Tumor PET imaging with radiopharmaceuticals plays a major role in the understanding of tumor biological information and for diagnosis of tumorswith non-invasive methods. These radiopharmaceuticals can be divided into two categories radiopharmaceuticals for metabolic process imaging and for specific receptor imaging. Most tumor imaging radiopharmaceuticals such as [18F]FDG, [18F]FLT, and [11C]choline can be trapped in tumor cells by specific metabolic processes of each radiopharmaceutical and show an increase in metabolism of tumor regions. Unlike these compounds, the hypoxia imaging adiopharmaceuticals such as [18F]FMISO and [64Cu]ATSM are trapped by oxidative metabolic mechanisms under only hypoxic conditions of tumor cells. For tumor specific receptor imaging, [18F]FES for estrogen receptor positive breast cancer may be used and recent clinical results showed the possibility of evaluating tumor therapy responseby estrogen receptor imaging with [18F]FES. This paper gives an overview of the current status of tumor PET imaging adiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Anoxia ; Breast Neoplasms ; Chemistry, Pharmaceutical ; Diagnosis ; Estrogens ; Metabolism ; Radiopharmaceuticals*

OBJECTIVETo study the biologic process of energy metabolism in brain during acupuncture using positron emission tomography (PET) with 18F-2-desoxyglucose (18FDG) for further elucidation of the relationship between acupunctural signal and nerve system.

METHODSElectroacupuncture (EA) was applied on right lateral of a healthy volunteer and paralytic limbs of 4 patients with cerebral infarction at acupoints L14, LI11, ST36 and SP6 using Hans acupoint-nerve stimulator. PET imaging was conducted on the healthy subject or patients with the same posture before and during EA with GE Advance II PET system.

RESULTSPET showed that in the healthy subject, before EA, the glucose metabolism (GM) in bilateral cerebral cortex, bilateral thalamus, basal nuclei and cerebellum was almost symmetrical, but during EA, the GM in contralateral thalamus, contralateral frontal lobe and parietal lobe (motor and sensory area) increased obviously. While in the patients before EA, the GM in the infarcted area was significantly lower than that in the non-infarcted area, as compared with that observed with CT and MRI, it showed a similar figure but with bigger abnormal area. During EA, GM in the infarcted area increased with apparent reduction of size. Increased GM of focal area, widened cerebral cortex and decreased edematous area were shown in patients with larger infarction area. Quantitative analysis revealed evident change in local/total ratio of glucose and increase of GM change rate.

CONCLUSION(1) EA on limb acupoints of healthy subject could induce obvious increase of regional GM in brain and contralateral thalamus, contralateral frontal lobe and parietal lobe (motor and sensory area). (2) EA on acupoints of paralytic limbs could cause increase of GM in contralateral thalamus, contralateral frontal lobe and parietal lobe. Besides, GM also increased in the area with lowered GM before EA, accompanied with shrinkage or disappearance of lesion. (3) Acupuncture could evoke the function of brain cells and raise the GM in them.

Aged ; Brain ; diagnostic imaging ; metabolism ; Cerebral Infarction ; diagnostic imaging ; metabolism ; Electroacupuncture ; Energy Metabolism ; Female ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Humans ; Male ; Middle Aged ; Radiopharmaceuticals ; Random Allocation ; Tomography, Emission-Computed

Ever since it was first introduced as a method of scintigraphically measuring regional myocardial perfusion, myocardial perfusion study has been widely used in patients diagnosed or suspected with coronary artery diseases, and continuously improved upon. In addition to the technological enhancement of nuclear medicine equipments, the innovation of radiopharmaceuticals used in the cardiac exams were important contributors to such improvement. Besides the cardiac perfusion studies, new radiopharmaceuticals that visualize fat metabolism or receptors of the sympathetic nervous system have successfully been applied to clinical practice. More information can be collected before diagnosing coronary vascular disease, evaluating the patient's condition, or assessing therapeutic effects. In this review article, the clinical efficacy and characteristics of radiopharmaceutical products tailored for cardiac SPECT that are commonly used in Korea currently, plus the ones not being used yet but have proven value are briefly described.
Coronary Artery Disease ; Humans ; Korea ; Metabolism ; Nuclear Medicine ; Perfusion ; Radiopharmaceuticals* ; Sympathetic Nervous System ; Tomography, Emission-Computed, Single-Photon* ; Vascular Diseases

OBJECTIVETo evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood.

METHODSHerceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated.

RESULTSThe baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001).

CONCLUSIONStorage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.

Animals ; Antibodies, Monoclonal, Humanized ; pharmacokinetics ; Blood ; metabolism ; Cell Line, Tumor ; Drug Stability ; Humans ; Iodine Radioisotopes ; pharmacokinetics ; Rabbits ; Radiopharmaceuticals ; pharmacokinetics ; Trastuzumab

OBJECTIVETo synthesize the complex fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) for labeling IgG and investigate the in vitro stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG and its biodistribution in mice.

METHODSfac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) was synthesized and its radiochemical purity determined using polyamide membrane chromatography. IgG was directly labeled with fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) and the labeling ratio was determined using chromatography. The stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG in human serum albumin and normal saline was evaluated. ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was injected via the tail vein into 9 mice at the dose of 3.7×10⁴ Bq/100 µl, and SPECT image was obtained at 2, 4 and 12 h after the injection. The mice were sacrificed at these time points to measure the radioactivity and calculate the %ID/g in each organ.

RESULTSFac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) had a radiochemical purity of 82.48% and remained stable in vitro at room temperature within 4 h. The labeling ratio of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was 57.04% with a radiochemical purity exceeding 90%. In the solution of human serum albumin, the labeled IgG maintained a stable radiochemical purity, but in normal saline, its radiochemical purity was lowered to 20% at 24 h. After injection in mice, the labeled IgG was deposited mainly in the liver, spleen, kidneys, and the blood pool showed a sustained radioactivity.

CONCLUSION⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG prepared in this study has good stability in vitro and in vivo in 24 h and shows a biodistribution pattern similar to that of IgG protein in vivo. The intermediate fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) can meet the experimental requirement for labeling monoclonal antibodies and polypeptides.

Animals ; Immunoglobulin G ; administration & dosage ; metabolism ; Mice ; Mice, Inbred Strains ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution

Positron Emission Tomography(PET) is a new imaging modality to make biochemical metabolic images. Because biochemical changes precede anatomical changes in most of diseases including cancer, PET can detect earlier changes of diseases than conventional anatomical imaging modalities. PET can also characterize biochemical property of diseases. A PET center is composed of a medical cyclotron, synthesis system of radiopharmaceuticals and scanner. For PET oncology, several positron-emitting radiopharmaceuticals have been developed. Among them, F-18-fluorodeoxyglucose (FDG) is most frequently used. Higher rate of glucose metabolism has been observed in cancer cells. Like glucose, FDG is transported into the cancer cells and converted to FDG-6-phosphate by hexokinase. FDG-6-phosphate is trapped in the cytoplasm, and emits gamma rays to make PET images. The current application of FDG PET in oncology is in detection, differentiation, and staging of the primary tumors, grading malignancy, monitoring therapeutic response, and early detection of recurrence. Nowadays, PET is an established procedure for staging the diseases and detecting the recurrence in many cancers, especially the lung, colorectal, and head and neck cancers, melanoma, and lymphoma. PET is a regular part of medical insurance reimbursement in many developed countries, and becomes a valuable research tool in oncology as well as an important imaging modality in managing cancer patients.
Cyclotrons ; Cytoplasm ; Developed Countries ; Electrons* ; Gamma Rays ; Glucose ; Head ; Hexokinase ; Humans ; Insurance ; Lung ; Lymphoma ; Melanoma ; Metabolism ; Neck ; Radiopharmaceuticals ; Recurrence

OBJECTIVETo observe the effect of needling at Baihui(DU20), Shuigou(DU26) and Shenmen(HT7) on glucose metabolism in different regions of the brain in vascular dementia patients.

METHODSTen patients with vascular dementia were randomized into 2 groups, and the patients in the control group received the treatment with needling in the routine acupoints for hemiplegia (chosen from 6 Yang meridians of the hand and foot), while those in treatment group received needling at 3 additional acupoints, namely Baihui(DU20), Shuigou(DU26) and Shenmen(HT7), which were specific for dementia treatment. All the patients were examined by positron-emission tomography(PET) to detect the glucose metabolism in different brain regions before and after acupuncture treatment by means of semiquantitative analysis of the average values of radioactive count in the brain regions.

RESULTSNeedling at the additional 3 acupoints could obviously enhance glucose metabolism in the bilateral frontal lobes, bilateral thalamus, temporal lobe and lentiform nucleus on the uncompromised side.

CONCLUSIONThe effect of needling at Baihui(DU20), Shuigou(DU26) and Shenmen(HT7) on vascular dementia is closely related to improved cerebral glucose metabolism.

Acupuncture Points ; Acupuncture Therapy ; Aged ; Brain ; metabolism ; Dementia, Vascular ; metabolism ; pathology ; therapy ; Female ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Radiopharmaceuticals ; Treatment Outcome

Soft tissue uptake of Tc-99m labeled bone seeking agents, such as Tc-99m 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD), is commonly seen in clinical practice, even though bone scintigraphy is mainly used to detect bone disease. However, gastric uptake of bone agents in patients with gastric cancer is very rare. And it has been reported that calcified gastric adenocarcinoma appears in only about 5% of all gastric cancer. We report a rare case of bone scintigraphy, single photon emission computed tomography and computed tomography fusion images that demonstrated diffuse gastric uptake of Tc-99m DPD in a patient with advanced gastric cancer.
Stomach Neoplasms/*metabolism ; Stomach/*metabolism ; Radiopharmaceuticals/*pharmacokinetics ; Organotechnetium Compounds/diagnostic use/*pharmacokinetics ; Male ; Humans ; Diphosphonates/diagnostic use/*pharmacokinetics ; Bone and Bones/*radionuclide imaging ; Aged

OBJECTIVE: To evaluate the effectiveness of IL-10 in suppressing 18F-FDG uptake in the inflammatory granuloma of SD rats. METHODS: Eight SD rats were killed, and their blood was collected sterily. After centrifugion, the white blood cells were incubated in PRMI 1640 for 3 days. Then each culture flask of white blood cells was divided into two equal parts. To one group was added 0.2 mL IL-10 solution (0.1 mg/mL); to the control was added with 0.2 mL of 0.9% sodium chloride solution. All cells were then incubated for 120 minutes at 37 degree, after which 18F-FDG (1.85 MBq) was added. Sixty minutes later, the cells were washed twice with PBS and the extent of uptake 18F-FDG determined. In vivo, an inflammatory granuloma was produced by hypodermic injection of rats with a mixture of Freund's complete adjuvant, bovine serum albumin and talcum powder. Each rat was maintained for 8 weeks. Imaging of the inflammatory granulomas was performed using the 18F-FDG signal. IL-10 was injected into SD rats at 10 μg/kg of body weight. Sixty minutes later, 7.4 MBq of 18F-FDG were injected, and, after a further 60 minutes, the rats underwent a PET-CT scan. The region of interest (ROI) of the inflammatory granuloma was delineated and the standard uptake value (SUV) calculated. A second PET-CT scan was done without IL-10 on the next day. The granulomatous tissue underwent pathological examination. RESULTS: In the intro test, the with blood cell uptaking ratio of 18F-FDG was (50.3±6.7)% without IL-10, and (34.6±3.5)% with IL-10(t=8.9, P<0.01). IL-10 suppressed the rat white blood cell uptaking 18F-FDG. In the PET-CT scan, the SUV of ROI on inflammatory granuloma was 1.7±0.4 with IL-10 and 2.1±0.3 without IL-10 (t=20.6, P<0.01). IL-10 suppressed the inflammatory granuloma uptaking 18F-FDG. CONCLUSION IL-10 can suppress the inflammatory granuloma of SD rats uptaking 18F-FDG.
Animals ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Freund's Adjuvant ; Granuloma ; chemically induced ; metabolism ; Interleukin-10 ; pharmacology ; Lung Diseases ; chemically induced ; metabolism ; Male ; Radiopharmaceuticals ; pharmacokinetics ; Rats ; Serum Albumin, Bovine

OBJECTIVETo establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.

METHODS(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.

RESULTS(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.

CONCLUSIONThe (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.

Animals ; Carbon Radioisotopes ; Contrast Media ; chemical synthesis ; Isoquinolines ; adverse effects ; chemical synthesis ; Mice ; Positron-Emission Tomography ; Radioligand Assay ; Radiopharmaceuticals ; adverse effects ; chemical synthesis ; Receptors, GABA-A ; metabolism