Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.     

Graduated compression stockings in the prevention of deep vein thrombosis in patients with acute myocardial infarction

Venous volume (venous capacity) of the calf is low in patientswith acute myocardial infarction, who also have a high riskof deep vein thrombosis (DVT). The effect of graduated compressionstockings on the venous volume and on the incidence of DVT wastherefore studied in 80 patients aged 70 years and above withacute myocardial infarction. Graduated compression stockingswere randomly fitted to one leg, the other serving as a control,after which the venous volume was measured by strain gauge plethysmography.The incidence of DVT was measured by the ¹²⁵I fibrinogen uptaketest. Venous volume was significantly higher in legs treatedwith graduated compression stockings compared to control legs.DVT developed in eight control legs but not in any leg treatedwith graduated compression stockings (P = 0.003). DVT was alsosignificantly more frequent in women compared to men and themajority of DVT developed in legs with very low venous volumevalues.     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.     

[125I] N6-p-hydroxyphenylisopropyladenosine,a new ligand for Ri adenosine receptors

Summary N⁶-p-Hydroxyphenylisopropyladenosine (HPIA) has been labelled with carrier-free Na[¹²⁵I] to very high specific activity (2,175 Ci/mmol) and used as an agonist ligand to characterize R_i adenosine receptors in rat cerebral cortex membranes. The binding is saturable, reversible, stereospecific and dependent on protein concentration. The specific binding at 37°C was of high affinity with an equilibrium dissociation constant K_D of 0.48 nmol/l and was saturable with 0.23 pmol of [¹²⁵I]HPIA per mg of protein. The rate constant of association, k₁, was 3.25×10⁸ l mol^–1 min^–1 and that of dissociation, k₂, 0.0110 min^–1 yielding a t_1/2 of 63 min. In competition experiments the (–)isomer of N⁶-phenylisopropyladenosine (PIA) was 16-fold more potent than the (+)isomer in competing for the binding sites. Specific binding was most effectively displaced by N⁶-cyclohexyladenosine (CHA, k_i=0.26 nmol/l), (–)PIA (k_i=0.33 nmol/l) and HPIA (k_i=0.52 nmol/l), whereas 5-N-ethylcarboxamidoadenosine (NECA, k_i-1.42 nmol/l) was less effective. The methylxanthines 3-isobutyl-1-methylxanthine (IBMX), theophylline and caffeine which have been classified as adenosine antagonists had k_i values between 5–34 mol/l. Binding of [¹²⁵I]HPIA was regulated by guanine nucleotides and divalent cations. The results indicate that [¹²⁵I]HPIA labels R_i adenosine receptors in rat brain membranes.     

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.     

对子宫腺肌病患者血清CA125及EMAb的临床评价

目的：探讨血清CA125及子宫内膜抗体（EMAb)测定，对子宫腺肌病的诊断及疗效评估的临床价值。方法：经术后病理学检查确诊子宫腺肌病患者63例和子宫肌瘤患者45例，均于术前及术后测定两组血清CA125水平和EMAb。结果：子宫腺肌病组术前血清CA125平均水平及EMAb阳性率均高于子宫肌瘤组，两者相比差异有显著性（P＜0．001及P＜0．01）。联合测定血清CA125水平和EMAb，以两者均阳性为诊断标准，诊断子宫腺肌病的敏感性为54．63％，特异性为100％。子宫腺肌病组术后血清CA125水平和EMAb阳性率均较术前下降，差异有显著性（P＜0．01及P＜0．05）。结论：测定血清CA125及EMAb对子宫腺肌病有较好的辅助诊断价值，联合检测更能提高诊断的正确性，并可作为评价子宫腺肌病疗效的敏感指标。     

血清CA125检测在子宫内膜癌中的价值

目的探讨血清CA125在子宫内膜癌中的价值.方法选取1992年3月～2002年3月在北京大学第一附属医院、北京大学人民医院住院经手术治疗的子宫内膜癌患者141例,术前及随访中用放射免疫法测定血清CA125水平,CA125≥35 U/ml 为阳性结果.对其中14例行子宫内膜癌组织CA125免疫组化方法检测.收集患者的临床病理资料,分析CA125与这些资料的关系以及复发患者复发前后CA125变化.结果 CA125免疫组化检测14例均呈阳性,阳性细胞着色率与血清CA125之间无明显相关.141例患者术前血清CA125阳性32例(22.7%), Ⅰ、Ⅱ、Ⅲ和Ⅳ期患者血清CA125阳性(阳性率)分别为11例(12.1%)、6例(31.6%)、12例(46.2%)和3例(60.0%). 血清CA125阳性率随子宫内膜癌期别的增加而升高.深肌层浸润、宫颈受累、附件转移、腹腔洗液细胞学阳性、盆腔淋巴结转移及宫内肿瘤病灶≥2 cm者,血清CA125阳性率增加.随访中13例复发,其中9例术前血清CA125＞35 U/ml者复发时均伴血清CA125水平升高,而另4例术前血清CA125正常者,复发后血清CA125水平仍正常.结论子宫内膜癌患者术前血清CA125的测量有助于了解肿瘤的侵犯范围.术前血清CA125水平异常的子宫内膜癌患者,术后定期复查血清CA125水平,将有助于子宫内膜癌病情的监测.     

南瓜子的研究进展

本文对近年来有关南瓜子的化学成分、药理作用、临床应用等方面的研究进展作一概述。其化学成分主要含有脂肪酸，植物甾醇，氨基酸，维生素和矿物质等。药理研究表明有驱除寄生虫，降低LDL胆固醇，抗炎，缓解高血压，减少膀胱和尿道张力等作用，毒性很小。临床报道用于治疗绦虫病，血吸虫病，前列腺炎，前列腺增生，改善膀胱刺激征，防止尿道结石形成等。     

[125I], [127I]‐and [14C]‐Labelling of the GLP‐1‐(7‐37) derivative NN2211

Arg³⁴Lys²⁶(N^ε‐(γ‐L ‐glutamyl(N^α‐palmitoyl)))‐GLP‐1(7‐37) (NN2211) is currently in development as a diabetes type 2 drug. The fatty acid attached to the GLP‐1(7‐37) ensures a long and controlled duration of action. The synthesis of [¹²⁵I]NN2211, [¹²⁷I]NN2211 and [¹⁴C]NN2211 used for preclinical ADME studies are described. NN2211 was iodinated using the lactoperoxidase/hydrogen peroxide method, and [¹⁴C]NN2211 was synthesized in 4 steps by two routes both starting from an α‐protected [U‐¹⁴C]glutamic acid. Copyright © 2003 John Wiley & Sons, Ltd.