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The radiometal gallium-68 (Ga-68) has garnered significant interest due to its convenient production via compact and widely available generators and the high performance of 68Ga-labeled compounds for positron-emission tomography (PET) imaging for cancer diagnosis and management of patients undergoing targeted radionuclide therapy. Given the short half life of Ga-68 (68 min), microfluidic-based radiosynthesis is a promising avenue to establish very rapid, efficient, and routine radiolabeling with Ga-68; however, the typical elution volume of Ga-68 from a generator (4-10 mL) is incompatible with the microliter reaction volumes of microfluidic devices. To bridge this gap, we developed a microscale cartridge-based approach to concentrate Ga-68. By optimizing cartridge design, resin type, resin mass, and eluent composition, Ga-68 was reliably concentrated from ~6 mL to ~80 µL with high recovery efficiency (>97%, n = 14). Furthermore, this method is suitable for both single- and dual-generator setups. To demonstrate suitability of the concentrated radiometal for radiolabeling, we performed microdroplet synthesis of [68Ga]Ga-PSMA-11, achieving high radiochemical yield (83 ± 11%, n = 3), excellent radiochemical purity (>99%), and high apparent specific activity (255-320 MBq/μg). The entire process, including Ga-68 concentration, radiosynthesis, purification, and formulation, was completed in 12 min. Starting with activity of 0.81-0.84 GBq, 0.51-0.64 GBq of product was produced, sufficient for multiple patient doses. This work paves the way to clinical-scale production of other 68Ga-labeled compounds using droplet microreactor methods, or high-throughput labeling optimization or compound screening of 68Ga-labeled probes using droplet reaction arrays.

The radiometal gallium-68 (Ga-68) has garnered significant interest due to its convenient production via compact and widely available generators and the high performance of 68Ga-labeled compounds for positron-emission tomography (PET) imaging for cancer diagnosis and management of patients undergoing targeted radionuclide therapy. Given the short half life of Ga-68 (68 min), microfluidic-based radiosynthesis is a promising avenue to establish very rapid, efficient, and routine radiolabeling with Ga-68; however, the typical elution volume of Ga-68 from a generator (4–10 mL) is incompatible with the microliter reaction volumes of microfluidic devices. To bridge this gap, we developed a microscale cartridge-based approach to concentrate Ga-68. By optimizing cartridge design, resin type, resin mass, and eluent composition, Ga-68 was reliably concentrated from ~6 mL to ~80 µL with high recovery efficiency (>97%, n = 14). Furthermore, this method is suitable for both single- and dual-generator setups. To demonstrate suitability of the concentrated radiometal for radiolabeling, we performed microdroplet synthesis of [68Ga]Ga-PSMA-11, achieving high radiochemical yield (83 ± 11%, n = 3), excellent radiochemical purity (>99%), and high apparent specific activity (255–320 MBq/μg). The entire process, including Ga-68 concentration, radiosynthesis, purification, and formulation, was completed in 12 min. Starting with activity of 0.81–0.84 GBq, 0.51–0.64 GBq of product was produced, sufficient for multiple patient doses. This work paves the way to clinical-scale production of other 68Ga-labeled compounds using droplet microreactor methods, or high-throughput labeling optimization or compound screening of 68Ga-labeled probes using droplet reaction arrays. [ABSTRACT FROM AUTHOR]

The radiometal gallium-68 (Ga-68) has garnered significant interest due to its convenient production via compact and widely available generators and the high performance of 68Ga-labeled compounds for positron-emission tomography (PET) imaging for cancer diagnosis and management of patients undergoing targeted radionuclide therapy. Given the short half life of Ga-68 (68 min), microfluidic-based radiosynthesis is a promising avenue to establish very rapid, efficient, and routine radiolabeling with Ga-68; however, the typical elution volume of Ga-68 from a generator (4–10 mL) is incompatible with the microliter reaction volumes of microfluidic devices. To bridge this gap, we developed a microscale cartridge-based approach to concentrate Ga-68. By optimizing cartridge design, resin type, resin mass, and eluent composition, Ga-68 was reliably concentrated from ~6 mL to ~80 µL with high recovery efficiency (>97%, n = 14). Furthermore, this method is suitable for both single- and dual-generator setups. To demonstrate suitability of the concentrated radiometal for radiolabeling, we performed microdroplet synthesis of [68Ga]Ga-PSMA-11, achieving high radiochemical yield (83 ± 11%, n = 3), excellent radiochemical purity (>99%), and high apparent specific activity (255–320 MBq/μg). The entire process, including Ga-68 concentration, radiosynthesis, purification, and formulation, was completed in 12 min. Starting with activity of 0.81–0.84 GBq, 0.51–0.64 GBq of product was produced, sufficient for multiple patient doses. This work paves the way to clinical-scale production of other 68Ga-labeled compounds using droplet microreactor methods, or high-throughput labeling optimization or compound screening of 68Ga-labeled probes using droplet reaction arrays.

Purpose: The purpose of these studies was to develop a nerve growth factor (NGF) radiometal-chelator conjugate to determine the biodistribution and brain uptake of NGF by positron emission tomography/computerized tomography (PET-CT). Procedures. Purified NGF from llama seminal plasma was conjugated with FITC, and the chelator NOTA or DFO. NGF conjugates were evaluated for bioactivity. NOTA- and DFO-conjugated NGF were radiolabeled with gallium-68 or zirconium-89 ([68 Ga]GaCl3, half-life = 68 min; [89Zr]Zr(oxalate)4, half-life = 3.3 days). [89Zr]Zr-NGF was evaluated for biodistribution (0.5, 1, or 24 h), PET imaging (60 min), and brain autoradiography in mice. Results: Cell-based in vitro assays confirmed that the NGF conjugates maintained NGF receptor-binding and biological activity. Zirconium-89 and gallium-68 radiolabeling showed a high efficiency; however, only[89Zr]Zr-NGF was stable in vitro. Biodistribution studies showed that, as with most small proteins < 70 kDa, [89Zr]Zr-NGF uptake was predominantly in the kidney and was cleared rapidly with almost complete elimination of NGF at 24 h. Dynamic PET imaging from 0–60 min showed a similar pattern to ex vivo biodistribution with some transient liver uptake. Interestingly, although absolute brain uptake was very low, at 24 h after treatment, cerebral cortex uptake was higher than any other brain area examined and blood. Conclusions: We conclude that conjugation of DFO to NGF through a thiourea linkage allows effective radiolabeling with zirconium-89 while maintaining NGF bioactivity. Following intravenous administration, the radiolabeled NGF targets non-neuronal tissues (e.g., kidney, liver), and although absolute brain uptake was very low, the brain uptake that was observed was restricted to the cortex. [ABSTRACT FROM AUTHOR]

Abstract The aluminium-[18F]fluoride ([18F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [18F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [18F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method.

Radiosynthesis of a novel bifunctional chelator for gallium-68 (Ga-68) chelation has been fabricated through peptide synthesis. Using of solid phase peptide synthesizer, linear structure of three repeating unit of glutamic acid was primarily generated. Protecting group of tert-butyl in intermediate was then cleaved and eventually yield as tri-γ-glutamic acid polypeptide (tri-γ-GAP). Mass spectrometry revealed m/z was 406.1378 that well corresponded with proposed structure of three repeating unit of glutamic acids. To label Ga-68 with synthesized tri-γ-GAP, the elution of 68GaCl3 was chelated to tri-γ-GAP with high temperature condition. It was subsequently purified through Sep-Pak C18 cartridge. Radio thin-layer chromatography demonstrated that the labeling efficiency of 68Ga-tri-γ-GAP was 3.5-3.8 mCi with radiochemical purity more than 98%. The pH was 4.5-5.0. Conclusively, synthesized tri-γ-GAP comprising three N-dentate and four OH-dentate. One more free OH-dentate of tri-γ-GAP provided more applicability over universal chelator of (N,N',N"-1,4,7,-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) on Ga-68 labeling. It is able to link with pharmacological substances without any further modification whereas NOTA needs to be synthesized a specific linker for an attaching with bioactive pharmacological molecule. Novel small peptide chelator of tri-γ-GAP is a promising molecule for Ga-68 labeling with versatile application in radiopharmaceutical diagnosis. [ABSTRACT FROM AUTHOR]

The aluminium-[18F]fluoride ([18F]AlF) radiolabelling method combines the favourable decay characteristics of fluorine-18 with the convenience and familiarity of metal-based radiochemistry and has been used to parallel gallium-68 radiopharmaceutical developments. As such, the [18F]AlF method is popular and widely implemented in the development of radiopharmaceuticals for the clinic. In this review, we capture the current status of [18F]AlF-based technology and reflect upon its impact on nuclear medicine, as well as offering our perspective on what the future holds for this unique radiolabelling method. [ABSTRACT FROM AUTHOR]

Cyclotron-produced radiometals must be separated from the irradiated target and purified from other metal impurities, which could interfere with the radiolabeling process. We compared different chromatographic and colorimetric methods to determine the amount of transition metals in radioactive samples. Besides commercially available colorimetric tests, 4-(2-pyridylazo)resorcinol and xylenol orange were used as a non-selective metal reagents, forming water-soluble chelates with most of the transition metals immediately. We compared the applicability of pre- and post-column derivatization, as well as colorimetric determination without separation. The studied chromatographic and colorimetric analyses are not suitable to completely replace atomic spectroscopic techniques for the determination of metal contaminants in radioactive samples, but they may play an important role in the development of methods for the purification of radiometals and in their routine quality control.

Diagnostic and therapeutic nuclear medicine relies heavily on radiometal nuclides. The most widely used and well-known radionuclide is technetium-99m (99mTc), which has dominated diagnostic nuclear medicine since the advent of the 99Mo/99mTc generator in the 1960s. Since that time, many more radiometals have been developed and incorporated into potential radiopharmaceuticals. One critical aspect of radiometal-containing radiopharmaceuticals is their stability under in vivo conditions. The chelator that is coordinated to the radiometal is a key factor in determining radiometal complex stability. The chelators that have shown the most promise and are under investigation in the development of diagnostic and therapeutic radiopharmaceuticals over the last 5 years are discussed in this review. [ABSTRACT FROM AUTHOR]

Magnetic Fe3O4 nanoparticles with narrow size distribution were synthesized by simple and high yielded co-precipitation technique using ferrous salts with a molar ratio of Fe3+/Fe2+=2. After coating of the nanoparticles with Stöber silica (SiO2@Fe3O4), nanoparticles were functionalized by amine groups. Then chelator molecules diethylenetriaminepentaacetic (DTPA) and tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were coupled to the APTS-SiO2@Fe3O4 to chelating Y-90 radiometal that makes these nanoparticles a suitable agent for therapeutic application as dual-modality PET/MRI imaging. The results show the coupling of DTPA takes place better than DOTA. Synthesis of magnetic nanoparticles (MNPs) was followed by structure identification using XRD, SEM, TGA and IR techniques. In order to trace MNPs biodistribution, the radiolabeled MNPs-DTPA were prepared using 90Y (production of 90Y/90Sr generator) with a good labeling efficiency (about 92%, RTLS method). The biodistribution of the radiolabeled MNPs was checked in normal male rats up to 24 h compared to free Y3+. The data shows that the tracer accumulation is in reticuloendothelial tissue while the stability of the complex is highly retained. [ABSTRACT FROM AUTHOR]

In this study, magnetic multimodal nanoparticles with potential applications in magnetic- and nuclear-medicine imaging, magnetic resonance imaging, hyperthermia, and theranostic (therapeutic and diagnostic), applications were prepared by coating iron oxide nanoparticles with silica (core-shell), functionalizing with aminopropyltriethoxy silane and coupling with diethylenetriamine pentaacetic acid ligand (DTPA). Radiolabeling of core-shell-DTPA particles with 68Ga radiometal was carried out through chelation of 68Ga(III) ions by DTPA and was used for positron emission tomography. The biodistribution of the 68Ga-radiolabeled magnetic nanoparticles compared to free 68Ga(III) was checked in normal Balb/c mice up to 2 h. [ABSTRACT FROM AUTHOR]

Scandium-43 is an emerging PET radiometal that was produced by α-particle bombardment on natural CaCO 3 target via natCa (α,p) 43Sc and natCa (α,n) 43Ti→43Sc reactions using K-130 cyclotron at VECC. A robust radiochemical procedure based on selective precipitation of 43Sc as Sc(OH) 3 was developed for separation of the radioisotope from the irradiated target. The overall yield of the separation process was >85% and it was obtained in a form suitable for preparation of target specific radiopharmaceuticals for PET imaging of cancer. • 43Sc was produced via natCa(α,p)43Sc and natCa(α,n)43Ti.→43Sc reactions in a cyclotron. • A selective precipitation-based process was developed for isolation of 43Sc from Ca. • 43Sc was found suitable for preparation of radiopharmaceuticals with high yield. [ABSTRACT FROM AUTHOR]

We present the production of 58mCo on a small, 13 MeV medical cyclotron utilizing a siphon style liquid target system. Different concentrated iron(III)-nitrate solutions of natural isotopic distribution were irradiated at varying initial pressures and subsequently separated by solid phase extraction chromatography. The radio cobalt (58m/gCo and 56Co) was successfully produced with saturation activities of (0.35 ± 0.03) MBq μA−1 for 58mCo with a separation recovery of (75 ± 2) % of cobalt after one separation step utilizing LN-resin. • First production of 58mCo in a liquid target on a medical cyclotron. • Saturation activity 0.35 ± 0.03 MBq/μA. • Separation recovery of Co of 75 ± 2%. [ABSTRACT FROM AUTHOR]

Radiolabeled diprenorphine (DPN) and analogs are widely used ligands for non-invasive brain imaging of opioid receptors. To develop complementary radioligands optimized for studies of the peripheral opioid receptors, we prepared a pair of hydrophilic DPN derivatives, conjugated to the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), for complexation with trivalent metals. The non-radioactive indium (III) complexes, tethered to the C6-oxygen position of the DPN scaffold by 6- to 9-atom spacers, displayed high affinities for binding to μ, δ and κ opioid receptors in vitro. Use of the 9-atom linker conferred picomolar affinities equipotent to those of the parent ligand DPN. The [ 111 In]-labeled complexes were prepared in good yield (>70%), with high radiochemical purity (∼99%) and high specific radioactivity (>4000 mCi/μmol). Their log D 7.4 values were –2.21 to –1.66. In comparison, DPN is lipophilic, with a log D 7.4 of +2.25. Further study in vivo is warranted to assess the suitability of these [ 111 In]-labeled DPN-DOTA conjugates for imaging trials. [ABSTRACT FROM AUTHOR]

The geldanamycin derivative 17-allylamino-?17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled 211At-ABY-025 and radiometal-labelled 111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer a emitter 211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells. [ABSTRACT FROM AUTHOR]

Objectives To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H 4 octapa with the therapeutic radiometal 90 Y. Methods The bifunctional chelators p -SCN-Bn-H 4 octapa and p -SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with 90 Y to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer. Results High radiochemical yields (>95%) were obtained with 90 Y-CHX-A″-DTPA-trastuzumab and 90 Y-octapa-trastuzumab after 15 min at room temperature. Both 90 Y-CHX-A″-DTPA-trastuzumab and 90 Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3 ± 4.0 %ID/g for 90 Y-CHX-A″-DTPA-trastuzumab and 30.1 ± 7.4 %ID/g for 90 Y-octapa-trastuzumab at 72 h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, 90 Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that 90 Y-CHX-A″-DTPA-trastuzumab and 90 Y-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls. Conclusions Ultimately, this work demonstrates that the acyclic chelators CHX-A″-DTPA and H 4 octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring 90 Y. [ABSTRACT FROM AUTHOR]

Introduction Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of 89 Zr, 68 Ga and for the first time 86 Y are discussed. Methods Aqueous solutions containing 1.35–1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. Results We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, 89 Zr (A sat = 360 MBq/μA and yield = 3.17 MBq/μA), 86 Y (A sat = 31 MBq/μA and yield = 1.44 MBq/μA), and 68 Ga (A sat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. 68 Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, 68 Ga and 86 Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate 89 Zr. [ABSTRACT FROM AUTHOR]

The production of positron-emitting isotopes of manganese is potentially important for developing contrast agents for dual-modality positron emission tomography and magnetic resonance (PET/MR) imaging, as well as for in vivo imaging of the biodistribution and toxicity of manganese. The decay properties of 52 Mn make it an excellent candidate for these applications, and it can easily be produced by bombardment of a chromium target with protons or deuterons from a low-energy biomedical cyclotron. Several parameters that are essential to this mode of production—target thickness, beam energy, beam current, and bombardment time—depend heavily on the availability of reliable, reproducible cross-section data. This work contributes to the routine production of 52g Mn for biomedical research by contributing experimental cross-sections for natural chromium ( nat Cr) targets for the nat Cr( p , x ) 52g Mn reaction, as well as for the production of the radiocontaminants 52m,54 Mn. [ABSTRACT FROM AUTHOR]

Significant interest in 44 Sc as a radioactive synthon to label small molecules for positron emission tomography (PET) imaging has been recently observed. Despite the efforts of several research groups, the ideal 44 Sc production and separation method remains elusive. Herein, we propose a novel separation method to obtain 44 Sc from the proton irradiation of calcium targets based on extraction chromatography, which promises to greatly simplify current production methodologies. Using the commercially available Uranium and Tetravalent Actinides (UTEVA) extraction resin we were able to rapidly (<20 min) recover >80% of the activity generated at end of bombardment (EoB) in small ~1 M HCl fractions (400 μL). The chemical purity of the 44 Sc eluates was evaluated through chelation with DOTA and DTPA, and by trace metal analysis using microwave induced plasma atomic emission spectrometry. The distribution coefficients ( K d ) of Sc(III) and Ca(II) in UTEVA were determined in HCl medium in a range of concentrations from zero to 12.1 M. The 44 Sc obtained with our method proved to be suitable for the direct labeling of small biomolecules for PET imaging, with excellent specific activities and radiochemical purity. [ABSTRACT FROM AUTHOR]

Introduction: Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of 44Sc (t1/2 =3.97h, Eavg,β + =1.47MeV, branching ratio=94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Methods: Solutions containing a high concentration (1.44–1.55g/mL) of natural-abundance calcium nitrate tetrahydrate (Ca(NO3)2 ·4 H2O) were irradiated on a 13MeV proton-beam cyclotron using a standard liquid target. 44gSc was produced via the 44Ca(p,n)44gSc reaction. Results: 44gSc was produced for the first time in a solution target with yields sufficient for early radiochemical studies. Saturation yields of up to 4.6±0.3MBq/μA were achieved using 7.6±0.3μA proton beams for 60.0±0.2minutes (number of runs n=3). Experimental data and calculation results are in fair agreement. Scandium was isolated from the target mixture via solid-phase extraction with 88±6% (n=5) efficiency and successfully used for radiolabelling experiments. The demonstration of the production of 44Sc in a liquid target greatly improves its availability for tracer development. [ABSTRACT FROM AUTHOR]

Cyclotron-produced radiometals must be separated from the irradiated target and purified from other metal impurities, which could interfere with the radiolabeling process. We compared different chromatographic and colorimetric methods to determine the amount of transition metals in radioactive samples. Besides commercially available colorimetric tests, 4-(2-pyridylazo)resorcinol and xylenol orange were used as a non-selective metal reagents, forming water-soluble chelates with most of the transition metals immediately. We compared the applicability of pre- and post-column derivatization, as well as colorimetric determination without separation. The studied chromatographic and colorimetric analyses are not suitable to completely replace atomic spectroscopic techniques for the determination of metal contaminants in radioactive samples, but they may play an important role in the development of methods for the purification of radiometals and in their routine quality control. [ABSTRACT FROM AUTHOR]

Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

In order to use new and promising radiometals for molecular imaging, it is important that they can be obtained as inexpensively and easily as possible. This often requires a cyclotron with solid target hardware or a radionuclide generator, which are not widely available for rarely used radionuclides. Here, we investigate the improved production of 44Sc with a siphon-style liquid target system and compare to our previous work with a simple liquid target. A metal salt solution with a high concentration of natural abundance Ca(NO 3) 2 (0.14 g/cm3) was irradiated with a medical cyclotron (12 MeV protons; 20 μA). 44Sc was produced via the natCa(p,x)44Sc reaction. As the pressure increase during irradiation was reduced in the siphon-style target, it was possible to irradiate with a higher proton beam current (20 μA) than with the simple liquid target system (7.9 μA). In addition, the saturation yield per μA of 44Sc was increased by a factor of 3.18 ± 0.05 (6.2 ± 0.1 MBq/μA with the siphon target versus 1.94 ± 0.08 MBq/μA with the simple target). This results in an overall increase in 44Sc activity by a factor of 11. • Production of Sc-44 in a siphon-style liquid target. • Increase in proton beam current on target by a factor of 2.5 over the simple target. • Increase in yield over a simple target by a factor of 11.03 • Increase in saturation yield per uA of beam current over a simple target by a factor of 3.18 [ABSTRACT FROM AUTHOR]

Scandium radioisotopes are increasingly considered viable radiolabels for targeted molecular imaging (Sc-43, Sc-44) and therapy (Sc-47). Significant technological advances have increased the quantity and quality of available radioscandium in the past decade, motivated in part by the chemical similarity of scandium to therapeutic radionuclides like Lu-177. The production and radiochemical isolation techniques applied to scandium radioisotopes are reviewed, focusing on charged particle and electron linac initiated reactions and using calcium and titanium as starting materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Systemic administration of lysine to mice injected with indium-111-labelled Fab fragment of a monoclonal antibody has been shown to reduce renal uptake/retention of the radiometal. This treatment should be applicable to clinical immunoscintigraphy and radioimmunotherapy with radiometal-labelled antibody fragments. [ABSTRACT FROM AUTHOR]