123I放射性药物简介

根据日本放射性同位素协会的报告，2005年在临床用放射性同位素中123^I活度值位列第三，仅次于99^Tc^m和201^TI（不包含医院制作的18^F）。虽然目前核医学诊断仍以99^Tc^m为主，但123^I扩充了单光子显像的应用范围，并且与99^Tc^m比较，123^I更适合于标记单克隆抗体及受体配体。     

美国药典论坛收载的碘[^131I／^123I]苄胍注射液

介绍了美国药典论坛收载的碘「＾１３１Ｉ／＾１２３Ｉ」苄注射液标准。     

Whole-body kinetics and dosimetry ofl-3-[123I]iodo-α-methyltyrosine

The synthetic amino acidl-3-[¹²³I]iodo--methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370–550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%±11.5% at 1.5 h p.i., 63.0%±15.7% at 3 h p.i. and 74.6%±9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.     

Synthesis of 2-[123I and 124I]-iodoisonicotinic acid hydrazide—potential radiotracers for tuberculosis

The radiochemical syntheses of methyl 2-[¹²³I]-iodoisonicotinate, 2-[¹²³I]-iodoisonicotinic acid hydrazide and 2-[¹²⁴I]-iodoisonicotinic acid hydrazide was accomplished. Iodine-123 was incorporated in the methyl ester molecule by an exchange reaction in glacial acetic acid. The average efficiency of iodine exchange reaction was (92.6 ± 4.5)%. This radiotracer was extracted with ether and the solvent was evaporated. The residue was re-dissolved in anhydrous ethanol and treated with hydrazine under anhydrous conditions to obtain 2-[¹²³I]-iodoisonicotinic acid hydrazide. The overall radiochemical yield was 69%. Biodistribution data of both radio-tracers in male Sprague-Dawley rats were collected. This is the first report of SPECT radiopharmaceuticals which may be useful for differential diagnosis of intracranial masses (tuberculoma vs glioma), and CNS tuberculosis in immunosuppressed subjects.     

Differential kinetics of [123I]β-CIT binding to dopamine and serotonin transporters

Iodine-123-labelled 3-(4-iodophenyl)tropane-2-carboxylic acid ([¹²³I]-CIT) labels both the dopamine transporter (DAT) and the serotonin transporter (5-HTT) and this ligand is able to clarify pathological changes in both dopaminergic and serotonergic systems. However, the differential kinetics of -CIT binding to DAT and 5-HTT has not been clarified fully. In this study we examined time-activity curves of [¹²³I]-CIT in individual regions in the rat brain. Using cerebellum as the reference region,k ₃ andk ₄ values were estimated by a two-compartment kinetic analysis. In the striatum, the kinetics was slowest among all brain areas. In this area specific binding reached its peak 4 h after the injection. In the hypothalamus, specific binding reached its peak 1 h after the injection and its amount did not change until 4 h after the injection. In the occipital cortex, the binding and washout of the ligand were fastest among all brain regions. Estimatedk ₃ values were 0.040±0.003 in the striatum, 0.019±0.002 in the hypothalamus and 0.082±0.011 in the occipital cortex (min^–t, mean ±SD). Estimatedk ₄ values were 0.0034±0.0005 in the striatum, 0.0071±0.0009 in the hypothalamus and 0.083±0.013 in the occipital cortex (min^–1, mean ±SD). Therefore binding kinetics of [¹²³I]-CIT in the region rich in DAT is apparently different from that in the region rich in 5-HTT. These results will provide fundamental data to image both DAT and 5-HTT in one series of examinations with [¹²³I]-CIT.     

No-carrier-added radiosynthesis of [123I]HIPDM: N,N,N′-trimethyl-N′-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3-propanediamine

The multi-millicurie production of the SPECT radiopharmaceutical N,N,N′-trimethyl-N′-(2-hydroxy-3-methyl-5-[¹²³I]iodobenzyl)-1,3-propanediamine ([¹²³I]HIPDM) in high specific activity is described. Using no-carrier-added electrophilic iododeprotonation reactions and HPLC purification, [¹²³I]HIPDM can be isolated in 70–76% radiochemical yield and specific activity >2000 Ci/mmol within an overall preparation time of 75 min. This methodology is readily adapted to the clinical setting, and eliminates the need for co-injection of macroscopic HIPDM in SPECT imaging procedures.     

High uptake of L-3-[123I]iodo-α-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[¹²³I]iodo-!-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n=10, r=0.87, P<0.05). Differences in IMT uptake in primaries (1.7ǂ.6, n=10) and in recurrent tumours (2.3ǂ.7, n=6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.     

Kinetics of 3-[123I]iodo-l-α-methyltyrosine transport in rat C6 glioma cells

3-[¹²³I]Iodo-l-α-methyltyrosine (¹²³I-IMT) is used for the diagnosis and monitoring of brain tumours by means of single-photon emission tomography (SPET). To date, little has been known about the system for the transport of ¹²³I-IMT into brain tumour cells. It is assumed that ¹²³I-IMT is transported by a specific carrier for large, neutral amino acids (L-system). In this study, rat C6 glioma cells were used to characterize the uptake system of ¹²³I-IMT and to investigate its precise kinetics. The time course of ¹²³I-IMT uptake into the cells was examined for a range of 1–60 min. ¹²³I-IMT uptake rates with varying concentrations of ¹²³I-IMT (2.5–50 μM) in the medium were quantified to assess the kinetic parameters of ¹²³I-IMT transport. Furthermore, competition of ¹²³I-IMT with other amino acids was investigated to identify the distinct transport systems involved in ¹²³I-IMT uptake. ¹²³I-IMT uptake into C6 glioma cells was linear for approximately 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of ¹²³I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K _m) of ¹²³I-IMT was 26.2±1.9 μM, and the maximum transport velocity (V _max) was 35.4±1.7 nmol/mg protein per 10 min. 77%±10% of ¹²³I-IMT transport was sodium independent and 23%±3% was sodium dependent. Competitive inhibition of ¹²³I-IMT uptake by 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, α-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major ¹²³I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B^0,+ (17%). Our results show that ¹²³I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B^0,+-system. The kinetic parameters of ¹²³I-IMT uptake are in the range of those of naturally occurring amino acids. Received 20 October 1998 and in revised form 25 May 1999     

Intra-individual comparison of p-[<Superscript>123</Superscript>I]-iodo-L-phenylalanine and L-3-[<Superscript>123</Superscript>I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

Objectives Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[¹²³I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[¹²³I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. Methods Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. Results Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. Conclusions IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. This work was supported by a grant from the “Deutsche Krebshilfe” (70-3024-He 1).     

头部外伤的123I－IMPSPECT──定量评价

头部外伤患者20例(平均年龄53.3±21.1岁)。均有脑震荡,经过2周以上住院治疗,神经症状稳定。既往无神经疾患,CT检查无异常者12例作为对照组(平均年龄57.9±9.3岁)。     

Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [123I]ß-CIT and high-resolution SPET

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriatal dopaminergic function in WD in relation to different courses and severity of the disease. Using high-resolution single-photon emission tomography (SPET) after administration of 2ß-carbomethoxy-3ß-(4[¹²³I]iodophenyl)tropane ([¹²³I]ß-CIT), striatal dopamine transporters (DAT) were imaged in 43 WD patients and a control group of ten subjects. From the SPET images, specific [¹²³I]ß-CIT binding ratios were obtained for the caudate heads, putamina and entire corpus striatum. In addition, to evaluate a putative dissociation between the caudate and putaminal [¹²³I]ß-CIT binding ratios, the ratio between these binding ratios was calculated (CA/PU ratio). The SPET data were compared with clinical data on the course of the disease (CD), the severity of neurological symptoms and the degree of hepatic alteration. Whereas the specific regional [¹²³I]ß-CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the control group (e.g. striatal ratios: 13.4Dž.0 vs 11.7DŽ.8), in patients with neurological CD the ratios were significantly reduced for all striatal substructures (P=0.003 after one-factor ANOVA). For the different subgroups a tendency was detected towards a stepwise decrease in the specific [¹²³I]ß-CIT binding ratios from pseudo-sclerosis CD (9.4DŽ.3), through pseudo-parkinsonian CD (9.1DŽ.1) to arrhythmic-hyperkinetic CD (8.5ǃ.6). However, these group differences reached significance only for the comparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was significantly higher in WD than in the control group (1.30ǂ.19 vs 1.11ǂ.08; P=0.003). Severity of neurological symptoms was significantly correlated with all specific regional [¹²³I]ß-CIT binding ratios (r=-0.49 to -0.57). For degree of liver alteration, significant correlations were obtained with the putaminal binding ratio (r=-0.37) and the CA/PU ratio (r=0.44). From these results is concluded that in WD the nigrostriatal dopaminergic function is compromised to varying extents. The degree of this presynaptic alteration of dopaminergic neurotransmission depends on the clinical course and severity of this copper deposition brain disorder and also varies in the different striatal substructures.     

Relationship between striatal [123I]β-CIT binding and four major clinical signs in Parkinson’s disease

We investigated the correlation between clinical severity and striatal [123I]-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65 +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V'3 (day 1)], and at 24 hours [V'3 (day 2)) after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p < 0.0012) was between putamenal V'3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V'3 (day 2) (r = -0.81, p < 0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression.     

Radioiododemercuration: a simple synthesis of 5-[123/125/127I]iodo-2′-deoxyuridine

Through the use of iododemercuration, 5-[^123/125I]iodo-2′-deoxyuridine was synthesized rapidly and with high radiochemical purity from 5-chloromercuri-2′-deoxyuridine. The synthesis of radioiodinated 2′-deoxyuridine was achieved in one step in the presence of Iodogen in 50% yield after isolation by reverse phase high performance column chromatography. The radiochemical purity was greater than 99%. The ease and rapidity of both preparation and isolation of no-carrier-added 5-[^123/125I]iodo-2′-deoxyuridine, as well as the absence of any starting material, suggests that radiohalodemercuration may be the method of choice for this and structurally similar compounds.     

Enhancement of [123I]β-CIT binding in the striatum with clomipramine: Is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [¹²³I]-CIT (RTI-55), in rat brain. Dose-dependent changes in [¹²³I]-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [¹²³I]-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region,k ₃ andk ₄ values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [¹²³I]-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed thatk ₃ in the striatum was increased by 55%. In conclusion, enhancement of [¹²³I]-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.     

123I闪烁照像及核磁共振显象对胸腔甲状腺肿的评价

胸骨后异位甲状腺,虽仅占所有纵膈肿物的10%,但诊断纵膈肿物时应给予注意。     

^123I—epidepride：多巴胺D2受体显像剂

＾１２３Ｉ－ｅｐｉｄｅｐｒｉｄｅ是一种较好的多巴胺Ｄ２受体ＳＰＣＥＴ显像剂，其亲和力高，亲脂性相对较低，适于纹状体和纹状体外造影，在垂体腺瘤显像中有较高的临床应用价值，并可预测一些垂体腺瘤对多巴胺治疗的反应。     

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Purpose Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinsons disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis.Methods The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [¹²³I]-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained.Results In the group of patients with APS, baseline [¹²³I]-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups.Conclusion [¹²³I]-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.