• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.11-17
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• 2019

Recently, antibody-like scaffold proteins have received a great deal of interest in diagnosis and therapy applications because of their intrinsic features that are often required for tumor imaging and therapy. Intrinsic issues that are associated with therapeutic application of antibody-like scaffold proteins, particularly in cancer treatment, include an efficient and straightforward radiolabeling for understanding in vivo biodistribution and excretion route, and monitoring therapeutic responses. Herein, we report an efficient and straightforward method for radiolabeling of antibody-like scaffold proteins with the $[^{99m}Tc(OH_2)_3(CO)_3]^+$ ($^{99m}Tc$-tricarbonyl) by using a site-specific direct labeling method via hexahistidine-tag, which is a widely used for general purification of recombinant proteins with His-affinity chromatography. Repebody is a new class of antibody-like scaffold protein that consists of highly diverse leucine-rich repeat (LRR) modules. Although all possible biomedical applications with repebody are ongoing, it's in vivo biodistribution and excretion pathway has not yet been explored. In this study, hexahistidine ($His_6$)-tag bearing repebody (rEgH9) was labeled with [$^{99m}Tc$]-tricarbonyl. Repebody protein was radiolabeled with high radiolabeling efficiency (>90%) and radiolabeled compound was more than 99% pure after purification. These results clearly demonstrate that the present radiolabeling method will be useful molecular imaging study.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.45-50
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• 2018

Great efforts are currently devoted to the development of new approaches for the labeling of cells using appropriate radionuclides. While fluoride-18 and copper-64 have been extensively studied as short-term and intermediate-term trafficking agents, iodide was studied less intensely. Here, we report a new cell labeling agent labeled with $^{131}I$, $[^{131}I]$oleyl-4-iodobenzoate ($[^{131}I]$OIB) for long-term cell trafficking. A precursor of $[^{131}I]$OIB was obtained in two steps, with the yield of 35%. The radiochemical yield of $[^{131}I]$OIB was over 50%. While $[^{131}I]$OIB could label different cells, L6 cells showed the highest cell-labeling efficiency. The $[^{131}I]$OIB-labeled L6 cells were imprinted into a rat heart, and then monitored noninvasively for 2 weeks by gamma camera imaging. We conclude that $[^{131}I]$OIB is a good candidate molecule for a long-term cell trafficking agent.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.23-33
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• 2023

Prostate cancer ranks as the world's second most frequently diagnosed cancer among men, and is responsible for the fifth highest number of cancer-related deaths in this population. The development of effective diagnostic and therapeutic approaches for prostate cancer remains a major challenge in the field of oncology. Over the past few years, the prostate-specific membrane antigen (PSMA) has raised as a hopeful tracer for the diagnosis and treatment of prostate cancer.Various radioisotopes, such as ¹³¹I, ^99mTc, ⁶⁸Ga, and ¹⁷⁷Lu, have been used to label PSMA analogues, with varying degrees of success. Among these, ⁶⁸Ga-PSMA-11 and ¹⁷⁷Lu-PSMA-617 have emerged as the most promising radioligands for clinical use. Recently, researchers have been exploring the use of other radioisotopes, such as ²¹¹At, ⁸⁹Zr, ^64/67Cu, and ^203/212Pb, for the labeling of PSMA-targeted radioligands. These radioisotopes have unique properties that may offer advantages over existing radioligands, such as longer half-lives, higher specific activities, and different emission profiles. Efforts are currently underway to develop these radiopharmaceuticals and make them more widely available for clinical use. These exciting developments highlight the potential of PSMA-targeted radioligands for the diagnosis and treatment of prostate cancer, and provided significant implications for the management of this disease in the future. The current study aims to provide a comprehensive summary of the latest research and clinical applications of radiolabeled PSMA inhibitors for diagnoses and therapy of prostate cancer, emphasizing the exciting developments in the field and their potential impact on clinical practice.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.71-76
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• 2022

Indigenous diagnostic dose of ¹³¹I-labeled meta-iodobenzylguanidine ([¹³¹I]mIBG) was prepared via Cu⁺ catalyzed isotope exchange reaction generated in situ by sodium metabisulfite for imaging of neuroblastoma tumor. [¹³¹I]mIBG was produced in overall 85-90% radiochemical yield. The average amount of radioactivity of [¹³¹I]mIBG was 2164 MBq (1998-2331MBq) with an average specific activity > 1000 MBq/mg at the end of synthesis. The radiochemical purity was ≥ 99.9% after purification through Dowex-1 × 8 ion exchange resin (100-150 mesh) at the date of preparation. The stability of [¹³¹I]mIBG at concentration 480-555 MBq/mL was > 97% at 4 ℃ after 4 days. The room temperature (25 ℃) stability of [¹³¹I]mIBG was > 98% after 24 h. Biodistribution of [¹³¹I]mIBG in patient showed uptake in salivary glands, liver, spleen and excreted though urinary bladder. Neuroendocrine medicated uptake into tumor lesion and metastatic sites were noted which strongly correlate with the morphological abnormalities of patient.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.77-85
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• 2022

The Td05 and Sgc8c, DNA-based aptamers, are well-known to target internalized surface markers (IGHM and PTK7) of Burkitt's lymphoma and acute lymphoblastic leukemia (ALL). Thus, Td05 and Sgc8c labeled with metallic radioisotope ⁶⁴Cu can be evaluated as potential diagnostic PET imaging agents. In this study, we modified the carbon chain length of the last adenosine of aptamer (n = 3, 6, 12) to increase tumor cell uptake and select the best candidate among six types of aptamer analogues and one adenosine of aptamer. After labeling of ⁶⁴Cu, [⁶⁴Cu]Cu-DOTA-aptamer analogues were evaluated in vitro studies (serum stability, Log P values, cell uptake, biodistribution). Then, we evaluate in vivo PET imaging study for two candidates (⁶⁴Cu-DOTA-C12-Sgc8c, ⁶⁴Cu-DOTA-C6-Td05). PET images clearly visualize tumors at 24 h post-injection rather than at an early time point and the tumor-to-background ratio also increases at the delay time point. ⁶⁴Cu-DOTA-C12-Sgc8c and ⁶⁴Cu-DOTA-C6-Td05 could be used as potential radiotracers for lymphoma.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.2
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• pp.102-115
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• 2020

In the state of Positronium (Ps), which is an unstable material created by the temporary combination of electrons and positrons, the imaging technology through photo-conversion methodology is emerging as a new research theme under resonance conditions through terahertz electromagnetic waves. Normally, Positronium can be observed in the positron emission computed tomography (PET) process when an unstable, separate state that remains after the pair annihilation of an electron and a positron remains. In this study, terahertz (THz) waves and Cherenkov radiation (CR) are generated using the principle of ponderomotive force in the plasma wake-field acceleration, and electrons and positrons are simultaneously generated by using a relativistic electron beam without using a PET device. We confirm the possibility of Positronium photoconversion technology in terahertz electromagnetic resonance conditions through experimental studies that generate an unstable state. Here, a relativistic electron beam (REB) energy of 0.5 MeV (γ=2) was used, and the terahertz wave frequencies is G-band. Meanwhile, a THz wave mode converting three-stepped axicon lens was used to apply the photoconversion technology. Through this, light emission in the form of a luminescence-converted Bessel beam can be verified. In the future, it can be used complementarily with PET in nuclear medicine in the field of medical imaging.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.85-90
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• 2017

$^{68}Ga-PET$ is of growing importance in the practice of nuclear medicine diagnostic imaging for neuroendocrine tumors as well as prostate cancers. Following this interests, we herein present the radiosynthesis process of [$^{68}Ga$]edotreotide ([$^{68}Ga$]DOTA-TOC) based on the fully automated procedure for clinical doses that can be provided the reduction of radiation exposure and high reproducibility. The quality controls of clinical doses in compliant with European Pharmacopoeia are also discussed.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.91-97
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• 2017

$^{18}F-THK-5351$ is a PET radiotracer to image the hyperphosphorylated tau fibrillar aggregates in human brain. This protocol describes the optimized radiosynthesis of $^{18}F-THK-5351$ using a commercial GE $TRACERlab^{TM}$ $FX_{FN}$ radiosynthesis module. $^{18}F-THK-5351$ was prepared by nucleophilic [$^{18}F$]fluorination from its protected tosylate precursors, (S)-(2-(2-methylaminopyrid-5-yl)-6-[[2-(tetrahydro-2H-pyran-2-yloxy)-3-tosyloxy]propoxy] quinolone(THK-5352), at $110^{\circ}C$ for 10 min in dimethyl sulfoxide, followed by deprotection with 1 N HCl. The average radiochemical yield of $^{18}F-THK-5351$ was $31.9{\pm}6.7%$(decay-corrected, n = 10), with molar activity of $198.1{\pm}33.9GBq/{\mu}mol$($5.4{\pm}0.9Ci/{\mu}mol$, n = 10). The radiochemical purity was determined to be above 98%. The overall production time including HPLC purification is approximately 70 min. This fully-automated protocol is validated for clinical use.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.145-151
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• 2019

Fluorine-18 is considered to be the radionuclide of choice for positron emission tomography (PET). Thus, the development of small molecule-based radiopharmaceuticals for use in diagnostic imaging relies heavily on efficient radiofluorination techniques. Until the early 2000s, diaryliodonium salts and aryliodonium ylides were widely employed as labeling precursors to yield aromatic PET radiotracers with cyclotron-produced [¹⁸F]fluoride ion. Rapid recent progress in the development of efficient borylation methods has led to a paradigm shift in ¹⁸F-labeling methods. In addition, deoxyfluorination has attracted a great deal of interest as an alternative approach to aryl ring activation with ¹⁸F^-. In this review, methods for radiolabel development are discussed with a specific focus on the progress made in the last 5 years. Other interesting ¹⁸F-based protocols are also briefly introduced. New methods for exploiting ¹⁸F^- are expected to increase the number of ¹⁸F-labeling methods, to allow applications in a range of chemical environments.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.27-38
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• 2020

Alzheimer's disease (AD) is one of the challenging conditions that have no cure, yet early diagnosis can help to control the disease. PET imaging of tau has several advantages, such as being a noninvasive, safe diagnostic technique that correlates directly with the disease progression. Many tau tracers have been reported to date; however, the chemical scaffolds of them fall in a narrow chemical window, and none was approved yet as none is entirely selective and sensitive to tau. These problems are being solved as new tracers emerge constantly. In this report, the first-generation tau tracers such as [¹¹C]PBB3, 2-arylquinoline (THK) series, [¹⁸F]T808, and [¹⁸F]AV-1451 ([¹⁸F]T807) are reviewed from an organic and radiochemistry perspective; thus the most effective chemical approach to synthesize these tracers is discussed. This would help to design novel tracers which can meet the challenges faced by the current tracers.