ion-exchange solid-phase extraction for the 68Ge/68Ga generator column material.

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga–DOTA–NT and 177Lu–DOTA–NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga–DOTA–NT and 48 h for 177Lu–DOTA–NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga–DOTA–NT, the amount of non-specific binding of neurotensin and the effect of 177Lu–DOTA–NT on HT–29 cells. In vivo biodistribution of 68Ga–DOTA–NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu–DOTA–NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow.

Objective(s): In nuclear medicine studies, gallium-68 (68Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. Methods: 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. Results: 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, FeConclusion: This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country.

Somatostatin receptor positron emission tomography-computed tomography (PET/CT) with 68Ga-1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) peptides have become an indispensable part of disease assessment in patients with neuroendocrine tumors and forms the basis of personalized therapy with peptide receptor-based radionuclide therapy. With growing utilization of PET/CT in developing countries, availability of the indigenous GMP-certified 68Ge/68Ga generators is expected to further promote cost-effective molecular imaging service to the cancer patients. We present our initial clinical experience in 32 patients injected with 68Ga-DOTA-NOC prepared using 68Ga eluted from Bhabha Atomic Research Centre nanoceria-polyacrylonitrile sorbentbased 68Ge/68Ga generator and freeze-dried DOTA-NOC cold kits. [ABSTRACT FROM AUTHOR]

Objective(s): In nuclear medicine studies, gallium-68 (68Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. Methods: 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370℃, followed by biodistribution studies in rats for 120 min. Results: 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, Fe<0.3 ppm and Zn<0.2 ppm) within 15 min at 500℃. The biodistribution of 68Ga-citrate was consistent with former reports up to 120 minutes. Conclusion: This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country. [ABSTRACT FROM AUTHOR]

Different routes can be used to produce the PET isotope 68Ga by proton reactions on different targets. The experimental excitation functions for the reactions 68Zn( p, n) and 72Ge( p, nα) were collected from previous studies and compared with each other, for each reaction, in order to get the most trusted data. Some data were excluded because they gave either too high or too low cross section values. The others were averaged together to give a kind of trusted data set for the production of this important radioisotope. The production of the radionuclide 68Ge, used in the generator 68Ge/68Ga, through proton reactions was also discussed in the same manner. Model calculations of excitation functions of the above mentioned reactions were performed, using both TALYS-1.4 and EMPIRE-3.1 codes, and the results were compared with the averaged experimental data. Some statistical parameters were introduced to control the quality of the overlapping between experimental data and model calculations. The integrated yields for the different reactions leading to 68Ga were estimated. The various routes were discussed on the basis of the given results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 68Ge was produced by natZn(α,xn)68Ge reaction and its production yield was 31.82kBq/μAh (0.86μCi/μAh) at the end of irradiation (EOI). A simple chromatographic method using a SnO2 column was employed to separate 68Ge from the target material and the co-produced non-isotopic radioisotope impurities. 68Ge retained in the column served as the 68Ge/68Ga generator. Elution efficiency of the column was about 60%. First 2ml of the eluate contained more than 95% of the elutable activity. Post-elution purification cum concentration was done with a small cation exchange resin column. The presence of the inactive tin ions in the 68Ga eluate was determined by the ICP-OES technique and was found to be about 0.03ppm. Radiochemical purity of the final 68Ga preparation was more than 99.99% and it was found to be suitable for making complex with ethylenediamine-N,N,N′,N′-tetrakis(methylene phosphonic acid) (EDTMP). [Copyright &y& Elsevier]

Targets withstanding high beam power for production of 68Ge by proton irradiation of Ga were developed using electrodeposition of Ga/Ni alloy (70/30%) on thick Cu backings. Cross sections for reactions, induced by protons (up to 36MeV) and deuterons (up to 50MeV), producing γ-emitting radioisotopes with half-lives longer than 2 h were measured in a stacked-foil irradiation using thin Ga/Ni targets produced with this technique. Excitation functions for 68,69Ge are discussed, relative to the monitor reactions natCu(p, x)62Zn or natAl(d, x)24,22Na. The results are compared to the scarce literature values. From derived thick target yields, optimal energy domain and batch yields for 68Ge production were calculated and contamination (from 69Ge and 71Ge) is discussed. A PC-controlled, automated dissolution and separation chemistry set-up for delivery of nca 69Ge was developed (yield about 90%) and implemented in an industrial system ready to be mounted in a hot cell. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The introduction of 68Ga-based positron emission tomography (PET) to clinical practice using 68Ge/68Ga generator represents a developmental milestone in the field of molecular imaging. Herein, we report a systematic study on 68Ga complexes with different bifunctional chelators (BFCs) and the effect of metal ion impurities on the radiochemical yields in order to identify the most suitable BFC to be used for the development of 68Ga-based target specific radiopharmaceuticals. Methods: Radiolabeling of four commonly used BFCs namely p-isothiocyanato benzyl derivatives of diethylenetriaminepentacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) with 68Ga was studied with respect to optimal radiolabeling conditions, effect of metal ion impurities on radiochemical yield, in vitro stability and in vivo clearance properties in biological system. Results: Out of the four BFCs studied, p-isothiocyanato benzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) could be radiolabeled instantly with 68Ga at room temperature with >98% yield, even in presence of up to 10ppm of other metal ion impurities (such as Zn, Cu, Fe, Al, Sn and Ti ions). The 68Ga-complex of NOTA-NCS demonstrated high in vitro stability even in the presence of 1000 times molar excess of metal ions (such as Fe, Cu, Zn and Ca ions). In contrast, other 68Ga-labeled BFCs (DTPA-NCS, DOTA-NCS and PCTA-NCS) showed reduced radiochemical yields when incubated with the above concentration of metal ions. The biodistribution studies in Swiss mice revealed that 68Ga-NOTA-NCS cleared rapidly through the kidneys with minimum retention in any major organ. Conclusions: The simple and rapid approach for preparation of 68Ga-radiopharmaceuticals using NOTA based bifunctional chelators would render 68Ga-radiopharmaceutical chemistry more convenient with minimum interference from other metal ion impurities; and increase the scope of making 68Ga based agents for PET imaging. [Copyright &y& Elsevier]

Abstract: Interest in using 68Ga is rapidly increasing for clinical PET applications due to its favorable imaging characteristics and increased accessibility. The focus of this study was to provide our long-term evaluations of the two TiO2-based 68Ge/68Ga generators and develop an optimized automation strategy to synthesize [68Ga]DOTATOC by using HEPES as a buffer system. This data will be useful in standardizing the evaluation of 68Ge/68Ga generators and automation strategies to comply with regulatory issues for clinical use. [Copyright &y& Elsevier]

Abstract: Radiolabeled benzamides have been reported to be attractive agents for targeting malignant melanoma as they bind melanin and display high accumulation in melanoma cells. Herein, we report the synthesis and bioevaluation of a novel 68Ga-labeled benzamide as a potential PET agent for malignant melanoma. The novel radiotracer was synthesized in good radiochemical yields (80% decay corrected yield) and high specific radioactivity (10GBq/μmol). Cellular uptake of 68Ga-SCN-NOTA-BZA was significantly higher in B16F10 cells (mouse melanoma) treated with L-tyrosine. Biodistribution and micro-PET studies of 68Ga-SCN-NOTA-BZA in B16F10-bearing mice showed selective uptake into the tumor. The radiotracer was cleared via renal excretion without further metabolism. These results demonstrate that 68Ga-SCN-NOTA-BZA is a potential PET probe for malignant melanoma. [Copyright &y& Elsevier]

A chromatographic 68Ge/68Ga generator using nano zirconia as the sorbent matrix was developed to avail 68Ga in an organic medium for industrial radiotracer applications. Acetylacetone was used as the eluent for the extractive desorption of 68Ga ions from the sorbent phase. The effect of varying the amount of acetylacetone on 68Ga yield and achieving ideal experimental conditions were studied. The major advantage of this generator is its ability to deliver ready to use “industrial 68Ga tracer” with > 90% yield and high radionuclidic and radiochemical purity. The performance of the generator remained consistent on repeated elutions over a period of 1 year. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Most of the commercially available 68Ge/68Ga generator systems are not optimally designed for direct applications in a clinical context. We have developed a nano-zirconia based 68Ge/68Ga generator system for accessing 68Ga amenable for the preparation of radiopharmaceuticals. Methods: Nano-zirconia was synthesized by the in situ reaction of zirconyl chloride with ammonium hydroxide in alkaline medium. The physical characteristics of the material were studied by various analytical techniques. A 740 MBq (20 mCi) 68Ge/68Ga generator was developed using this sorbent and its performance was evaluated for a period of 1 year. The suitability of 68Ga for labeling biomolecules was ascertained by labeling DOTA-TATE with 68Ga. Results: The material synthesized was nanocrystalline with average particle size of ∼7 nm, pore-size of ∼4 Å and a high surface area of 340±10 m2 g−1. 68Ga could be regularly eluted from this generator in 0.01N HCl medium with an overall radiochemical yield >80% and with high radionuclidic (<10−5% of 68Ge impurity) and chemical purity (<0.1 ppm of Zr, Fe and Mn ions). The compatibility of the product for preparation of 68Ga-labeled DOTA-TATE under the optimized reaction conditions was found to be satisfactory in terms of high labeling yields (>99%). The generator gave a consistent performance with respect to the elution yield and purity of 68Ga over a period of 1 year. Conclusions: The feasibility of preparing an efficient 68Ge/68Ga generator which can directly be used for biomedical applications has been demonstrated. [Copyright &y& Elsevier]

Abstract: Objectives: PET scintigraphy with 68Ga-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO2-based 68Ge/68Ga generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated. Methods: Characteristics of 4 SnO2-based generators (range 0.4–1GBq 68Ga in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO2-based 68Ge/68Ga generators were monitored, while [HCl] of the eluens was varied from 0.3–1.0M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the 68Ga eluate were performed using anion and cation exchange. Concentrated 68Ga eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. 68Ga-DOTA-TATE-containing solution was purified and RNP increased by SPE, therefore also 11 commercially available SPE columns were investigated. Results: The amount of elutable 68Ga activity varies when the concentration of the eluens, HCl, was varied, while 68Ge activity remains virtually constant. SnO2-based 68Ge/68Ga generator elutes at 0.6M HCl >100% of the 68Ga activity at calibration time and ±75% after 300 days. Eluate at discharge was sterile and Endotoxins were <0.5EU/mL, RNP was always <0.01%. Metal ions in the eluate were <10ppm (in total). Highest desorption for anion purification was obtained with the 30mg Oasis WAX column (>80%). Highest desorption for cation purification was obtained using a solution containing 90% acetone at increasing molarity of HCl, resulted in a 68Ga desorption of 68±8%. With all 68Ge/68Ga generators and for all 3 purification methods a SA up to 50MBq/nmol with >95% incorporation (ITLC) and RCP (radiochemical purity) by HPLC ±90% could be achieved. Purification and concentration of the eluate with anion exchange has the benefit of more elutable 68Ga with 1M HCl as eluens. The additional washing step of the anion column with NaCl and ethanol, resulted in a lower and less variable [H+] in the eluate, and, as a result the pH in the reaction vial is better controlled, more constant, and less addition of buffer is required and concordant smaller reaction volumes. Desorption of 68Ga-DOTA-TATE of SPE columns varied, highest desorption was obtained with Baker C18 100mg (84%). Purification of 68Ga-DOTA-TATE by SPE resulted in an RNP of <10−4%. Conclusions: Eluate of SnO2-based 68Ge/68Ga generator, either by fractionated elution as by ion exchange can be used for labelling DOTA-peptides with 68Ga at a SA of 50MBq/nmol at >95% incorporation and a RCP of ±90%. SPE columns are very effective to increase RNP. [Copyright &y& Elsevier]

Abstract: Introduction: Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of 68Ga-DOTATOC and PET/CT. Methods: In this work, a purification method for the 68Ge/68Ga generator eluate and a method to produce 68Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the 68Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and γ-ray spectrometry. Results: 68Ga-DOTATOC preparations (n=33) were carried out with a mean synthesis yield of 59.3±2.8% (not corrected for decay) and a batch activity ranging from 555 to 296 MBq. The radiochemical and radionuclidic purity were >98% and 99.9999%, respectively. With this purification process, >95% of the Fe(III), Zn(II) and Mn(II) were eliminated from the solution. Conclusions: 68Ga-DOTATOC produced with this method can be efficiently used in nuclear medicine departments for PET evaluations. [Copyright &y& Elsevier]

Abstract: Introduction: Generator-produced positron emission tomography tracers have gained much attention recently due to favorable imaging characteristics, accessibility and affordability. The focus of this study was to design and validate a semiautomated module for 68Ga-labeled chemistry utilizing infrared-based heating for rapid control of thermal cycle. Methods: A prototype module was built and installed in our laboratory. DOTA (1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetra-acetic acid) was manually labeled (10–1000 nmol) with 68Ga to optimize synthesis conditions. For automation, 250 nmol of DOTA was labeled with 68Ga with reaction times of 5 min (n=5), 10 min (n=5) and 20 min (n=6). A dose calibrator and radio-thin-layer chromatography were used to access the product yield and quality of both manual and automated syntheses. Results: A semiautomated 68Ga synthesis module was developed. The system showed that software control could be used to drive a multistep radiochemical synthesis and to produce 68Ga-DOTA with >95% radiochemical purity, similar to that in manual synthesis. The device also showed that for a short reaction time of 5 min, decay-corrected radioactive yields of >70% could be achieved. The total synthesis was as short as 22 min, including 6–8 min for HCl evaporation. The temperature and pressure profiles of the process were consistent. Conclusion: We demonstrated the use of a commercially available 68Ga/68Ge generator with a semiautomated module to successfully label the bifunctional chelator DOTA with 68Ga. Further investigation with different 68Ga-labeled bioconjugates is warranted to demonstrate the usefulness of the module as a tool for tracer development and imaging research. [Copyright &y& Elsevier]

68Ge/68Ga generators provide cyclotron-independent access to positron emission tomography (PET) radiopharmaceuticals. We describe a system which allows the safe and efficient handling of 68Ge/68Ga generator eluates for labelling of DOTA-derivatised peptide ligands. The system comprises concentration and purification of the 68Ga eluate as well as labelling and purification steps for peptides, and can be used with different 68Ge/68Ga generator types. The suitability and efficiency were tested with two different DOTA-derivatised somatostatin derivatives and a DOTA-derivatised bombesin derivative. Amounts of 10–20 nmol of the peptides were sufficient and resulted in labelling yields of 50% for all peptides. The built-in safety precautions have proven to be appropriate in allowing use of the method for routine clinical applications. The system was set up and operated in a “hot lab” by personnel with no previous experience in the preparation of PET radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8, Met(O2)11]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO2 generator matrix as well as preliminary results on the adaptability to produce [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi8, Met(O2)11]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP mixed with [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP. [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP providing sufficient activity for 1–2 human doses. The resultant formulation of [68Ga]Ga-/[213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi8, Met(O2)11]SP—a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP and [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities. [ABSTRACT FROM AUTHOR]

We report column material for a 68Ge/68Ga generator with acid resistance and excellent adsorption and desorption capacity of 68Ge and 68Ga, respectively. Despite being a core element of the 68Ge/68Ga generator system, research on this has been insufficient. Therefore, we synthesized a low molecular chitosan-based TiO2 (LC-TiO2) adsorbent via a physical trapping method as a durable 68Ge/68Ga generator column material. The adsorption/desorption studies exhibited a higher separation factor of 68Ge/68Ga in the concentration range of HCl examined (0.01 M to 1.0 M). The prepared LC-TiO2 adsorbent showed acid resistance capabilities with >93% of 68Ga elution yield and 1.6 × 10−4% of 68Ge breakthrough. In particular, the labeling efficiency of DOTA and NOTA, by using the generator eluted 68Ga, was quite encouraging and confirmed to be 99.65 and 99.69%, respectively. Accordingly, the resulting behavior of LC-TiO2 towards 68Ge/68Ga adsorption/desorption capacity and stability with aqueous HCl exhibited a high potential for ion-exchange solid-phase extraction for the 68Ge/68Ga generator column material. [ABSTRACT FROM AUTHOR]

The neurotensin is a tridecapeptide involved in the proliferation of colon cancer, the overexpression of neurotensin receptors occurring at an early stage development of many tumours. Targeting neurotensin receptors by using the same biological active molecule is an effective approach for both imaging quantification and treatment. The present work aimed to demonstrate the ability of radiolabelled neurotensin to specifically target colon cancer cells, and substantiate its usefulness in targeted imaging and radiotherapy, depending on the emission of the coupled radioisotope. Syntheses of 68Ga–DOTA–NT and 177Lu–DOTA–NT were developed to obtain a level of quality suitable for preclinical use with consistent high synthesis yields. Radiochemical purity meets the pharmaceutical requirements, and it is maintained 4 h for 68Ga–DOTA–NT and 48 h for 177Lu–DOTA–NT. Extensive in vitro studies were conducted to assess the uptake and retention of 68Ga–DOTA–NT, the amount of non-specific binding of neurotensin and the effect of 177Lu–DOTA–NT on HT–29 cells. In vivo biodistribution of 68Ga–DOTA–NT revealed significant uptake at the tumour site, along with fast clearance evidenced by decreasing activity in kidneys and blood after 60 min p.i. 177Lu–DOTA–NT exhibited similar uptake in the tumour, but also a significant uptake at 14 days p.i. in the bone marrow was reported. These results successfully demonstrated the potential of neurotensin to deliver imaging/therapeutic 68Ga/177Lu radioisotopes pair, but also the need for further evaluation of the possible radiotoxicity effects on the liver, kidneys or bone marrow. [ABSTRACT FROM AUTHOR]

Quality of the 68 Ga solution eluted from a 68 Ge/ 68 Ga generator (Galli Eo ® ) was evaluated. Elution was performed 488 times from 21 to 484 days (ca. 15 months) after the calibration date. The eluted 68 Ga activity was 329 MBq to 1,148 MBq, which decreased with the decay of 68 Ge, but no significant change was observed in the elution yields (62.8±2.2%). The half-life of the eluted radioactivity was 67.8±0.1 min, the radionuclide purity of 68 Ga was ≥99.9%, the 68 Ge breakthrough was 0.000024 ±0.000004%, and the radiochemical purity of 68 Ga 3+ was 99.7±0.2%. Fe and Zn were detected as metal impurities in the eluent, but both were ≤10 μg/GBq. The endotoxin concentration of the eluate was ≤5 EU/mL, and the eluent passed the sterility test. These results show that the generator can stably provide 68 Ga solution over a 15-month period.