• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.6 no.2
• /
• pp.75-91
• /
• 2020

[^99mTc]Tc-Hexamethylpropylene amine oxime (HMPAO) is currently used as a regional cerebral blood flow imaging agent for single photon emission computed tomography (SPECT). The HMPAO ligand exists in two isomeric forms: d,l and meso showing different properties in vivo. Later studies indicated that brain uptake patterns of ^99mTc-complexes formed from separated enantiomers differed. Separation of enantiomers is difficult by fractional crystallizations method. Usually, the substance is obtained in low chemical yield in a time-consuming procedure. Furthermore, the final product still contains some impurity. So we have developed new efficient route for synthesis of R,R- and S,S-HMPAO enantiomeric compounds in 6-steps. Nucleophilic substitution (S_N2) reactions of 2,2-dimethylpropane-1,3-diamine either with S- (1a) or R-methyl2-chloropropanoate (1b) were performed to produce compounds R,R- (2a) or S,S-isomer (2b) derivatives protected with benzylchloroformate (Cbz), respectively. And then Weinreb amide and methylation reaction using Grignard reagent, oxime formation with ketone group and deprotectiion of Cbz group by hydrogenolysis gave S,S- (7a) or R,R-HMPAO (7b), respectively. Entaniomeric compounds were synthesied with high yield and purity without any undesired product. The 7a or 7b kits containing 10 ㎍ SnCl₂-2H₂O were labeled with ^99mTc with high radiolabeling yield (90%).

• The Korean Journal of Nuclear Medicine
• /
• v.29 no.1
• /
• pp.9-14
• /
• 1995

뇌졸증환자의 뇌 SPECT 소견상 나타나는 소뇌교차해리현상(crossed cerebellar diaschisis)은 잘 알려진 현상이다. 한편 간질 환자의 발작시 뇌 SPECT에서 반대편 소뇌에 혈류증가를 보이는 역교차해리현상(reverse type of crossed cerebellar diashisis)은 드물게 보고되었었다. 따라서 본 저자들은 발작시 뇌 SPECT에서 역교차해리현상의 빈도 및 간질병소를 찾는데 있어서의 유용성에 대해 알아보고자 하였다. 복합부분발작환자 중 임상적, 뇌파검사상 및 SPECT 소견등에서 간질병소가 일치하는 12명의 환자를 대상으로 하였다. 환자 모두에서 시행한 발작시 스캔은 발작중 혹은 환자가 aura를 호소할때 $^{99m}Tc$-HMPAO 15-20mCi를 정맥주입 후 시행하였으며 발작간 스캔은 11명의 환자에서 발작시 스캔 후 적어도 3일 간격을 두고 시행하였다. 간질병소는 우측측두엽이 6예, 좌측측두엽이 4예, 우측후두엽이 1예, 좌측전두엽이 1예 등이었다. 발작시 스캔상 간질병소 및 반대편 소뇌에 혈류가 증가하는 역해리현상은 모두 8명(75%)의 환자에서 나타났으며 특히 2명의 환자에서는 간질병소보다 반대편 소뇌의 동위원소 섭취가 더욱 뚜렸했다. 역해리현상을 보였던 환자의 발작간 스캔소견에서는 발작시 증가되었었던 소뇌의 동위원소 섭취가 7예에서 정상화되었고 나머지 1예에서는 감소되었다. 따라서 소뇌의 역교차해리현상은 발작시 뇌 SPECT의 자주 볼 수 있는 현상으로 간질병소의 편측화에 도움을 줄 수 있을 것으로 생각된다.

• The Korean Journal of Nuclear Medicine
• /
• v.29 no.1
• /
• pp.110-117
• /
• 1995

Tc-99m Labeled hexamethylenepropyleneamineoxime ([$^{99m}Tc$]-HMPAO) is a famous amino-oxime compound and is widely used to construct SPECT images of cerebral blood flow. To investigate the relationship between chemical structure and radiolabeling in these kind of diamine-oxime compounds, we synthesized seven compounds by Schiff's base formation and successive reduction with sodium borohydride. They were (RR/SS )-4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime (2), (RR/SS/meso)-4,8-diaza-3,9-dimethy-lundecane-2,10-dione bisoxime (4), (RR/SS/meso)-4,8-diaza-3,10-dimethyldodecane-2,11-dione bisoxime (5), (RR/SS/meso)-4,7-diaza-3,6,6,8-tetramethyldecane-2,9-dione bisoxime (8), (RR/SS/meso)-4,7-diaza-5,6-cyclohexyl-3,8-dimethyldecane-2,9-dione bisoxime (10), (RR/SS/meso)-3,4-bis(1-aza-2-methyl-3-oxime-1-butyl)-benzoic acid (12), and (RR/SS/ meso)-2,3-bis(1-aza-2-methyl-3-oxime-1-butyl) benzophenone (14). Chemical structures of all the synthesized compounds were identified by taking $^1H$ spectrum. Among them, 2 and 4 are propyleneamine oxime (PnAO), 6 is butyleneamine oxime (BnAO) and 8, 10, 12 and 14 are ethyleneamine oxime (EnAO). Each compound (0.5 mg) was incubated with stannous chloride (0.5 g - 8 g), carbonate-bicarbonate buffer (final concentration = 0.1 M, pH 7 - pH 10) and Tc-99m-pertechenate (1 ml). Tc-99m labeling of these compounds were checked by ITLC (acetone), ITLC (normal saline), reverse phase TLC (50 % acetonitrile) and ITLC (ethyl acetate). According to the results, EnAO's were not labeled by Tc-99m in any of above condition. About 11 % of maximum labeling efficiency was obtained with BnAO. However, 4 (PnAO) was labeled with Tc-99m to 85 % which is similar to the labeling efficiency of 2 (HMPAO). Hydrophilic impurity (9 % ) was the most significant problem with the labeling of 4, however, pertechnetate (3 % ) and colloid (3 %) were minor problem. In conclusion, we synthesized seven diamine blsoxlme compounds. Among them, four EnAO compounds were not labeled by Tc-99m. A BnAO was labeled poorly and two PnAO's were labeled well. These labeling can be explained by tertiary structure of their Tc-99m chelate.

• The Korean Journal of Nuclear Medicine
• /
• v.22 no.2
• /
• pp.147-156
• /
• 1988

알쯔하이머병 환자 11명, 우울증 환자 7명 그러고 정상 대조군 12명을 대상으로 $^{99m}Tc-HMPAO$ 뇌 SPECT를 이용하여 국소 뇌혈류 분포를 분석하여 다음과 같은 결과를 얻었다. 1) SPECT소견은 정상 대조군과 우울증군에서는 모두 정상이 있으나 알쯔하이머병군에서는 7명은 양측 측두엽 및 두정엽에, 3명은 편측 측두엽 및 두정엽에 그리고 1명은 전두엽에 뇌혈류 감소의 소견을 보였다. 2) 대뇌반구간 혈류분포의 변화를 비교하는 지수인 Cerebral asymmetry index는 정상 대조군에서 $0.08{\pm}0.03$, 알쯔하이머병군에서는 $0.11{\pm}0.04$ 그리고 우울증군에서는 $0.09{\pm}0.03$으로서 세 군간에 유의한 차이가 없었다. 3) 소뇌반구간 혈류분포의 변화를 비교하는 지수인 Percent index of cerebellar asymmetry는 정상 대조군에서 $0.4{\pm}0.7%$, 알쯔하이머병군에서 $-0.7{\pm}0.08%$ 그리고 우울증군에서 $-0.7{\pm}0.7%$로서 세군 간에 유의한 차이는 없었다. 4) 소뇌 계수치를 대조값으로 각 영역별 혈류분포의 변화정도를 비교하는 지수인 Region to cerebellum ratio는 우울증군에서는 정상 대조군과 유의한 차이를 보이지 않았으나 알쯔하이머병군에서는 양측 두정엽과 측두엽에서 유의한 감소를 보였다(p<0.05). 이상의 결과로 $^{99m}Tc-HMPAO$ 뇌 SPECT는 알쯔하이머병의 진단에 있어서 유용한 방법임을 알 수 있었다.

• The Korean Journal of Nuclear Medicine
• /
• v.29 no.3
• /
• pp.328-331
• /
• 1995

$^{99m}Tc$ labeled PnAO(propylene amine oxime) derivatives have been widely studied as brain perfusion agents. We synthesized and characterized a PnAO derivative, (RR/SS/ meso)-4,8-diaza-3,9-dimethylundecane-2, 10-dione bisoxime(PRODD). Proton-NMR spectroscopy and thin layer chromatography(silica gel) were performed for its characterization. PRODD was labeled with $^{99m}Tc$ using stannous chloride as reducing agent. The labeling efficiency was determined to be about 85%. Brain uptakes of $4.16{\pm}0.42$ %ID/g and $3.24{\pm}0.13$ %ID/g were found after 10min and 30min after intravenous injection. Brain-to-blood ratios were 1.17 and 0.75 at 10 and 30 minutes, which were lower than 1.3 and 1.9 of the ratios with commercial ${\pm}$-HMPAO. Autoradiographs of rat brain sections showed the gray matter to white matter ratios of $1.13{\pm}0.10$ at 30 min after intravenous injection, which was lower than $1.94{\pm}0.19$ of commercial $^{99m}Tc$-HMPAO. With the above findings, we concluded that the lipophilic $^{99m}Tc$-PRODD complex was able to cross the blood-brain barrier, however the complex showed lower uptake than $^{99m}Tc$-HMPAO in mouse or rat brains. We could suggest possibility that PRODD could be used as another $^{99m}Tc$ chelator.

• The Korean Journal of Nuclear Medicine
• /
• v.25 no.1
• /
• pp.17-26
• /
• 1991

뇌 혈류의 기능적 영상화는 간질병소의 국소화에 이용되고 있으며 측두엽성간질의 편측화에 여러가지 진단 방법이 이용되고 있으나 만족할만한 결과를 보이지 못하고 있다. 최근 PET또는 SPECT를 이용하여 측두엽성간질에서 발작 간에 측두엽 병소의 대사율 및 혈류의 감소가 나타나며, 이러한 소견은 발작 유발 병소의 편측화에 매우 유용할것이라는 보고들이 있다. 저자들은 측두엽성간질에서 간질 병소를 편측화 하는데에 $^{99m}Tc-HMPAO$ SPECT의 유용성을 평가 하고자 측두엽성간질 31예에서 발작 간의 $^{99m}Tc-HMPAO$ SPECT 소견, 뇌파, 자기 공명 영상 및 전산화 단층 소견을 비교하였다. SPECT 소견에 따른 나이, 병력 기간과 병발시 나이 등의 임상 지수 간에는 유의한 차이가 없었다. 31예의 환자중 23예에서(74.2%) 국소 뇌 혈류 감소를 보였으며 17예(54.8%)에서 측두엽에 관류 감소가 관찰 되었다. 비인두 뇌파 표준 뇌파는 24예(77.4%)에서 측두엽에 편측화를 보였으며 SPECT와 뇌파 양자가 모두 편측화된 경우 일치도는 8/12예 (66.7%) 였다. 16예에서 시행된 전산화 단층 영상은 모두 편측화를 보이지 못했으며 27예에서 시행된 자기 공명 영상에서는 단지 1예에서 편측화를 보였다. 이상의 결과로서 발작 간의 $^{99m}Tc-HMPAO$ SPECT는 측두엽성간질 병소의 편측화에 유용한 보조 검사로 생각된다.

• The Korean Journal of Nuclear Medicine
• /
• v.36 no.3
• /
• pp.166-176
• /
• 2002

Purpose: The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of $^{99m}Tc-HMPAO$ (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. Materials and Methods: The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and $^{99m}Tc-HMPAO$ SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the legion of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map (SPM99). Results: The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was $32.50{\pm}5.67%$. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Conclusion: Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann.

• The Korean Journal of Nuclear Medicine
• /
• v.28 no.1
• /
• pp.22-30
• /
• 1994

Encephalo-duro-arterio-synangiosis (EDAS) is a relatively new surgical procedure for treatment of childhood moyamoya disease. We assessed regional cerebral perfusion in moyamoya patients before (1.3 mo) and after (6.8 mo) EDAS with $^{99m}Tc$-HMPAO brain SPECT. A total of 21 EDAS operations in 17 moyamoya patients was included. Preoperative CT or MRI showed cerebral infarction in 14 patients and carotid angiography showed Suzuki grade I to V stenosis in 6%, 9%, 62%, 12% and 12% of the hemispheres respectively. Preoperative SPECT showed regional hypoperfusion in all patients, bilateral frontal and temporal lobes being the most frequently involved site. $4{\times}4$ pixel sized ROIs were applied on the frontotemporal cortex in 3 slice averaged transverse tomographic images. An index of regional perfusion was measured as: PI (%)=average F-T activity/average cerebellar activity${\times}100$ Pre-EDAS ipsilateral PI ranged from 23.7 to 98.4% (mean: $74.3{\pm}17%$) and increased significantly after operation ($81.4{\pm}17%$, p<0.001). Individual post-EDAS PI improved in 15/21 cases, showed no significant change in 5 and was slightly aggravated in 1. The amount of clinical improvement (${\Delta}CI$) was graded with a scale of 0 to 4 based on frequency and severity of TIA attacks. When patients were grouped according to pre-EDAS PI, group II (PI 70-89) showed a significantly higher ${\Delta}CI$ (3.3) compared to group I (PI< 70, 1.57) or group III (PI >90, 0.5) (P< 0.001). The amount of perfusion improvement (${\Delta}PI$) showed significant correlation with ${\Delta}CI$ (r=0.42, p=0.04). ${\Delta}PI$ did not, however, correlate with the amount of neovascularization assessed angiographically in 8 patients. Serial HMPAO SPECT is an useful noninvasive study for assessing perfusion improvement after EDAS in childhood moyamoya patients.

• 대한핵의학회:학술대회논문집
• /
• 1997.05a
• /
• pp.147-147
• /
• 1997

• 대한핵의학회:학술대회논문집
• /
• 2001.11a
• /
• pp.35.2-35.2
• /
• 2001