Sang Eun Kim

Brain Tumor Imaging with 99mTc-tetrofosmin: Comparison with 201Tl, 99mTc-MIBI, and 18F-fluorodeoxyglucose

The purpose of the present study was to assess the ability of technetium-99m-tetrofosmin (99mTc-TF) to predict tumor malignancy and to compare its uptake with that of thallium-201 (201Tl), technetium-99m-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) and fluorine-18-fluorodeoxyglucose (18F-FDG) in brain tumors. 99mTc-TF single-photon emission computed tomography (SPECT) imaging was performed in 22 patients with brain tumors and 3 healthy controls. Some of the patients underwent 201Tl (n = 12) and 99mTc-MIBI SPECT (n = 14) and 18F-FDG positron emission tomography (PET) (n = 12). The radioactivity ratio of tumor to contralateral normal tissue (T/N) and the ratio of tumor to contralateral white matter (T/WM) were calculated in SPECT and PET images, respectively. In healthy controls, 99mTc-TF uptake was seen only in scalp, in the choroid plexus and pituitary gland, but not in normal cerebral parenchyma. TF T/N in low grade gliomas (2.8 ± 0.4) was significantly lower than that in high grade gliomas (22.5 ± 29.8) and malignant non-gliomas (8.3 ± 2.8) without overlap of values (p = 0.003 and p = 0.014, respectively). TF T/N was significantly correlated with MIBI T/N (ρ = 0.92, p = 0.001), Tl T/N (ρ = 0.72, p = 0.017), and FDG T/WM (ρ = 0.65, p = 0.031). There was an excellent agreement between TF T/N and MIBI T/N values on linear regression analysis (MIBI T/N = −0.63 + 0.97 × TF T/N). These preliminary results indicate that SPECT imaging with 99mTc-TF may be useful for the non-invasive grading of brain tumors. They also suggest that 99mTc-TF and 99mTc-MIBI may accumulate in brain tumors by a similar mechanism or in relation to a similar process of tumor cell proliferation.

Development of a miniature scintillation camera using an NaI(Tl) scintillator and PSPMT for scintimammography

We have developed a small scintillation camera dedicated to breast imaging and have evaluated the performance of the system. In order to increase the limited field of view (FOV) determined by the size of a position-sensitive photomultiplier tube (PSPMT), the imaging characteristics of a diverging hole collimator (DHC) were also investigated. The small scintillation camera system consists of an NaI(Tl) crystal (60 mm x 60 mm x 6 mm) coupled to a Hamamatsu R3941 PSPMT, a resistor chain circuit, preamplifiers, nuclear instrument modules, an analogue to digital converter and a PC for control and display. The intrinsic energy resolution of the system was 12.9% FWHM at 140 keV. The spatial resolution was measured using a line-slit mask and 99mTc point sources and was 3.1 mm FWHM. The intrinsic sensitivity of the system was approximately 162 counts/s kBq(-1). The DHC made it possible to image a larger FOV (75 x 75 mm2 at the surface of collimator) than a parallel-hole collimator (60 x 60 mm2). The system sensitivity obtained using the DHC gradually decreased with distance (3% at 1 cm, 6% at 2 cm and 9% at 3 cm). The results demonstrate that the system developed in this study could be utilized clinically to image malignant breast tumours. A DHC can be employed to expand the FOV of the system confined by the size of PSPMT with a modest compromise in the performance of the system.

Gating provides improved accuracy for differentiating artifacts from true lesions in equivocal fixed defects on technetium 99m tetrofosmin perfusion SPECT

BackgroundBecause equivocal fixed perfusion defects on single photon emission computed tomography (SPECT) often cause a diagnostic dilemma in patients with suspected coronary artery disease (CAD), we used receiver-operating characteristic (ROC) curve analysis to evaluate the degree of increased accuracy provided by adding gated images for interpretation of such cases.Methods and resultsOne hundred five (29%) of 365 consecutive patients undergoing technetium 99m tetrofosmin gated SPECT for evaluation of CAD demonstrated an equivocal fixed defect. Two independent observers graded the probability for true lesion with a 5-point system over 3 steps of interpretation: reviewing tomographic images alone (step 1), adding projection images (step 2), and adding gated cine images (step 3). Based on clinical criteria, 66 patients were categorized as disease negative and 25 as disease positive, while the final diagnosis was undetermined in 14 cases. Diagnostic performance was significantly higher at step 3 than at step 1 for both observers (p<0.05 and <0.0001) and at step 2 for observer B (p<0.005). The maximum accuracy increased from 78.0% to 80.2% at step 2 to 84.6% to 86.8% at step 3. Moreover, the agreement of interpretation between the 2 observers was higher at step 3 (κ=0.53) than at step 1 (ϰ=0.29) or step 2 (ϰ=0.25).ConclusionIn patients showing an equivocal fixed defect on 99mTc tetrofosmin SPECT, gated cine images provide improved differential accuracy and enhanced objectivity of interpretation by reducing interobserver variance.

4-[18F]fluoromethylbenzylsulfonate ester: a rapid and efficient synthetic method for the N-[18F]fluoromethylbenzylation of amides and amines☆

We have prepared 4-[18F]fluoromethylbenzylsulfonate esters as fluoromethylbenzylating agents. These agents are readily prepared by an [18F]fluoride ion displacement of the corresponding bissulfonate esters. The application of these 4-[18F]fluoromethylbenzylsulfonate esters to N-alkylation reaction of spiperone and 1-phenylpiperazine shows that the products 3-N-(4-[18F]fluoromethylbenzyl)spiperone and 1-N-(4-[18F]fluoromethylbenzyl)-4-phenylpiperazine are rapidly produced with high radiochemical yields under a no-carrier-added condition.

A simple and efficient in vitro method for metabolism studies of radiotracers.

In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.

Synthesis and biological evaluation of 1-(4-[18f]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase

We synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[(18)F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[(18)F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40-52%) and with high effective specific activity (30-38 GBq/micromol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[(18)F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.

Synthesis of radioiodine-labeled 2-phenylethyl 1-thio-β-d-galactopyranoside for imaging of LacZ gene expression

A potent inhibitor of beta-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-beta-D-galactopyranoside (PETG), was radioiodinated for noninvasive imaging of LacZ gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2-(4-bromophenyl)ethanethiol was prepared and attached to the C-1 position of beta-D-galactose pentaacetate under conditions that resulted in the exclusive formation of the beta anomer. The bromo group of PETG was converted to the tributylstannyl group where radioiododemetallation was carried out. Radioiodine-labeled PETG tetraacetate was purified by HPLC, which can be used as a prodrug for biological evaluation or hydrolyzed to 2-(4-[123I/125I]iodophenyl)ethyl 1-thio-beta-D-galactopyranoside ([123I/125I]7) under basic conditions. The resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical yield (decay-corrected) and with specific activity of 46-74 GBq/micromol.