Anatomical Morphometric Study of the Cervical Uncinate Process and Surrounding Structures

OBJECTIVE: The purpose of this study is to elucidate the anatomic relationships between the uncinate process and surrounding neurovascular structures to prevent possible complications in anterior cervical surgery. METHODS: Twenty-eight formalin-fixed cervical spines were removed from adult cadavers and were studied. The authors investigated the morphometric relationships between the uncinate process, vertebral artery and adjacent nerve roots. RESULTS: The height of the uncinate process was 5.6-7.5 mm and the width was 5.8-8.0 mm. The angle between the posterior tip of the uncinate process and vertebral artery was 32.2-42.4degrees. The distance from the upper tip of the uncinate process to the vertebral body immediately above was 2.1-3.3 mm, and this distance was narrowest at the fifth cervical vertebrae. The distance from the posterior tip of the uncinate process to the nerve root was 1.3-2.0 mm. The distance from the uncinate process to the vertebral artery was measured at three different points of the uncinate process : upper-posterior tip, lateral wall and the most antero-medial point of the uncinate process, and the distances were 3.6-6.1 mm, 1.7-2.8 mm, and 4.2-5.7 mm, respectively. The distance from the uncinate process tip to the vertebral artery and the angle between the uncinate process tip and vertebral artery were significantly different between the right and left side. CONCLUSION: These data provide guidelines for anterior cervical surgery, and will aid in reducing neurovascular injury during anterior cervical surgery, especially in anterior microforaminotomy.

Morphometric Relationship between the Cervicothoracic Cord Segments and Vertebral Bodies

OBJECTIVE: The objective of this study was to investigate the morphologic characteristics between the vertebral body and the regions of the cervical and thoracic spinal cords where each rootlets branch out. METHODS: Sixteen adult cadavers (12 males and 4 females) with a mean age of 57.9 (range of 33 to 70 years old) were used in this study. The anatomical relationship between the exit points of the nerve roots from the posterior root entry zone at each spinal cord segment and their corresponding relevant vertebral bodies were also analyzed. RESULTS: Vertical span of the posterior root entry zone between the upper and lower rootlet originating from each spinal segment ranged from 10-12 mm. The lengths of the rootlets from their point of origin at the spinal cord to their entrance into the intervertebral foramen were 5.9 mm at the third cervical nerve root and increased to 14.5 mm at the eighth cervical nerve root. At the lower segments of the nerve roots (T3 to T12), the posterior root entry zone of the relevant nerve roots had a corresponding anatomical relationship with the vertebral body that is two segments above. The posterior root entry zones of the sixth (94%) and seventh (81%) cervical nerve roots were located at a vertebral body a segment above from relevant segment. CONCLUSION: Through these investigations, a more accurate diagnosis, the establishment of a better therapeutic plan, and a decrease in surgical complications can be expected when pathologic lesions occur in the spinal cord or vertebral body.

The Changes in Range of Motion after a Lumbar Spinal Arthroplasty with Charitetrade mark in the Human Cadaveric Spine under Physiologic Compressive Follower Preload : A Comparative Study between Load Control Protocol and Hybrid Protocol

OBJECTIVE: To compare two testing protocols for evaluating range of motion (ROM) changes in the preloaded cadaveric spines implanted with a mobile core type Charite(TM) lumbar artificial disc. METHODS: Using five human cadaveric lumbosacral spines (L2-S2), baseline ROMs were measured with a bending moment of 8 Nm for all motion modes (flexion/extension, lateral bending, and axial rotation) in intact spine. The ROM was tracked using a video-based motion-capturing system. After the Charite(TM) disc was implanted at the L4-L5 level, the measurement was repeated using two different methods : 1) loading up to 8 Nm with the compressive follower preload as in testing the intact spine (Load control protocol), 2) loading in displacement control until the total ROM of L2-S2 matches that when the intact spine was loaded under load control (Hybrid protocol). The comparison between the data of each protocol was performed. RESULTS: The ROMs of the L4-L5 arthroplasty level were increased in all test modalities (p < 0.05 in bending and rotation) under both load and hybrid protocols. At the adjacent segments, the ROMs were increased in all modes except flexion under load control protocol. Under hybrid protocol, the adjacent segments demonstrated decreased ROMs in all modalities except extension at the inferior segment. Statistical significance between load and hybrid protocols was observed during bending and rotation at the operative and adjacent levels (p < 0.05). CONCLUSION: In hybrid protocol, the Charite(TM) disc provided a relatively better restoration of ROM, than in the load control protocol, reproducing clinical observations in terms of motion following surgery.

Small Animal PET Imaging with 124IFIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model / 핵의학분자영상

PURPOSE: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the develoopement of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-beta-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. MATERIAL AND METHODS: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. RESULTS: Specific accumulation of [125I]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small aninal PET, [124I]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. CONCLUSION: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

Establishment of a Hepatocellular Carcinoma Cell Line Expressing Dual Reporter Genes: Sodium Iodide Symporter (NIS) and Enhanced Green Fluorescence Protein (EGFP) / 핵의학분자영상

PURPOSE: Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. MATERIALS AND METHODS: A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. RESULTS: The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, T(1/2) of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. CONCLUSION: A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene.

Alpha-emitting Radioisotopes Production for Radioimmunotherapy / 핵의학분자영상

This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of 213Bi, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.

Synthesis and Preliminary Evaluation of 9-(4-18FFluoro-3-hydroxymethylbutyl) Guanine (18FFHBG) in HSV1-tk Gene Transduced Hepatoma Cell / 핵의학분자영상

PURPOSE: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. MATERIALS AND METHODS: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[18F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [18F]FHBG were performed, and was analyzed correlation between [18F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. RESULTS: [18F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 GBq/micro mol. Specific accumulation of [18F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [18F]FHBG was retained inside of cells. The uptake of [18F]FHBG was showed a highly significant linear correlation (R2=0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. CONCLUSION: [18F]FHBG appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

Production of 18FF2 Gas for Electrophilic Substitution Reaction / 핵의학분자영상

PURPOSE: Electrophilic 18F (T1/2=110 min) radionuclide in the form of [18F]F2 gas is of great significance for labeling radiopharmaceuticals for positron emission tomography (PET). However, its production in high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of [18F]F2 for the electrophilic substitution reaction. MATERIALS AND METHODS: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the 18O(p,n)18F reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched 18O2 was irradiated with protons for 18F production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas (1% [19F]F2/Ar) was loaded into the target chamber, following a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and 18O2 loading pressure. RESULTS: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97 % enriched 18O2, 13.2 MeV protons, 30 micro A, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% [19F]fluorine/argon gas, 13.2 MeV protons, 30 micro A, 20-30 min irradiation), the recovery of [18F]fluorine for synthesis. The yield of [18F]fluorine at EOB (end of bombardment) was achieved around 34+/-6.0 GBq (n>10). CONCLUSION: The production of 18F electrophilic agent via 18O(p,n)18F reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of [18F]fluorine. These results suggest the possibility to use [18F]F2 gas as a electrophilic substitution agent.

A Study on Preparation of 3'-18FFluoro-3'-deoxythymidine and Its Biodistribution in 9L Glioma Bearing Rats / 핵의학분자영상

PURPOSE: Several radioisotope-labeled thymidine derivatives such as [11C]thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with [11C]thymidine due to rapid in vivo degradation and its short physical half-life. 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) and compared with [18F]FET and [18F]FDG in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor bearing rats. MATERIAL AND METHOD: For the synthesis of [18F]FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with 18F was performed in acetonitrile at 120 degrees C and deproteced with 0.5 N HCl. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. RESULTS: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of [18F]FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were 1.61+/-0.34, 1.70+/-0.30 and 9.33+/-2.22, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. CONCLUSION: The uptake of [18F]FLT in tumor was higher than in normal brain and PET image of [18F]FLT was acceptable. These results suggest the possibility of [18F]FLT as an imaging agent for brain tumor.

A Study on the Synthesis and Its Biodistribution of C - 11 and F - 18 Labelled Choline / 대한핵의학회잡지

No abstract available.

Analysis of Heavy Metals in 201TlTlCl Injection Using Polarography / 대한핵의학회잡지

PURPOSE: Thallous-201 chloride produced at Korea Cancer Center Hospital(KCCH) is used in detecting cardiovascular disease and cancer. Thallium impurity can cause emesis, catharsis and nausea, so the presence of thallium and other metal impurities should be determined. According to USP and KP, their amounts must be less than 2 ppm in thallium and 5 ppm in total. In this study, the detection method of trace amounts of metal impurities in [201Tl]TlCl injection with polarography was optimized without environmental contamination. MATERALS AND METHODS: For the detection of metal impurities, Osteryoung Square Wave Stripping Voltammetry method was used in Bio-Analytical System (BAS) 50W polarograph. The voltammetry was composed of Dropping Mercury Electrode (DME) as a working electrode, Ag/AgCl as a reference electrode and Pt wire as a counter electrode. Square wave stripping method, which makes use of formation and deformation of amalgam, was adopted to determine the metal impurities, and pH 7 phosphate buffer was used as supporting electrolyte. RESULTS: T1, Cu and Pb in thallous-201 chloride solution were detected by scanning from 300 mV to -800 mV. Calibration curves were made by using TlNO3, CuSO4 and Pb(NO3)2 as standard solutions. Tl was confirmed at -450 mV peak potential and Cu at -50 mV. Less than 2 ppm of Tl and Cu was detected and Pb was not detected in KCCH-produced thallous-201 chloride injection. CONCLUSION: Detection limit of thallium and copper is approximately 50 ppb with this method. As a result of this experiment, thallium and other metal impurities in thallous-201 chloride injection, produced at Korea Cancer Center Hospital, are in the regulation of USP and KP. Polarograph could be applied for the determination of metal impurities in the quality control of radiopharmaceuticals conveniently without environmental contamination.

Biodistribution of 3-iodo-O-mythyl-L-alpha-methyltyrosine in Tumor Bearing Rats: A Comparison Study with L-3-iodo-alpha-methyltyrosine / 대한핵의학회잡지

PURPOSE: The aim of this sutdy was to evaluate the feasibility of 3-[131I]Iodo-O-methyl-L-a-methyltyrosine ([131I]OMINT) as an agent for tumor image. MATERIALS AND METHODS: After synthesis of 4-O-methyl-L-a-methyltyrosine (OMAMT), OMAMT was labeled with 131I using Iodogen method. In viro cellular uptake study was performed using 9 L gliosarcoma cells at various time points upto 4 hr. The biodistribution (five rats implanted with the 9 L gliosarcoma cells per group) was evaluated at 30 min, 2 hr, 24 hr after iv injection of 3.7 MBq [131I]OMIMT or L-3-[131I]iodo-a-methyltyrosine ([131I]IMT). Gamma camera images were obtained at 30min, 2 hr, and 24 hr. RESULTS: [131I]OMINT uptake was 3.3 times and 2.5 times higher than [131I]IMT uptake at 30 min and 60 min, respectively and same after 2 hr in in vitro sutdy using 9L gliosarcoma cells. Maximum accumulation in tumor occurred at 30 min for both [131IOMINT and [131I]IMT in tumor bearing rats. The tumor uptake of [131I]OMINT was significantly higher than that of [131I]IMT in tumor bearing rats. The tumor uptake of [131I]OMIMT was significantly higher than that of [131I]IMT at early time point studied (3.74 +/- 0.48 vs 0.38 +/- 0.17% ID/g at 30 min and 2.40 +/- 0.17 vs 0.24 +/- 0.03% ID/g at 2 hr, respectively, p<0.01). However, the tumor uptake of both radiolabels were not significantly different at 24 hr (0.04 +/- 0.01 vs 0.05 +/- 0.01% ID/g). Tumor was visualized as early as at 30 min in gamma camera images. CONCLUSION: These data suggested that [131I]OMIMT might be a useful tumor imaging agent and has more advantage for the tumor imaging compared to [131I]IMT.