红细胞生成素:一种新的神经保护剂

红细胞生成素(erythropoietin, EPO)作为细胞因子超家族中的一员,在体内和体外均显示出显著的神经保护功能.该作用可能主要通过抗凋亡、抗氧化、促进血管再生等机制实现.大剂量EPO能通过血脑屏障并发挥神经保护作用.EPO经人工改造后可消除造血系统不良反应.EPO的临床应用有望对神经系统疾病的预后及治疗提供新的思路.     

Radiographic demonstration of a toxic agent

The abdominal radiographs obtained on a young man attempting suicide by stabbing revealed an unusual opacity in the true pelvis, confirmed as being due to unsuspected carbon tetrachloride ingestion. This is the first known radiologic demonstration of oral ingestion of a rapidly acting toxic substance.     

Iodothiouracil as a melanoma localizing agent

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.     

Gd-DTPA as a contrast agent in CT

An evaluation was done of the effect of gadolinium diethylenetriaminepentaacetic acid (DTPA) on computed tomographic (CT) studies performed after magnetic resonance (MR) imaging. CT scans of two solutions of Gd-DTPA demonstrated substantial attenuation. In two patients who underwent CT after Gd-DTPA-enhanced MR imaging, the high attenuation of concentrated Gd-DTPA was seen in the urinary bladder and renal collecting system. However, in the concentration presently used in MR imaging, Gd-DTPA results in only minor enhancement of renal cortex.     

Gadolinium as a contrast agent for NMR

Gadolinium chloride (GdCl3) was studied as a contrast agent for nuclear magnetic resonance. This rare-earth element dramatically alters proton resonance (paramagnetic moment = 10.8 Bohr magnetons). Acute toxicity was determined by intravenous injections in mice; mean lethal dose was 100-200 mg of GdCl3 . 6 H2O/kg. Changes in T1 of plasma, kidney, liver, and brain of mice and rats were measured after intravenous injections of GdCl3 solution at a concentration of 60 mg gadolinium metal/kg. The apparatus used was a Wh 270 Brucker with a field of 63 kG. The T1 was found to be significantly decreased in plasma, kidney, and liver.     

105Rh as a potential radiotherapeutic agent

The production of 35.5-h ¹⁰⁵Rh (560- and 250-keV betas) by neutron activation of ¹⁰⁴Ru followed by beta decay of 4.4-h ¹⁰⁵Ru is discussed. A simple procedure for producing ¹⁰⁵Rh in 10–100 mCi quantities at specific activities of 700–10,000 Ci/mmol is described.     

Dextran magnetite as a liver contrast agent

The superparamagnetic particle dextran magnetite was studied as a liver tumor contrast agent for magnetic resonance imaging (MRI). The effects of dextran magnetite on the longitudinal (T1) and transverse (T2) relaxation times in liver, spleen, and an implanted rat liver tumor were measured at 0.47 T (IBM/Bruker PC-20 relaxometer) over the dose range of 23 to 69 mumol Fe/kg. Dextran magnetite substantially reduced the T2 of the liver and spleen, but not of the tumor, thereby providing a basis for improved tumor imaging. The T1 of the tumor was not affected following injection of dextran magnetite in the dose range studied, while the spleen T1 was reduced substantially more than the T1 of the liver. Histological studies using the iron reaction for Prussian blue clearly showed dextran magnetite in the liver and spleen, but not in the tumor. While dextran magnetite was sequestered in macrophages in both liver and spleen, the distribution in the liver was more diffuse (70 microns average particle separation) than that in the spleen (25 microns separation). The lack of a T1 effect in the liver is consistent with the fact that a majority of the water in the tissue cannot diffuse to the relaxational centers on the time scale of the liver's intrinsic T1 (280 ms). In the spleen, however, the dextran magnetite is more densely packed in the red pulp allowing a significant fraction of the water to be relaxed by a T1 mechanism. Spin-echo images of the implanted tumor (mammary adenocarcinoma. R3230AC) in the livers of Fischer 344 rats were obtained at 0.50 T (Siemens Magnetom). The tumor-to-liver contrast was improved for both T1 and T2-weighted spin-echo images after intravenous injection of the dextran magnetite contrast agent. The contrast determined from these images agreed with that predicted by the measured T1 and the T2 (Hahn spin-echo) values. In addition, gradient-echo T2-weighted images with good contrast were obtained in a much shorter imaging time than was needed for T2-weighted spin-echo images. These results demonstrate that the MRI contrast enhancement observed with dextran magnetite is based on its selective uptake and distribution in the macrophages in the liver and spleen and that this agent has substantial potential as a superparamagnetic MR contrast agent.     

Thallium-201 as a myocardial imaging agent

The field of myocardial perfusion imaging has made many advances but still is in its infancy. The limitations in the technology at this time include limited instrument resolution of 6-9 mm, intrinsic at the energy of the mercury x-ray; significant Rayleigh scatter, which is particularly distrubing because this scatter cannot be removed by pulse-height analysis; and an effective half-life of thallium in the myocardium, which makes repeated imaging over a short period of time very difficult. Although hopes for the development of a technetium-labeled myocardial imaging tracer have burnt brightly, no new agents are presently in sight. Resolution with a technetium-labeled tracer would almost double that of thallium, and the dose that could be administered to the patient would increase by at least a factor of 4. The effective half-life of the tracer in the myocardium would permit multiple images to be obtained at least in the same day. Even with the limitations of the current techniques, however, myocardial perfusion imaging can make a real contribution to the care of the patients with heart disease. Thallium is now produced commercially and reasonably easily obtained. Extraction of thallium by the myocardium is probably somewhat, but not exactly, analogous to potassium. The tracer has major applications in defining shape and size of the heart, thickness of muscle, and especially myocardial ischemia and infarction. This review is aimed at providing a current perspective of these uses.     

Unintentional intra-arterial injection of a bone-imaging agent

The inadvertent intra-arterial injection of a dose of Tc-99m-MDP is reported. Limited quantitative studies were done on the distribution pattern. More extensive investigations of cases of this type may yield useful data on the behavior of radiopharmaceuticals.     

99mTc-HIDA,a gallbladder imaging agent

The molecule N-(2,6-dimethyl-phenyl-carbamoyl-methyl)-iminodiacetic acid (HIDA), capable of chelating reduced ^99mTc, was synthesized, characterized, labeled with ^99mTc, and studied in experimental animals.The results indicated that the new ^99mTc-radiopharmaceutical is rapidly cleared from the blood to the liver, then rapidly removed to the gallbladder and excreted into the duodenum through the common bile duct.A comparative kinetic study of ^99mTc-HIDA and ¹³¹I-Rose Bengal performed in rabbits demonstrated that both radiopharmaceuticals had a similar blood clearance rate, but cleared at a different rate from liver to gallbladder. ^99mTc-HIDA showed a faster accumulation in the gallbladder than ¹³¹I-Rose Bengal.These findings, combined with the advantage of the low acute toxicity of HIDA, were promising enough to encourage a further evaluation and clinical investigation of this new Tc-99m hepatobiliary agent.     

Venography with carbon dioxide as a contrast agent

Purpose The purpose of this study was to evaluate the feasibility, safety, and potential role of carbon dioxide (CO₂) as a contrast agent for venography.Methods Consecutive patients with contraindications to iodinated contrast agents or with unsatisfactory iodinated contrast studies underwent CO₂ digital subtraction venography. The images were rated by three experienced angiographers. Image quality and complications were assessed.Results Over a 14-month period, 66 vein segments were studied in 21 patients. There was good correlation between experienced angiographers on CO₂ image quality (R_i = 0.80) and good agreement on diagnosis (k = 0.62). In 91% of the vein segments evaluated with CO₂ there was interobserver agreement on the diagnosis. Upper extremity veins were adequately imaged with CO₂ alone in all (6/6) patients with contraindications to iodinated contrast. Following suboptimal iodinated contrast studies in six patients, CO₂ produced significantly better quality upper extremity central vein images (p < 0.05). Pain following injection into peripheral veins was the only CO₂-related complication. Inferior vena cava (IVC) filters were successfully deployed with CO₂ alone in 78% (7/9) of patients; two required iodinated contrast.Conclusion Based upon initial experience, CO₂ venography can be recommended in patients with contraindications to iodinated contrast or unsatisfactory iodinated contrast studies.Presented before the Annual Meeting and Postgraduate Course, Cardiovascular and Interventional Radiological Society of Europe, June 7, 1994, Aghia Pelaghia, Crete, Greece.