• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.24-30
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• 2009

Purpose: Today, Prostate cancer has been gradually increasing, according to the change of internal incidence rate of cancer. Generally, prostate cancer has lead to dead over 90%, in case of metastasis of lymph node and bone. So, innovative development of new radiopharmaceutical and imaging modality is progressed for detection of that metastasis, in nuclear medicine, now. Therefore, this study shows the usefulness of $^{18}F$-Fluoride PET/CT improved diagnosability on bone metastasis of prostate cancer. Materials and Methods: In this study, 33 male patients with prostate cancer were examined (The mean age: $67.8{\pm}10.2$ years old). Every patient was done each whole body bone scan (WBBS) and $^{18}F$-Fluoride positron emission tomography/computed tomography ($^{18}F$-Fluoride PET/CT). And then, using Receiver Operating Characteristic Curve (ROC curve), each sensitivity and specificity of two modalities was measured and compared with. Results: In 22 patients (66.6%) of all, bone metastasis was detected. And, in WBBS, sensitivity was 63.6%, specificity, 81.8%; in $^{18}F$-Fluoride PET/CT, sensitivity was 100% and specificity was 90.9%. As a result of ROC curve, AUROC (The Area under an ROC) of WBBS was 0.778, and that of $^{18}F$-Fluoride PET/CT, 0.942. Conclusions: $^{18}F$-Fluoride PET/CT was higher both sensitivity and specificity than WBBS, and it was valuable to detect bone metastasis of prostate cancer more definitely, with 3D imaging realization. Also, in $^{18}F$-Fluoride PET/CT, physiological images were acquired in more short time than WBBS, so, it was possible to reduce patient's waiting time and complaint. Therefore, it is considered that $^{18}F$-Fluoride PET/CT is able to improve diagnosability by offering more accurate images, as cuts in a share of high cost.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.253-258
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• 2009

Bone scintigraphy using $^{99m}$Tc-labeled phosphate agents has long been the standard evaluation method for whole skeletal system. However, recent shortage of $^{99m}$Tc supply and advanced positron emission tomography (PET) technology evoked the attention to surrogate radiopharmaceuticals and imaging modalities for bone. Actually, fluorine-18 ($^{18}$F) was the first bone seeking radiotracer before the introduction of $^{99m}$Tc-labeled agents even though its clinical application failed to become pervasive anymore after the rapid spread of Anger type gamma camera systems in early 1970s. However, rapidly developed PET technology made us refocus on the usefulness of $^{18}$F as a PET tracer. Early study comparing $^{18}$F-Na PET scan and planar bone scintigraphy reported that PET has higher sensitivity and specificity in the diagnosis of metastatic bone lesions than planar bone scan. Subsequent reports comparing between PET and both planar and SPECT bone image also revealed better results of PET scan in similar study groups. Rapid clinical application of PET/CT also accumulated considerable amount of experiences in skeletal evaluation and this modality is known to have better diagnostic power than stand alone PET system as well as bone scan. Furthermore $^{18}$F-Na PET/CT revealed better or at least equal results in detection of primary and metastatic bone lesions compared with CT and MRI. Therefore, it is obvious that $^{18}$F-Na PET/CT has potential to become new imaging modality for practical skeletal evaluation so continuous and careful evaluation of this modality and radiopharmaceutical must be required.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.2
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• pp.91-99
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• 2009

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography(PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with $^{18}F$-fluorine. In this review we describe recent methods and novel trends for the introduction of $^{18}F$-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic $^{18}F$-fluorination of some halo- and mesyloxyalkanes to the corresponding $^{18}F$-fluoroalkanes with $^{18}F$-fluoride obtained from an $^{18}O(p,n)^{18}F$ reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for $^{18}F$-fluorine labeling. Ionic liquid method is rapid and particularly convenient because $^{18}F$-fluoride in $H_2O$ can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with $^{18}F$-fluorine for PETimaging, and it is illustrated by the synthesis of $^{18}F$-fluoride radiolabeled molecular imaging probes, such as $^{18}F$-FDG, $^{18}F$-FLT, $^{18}F$-FP-CIT, and $^{18}F$-FMISO, in high yield and purity and in shorter times compared to conventional syntheses.

• The Korean Journal of Nuclear Medicine Technology
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• v.23 no.2
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• pp.38-42
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• 2019

Purpose Although computed tomography (CT) is used for coronary artery calcification, it is difficult to differentiate between high risk microcalcifications. Studies have shown that $^{18}F$-sodium fluoride ($^{18}F-NaF$) is very useful for the diagnosis of microcalcifications. In this study, we aimed to evaluate the usefulness of $^{18}F-NaF$ PET imaging in quantitative evaluation of calcification. Materials and Methods A total of 45 patients ($67.1{\pm}6.9years\;old$) were injected with 250 MBq of $^{18}F-NaF$ for 1 hour and images were acquired for 30 minutes. All patients underwent CT angiography (CTAngiography, CTA) before the PET scan. The SUVmax of calcification was measured and the background radioactivity of the left atrium was measured to determine Target to Background (TBR) and quantitatively analyzed. High risk group was classified through ROC curve (Receiver Operating Characteristic Curve). Results There were 226 coronary artery calcifications in the cohort and SUVmax was $1.15{\pm}0.39$. Of the 28 patients (62%), 58 were classified as high risk (TBR > 1.25). The remaining 168 were $TBR{\leq}1.25$. Conclusion $^{18}F-NaF$ PET images were available for quantitative assessment of microcalcifications and could be classified into high-risk groups. The combination of angiographic CT and $^{18}F-NaF$ PET may be a new method for early diagnosis of high-risk microcalcifications.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2006.08a
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• pp.52-52
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• 2006

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.48-53
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• 2019

A bone metastasis is an important factor for prognosis and treatment of breast or prostate cancer patients. [$^{18}F$]Sodium fluoride ([$^{18}F$]NaF) is a PET radiopharmaceutical that can detect bone metastasis. Conventional [$^{18}F$]NaF production process included radioactive metal impurities because the product was prepared by adding saline after beam irradiation to $[^{18}O]H_2O$. In this study, we apply the method of removing radionuclidic impurities. To meet the criteria prescribed by GMP in quality control, we designed the custom-made [$^{18}F$]NaF automatic module. The mean radiochemical yield was $82.1{\pm}4.4%$ (n = 32) productions for 3 years) and the total preparation time was 4 min. The final produced [$^{18}F$]NaF solution meets the USP criteria for quality control. Thus, this fully automated system is validated for clinical use.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.317-325
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• 2007

Purpose: Biological parameters can be quantified using dynamic PET data with compartment modeling and Nonlinear Least Square (NLS) estimation. However, the generation of parametric images using the NLS is not appropriate because of the initial value problem and excessive computation time. In irreversible model, Patlak graphical analysis (PGA) has been commonly used as an alternative to the NLS method. In PGA, however, the start time ($t^*$, time where linear phase starts) has to be determined. In this study, we suggest a new Multiple Linear Analysis for irreversible radiotracer (MLAIR) to estimate fluoride bone influx rate (Ki). Methods: $[^{18}F]Fluoride$ dynamic PET scans was acquired for 60 min in three normal mini-pigs. The plasma input curve was derived using blood sampling from the femoral artery. Tissue time-activity curves were measured by drawing region of interests (ROls) on the femur head, vertebra, and muscle. Parametric images of Ki were generated using MLAIR and PGA methods. Result: In ROI analysis, estimated Ki values using MLAIR and PGA method was slightly higher than those of NLS, but the results of MLAIR and PGA were equivalent. Patlak slopes (Ki) were changed with different $t^*$ in low uptake region. Compared with PGA, the quality of parametric image was considerably improved using new method. Conclusion: The results showed that the MLAIR was efficient and robust method for the generation of Ki parametric image from $[^{18}F]Fluoride$ PET. It will be also a good alternative to PGA for the radiotracers with irreversible three compartment model.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.6
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• pp.561-565
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• 2007

Purpose: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Materials and Methods: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound $[^{18}F]$TPP via two step nucleophilic substitution of no-carrier-added $[^{18}F]$fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and $K_2CO_3$. Result: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound $[^{18}F]$TPP was synthesized in $10\sim15%$ yield. The radiochemical purity of the $[^{18}F]$TPP was $95.57{\pm}0.51%$ (n=11). Conclusion: $[^{18}F]$TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply $[^{18}F]$TPP in preclinical or clinical researches.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.51-56
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• 2018

Azeotropic drying process is routinely applied to enhance nucleophilicity of $[^{18}F]$fluoride ion during the nucleophilic production of PET radiotracers; however, the drying process requires usually 15-25 min. Due to the high demand of employing fluorine-18 ($t_{1/2}=109.8min$) in PET radiopharmaceutical production, several research groups have focused on the method development, obviating tedious removal process of the residual target water ($[^{18}O]H_2O$) for $[^{18}F]$fluoride ion complex to be used in radiofluorination. Some development in radiofluorination in a mixed organic solvent system was demonstrated with various aliphatic substrates, but only kryptand as a phase transfer agent was utilized in the reported method. Here, we extend to investigate the development scope of applicability with basic alkyl ammonium salt as a phase transfer agent through the extensive elution efficiency study and radiofluorination outcome for aliphatic radiofluorination.

• Journal of Radiation Industry
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• v.4 no.1
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• pp.7-11
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• 2010

Clotrimazole [1-{(2-chlorophenyl)-diphenylmethyl}-1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [$^{18}F$]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [$^{18}F$]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/$K_2CO_3$ for 10 min at $80^{\circ}C$. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove $^{18}F^-$. The [$^{18}F$]F-clotrimazole derivatives were synthesized with a 20~25% yield. In the radiofluorination step, we used acetonitrile and DMSO as a solvent and observed a higher yield at the acetonitrile (25%) reaction compared with the DMSO reaction (5%).