New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors.

Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.     

Alveolar epithelial permeability in patients with primary spontaneous pneumothorax as determined by Tc-99m DTPA aerosol scintigraphy

PURPOSE: Primary spontaneous pneumothorax (PSP) occurs subsequent to a disruption in the continuity of visceral pleura and escape of air into the pleural space. The cause of PSP is most often the rupture of subpleural blebs or bullae. It is usually difficult to detect evidence of pulmonary pathology. The purposes of the present study were (1) to investigate the changes of pulmonary alveolar epithelial permeability in patients with PSP as determined by Tc-99m DTPA aerosol lung scintigraphy, (2) to assess whether or not some differences exist between apical and basal parts of the lungs, and (3) to determine the relationship between the clearance rate of Tc-99m DTPA and the PFT results, the recurrence rate of PSP, and the percentage of pneumothorax in affected lung. MATERIAL AND METHODS: Thirteen PSP patients (two females, 11 males; mean age 32.5 +/- 11.8 years) with normal chest X-ray were studied. Thirteen healthy non-smoking volunteers (1 female, 12 males; mean age, 35.8 +/- 10 years) were selected as a control group. Tc-99m DTPA aerosol lung scintigraphy and PFT were performed in all patients and controls. Clearance rates (%/min) of Tc-99m DTPA aerosol in right and left lung field, and apical and basal parts of each lung were calculated from dynamic images for 15 min. RESULTS: There was no significant difference (p > 0.05) between patients and controls, or between apical and basal parts of each lung. No correlation was found between the clearance rate of Tc-99m DTPA and PFT results, the recurrence rate of PSP, or the percentage of pneumothorax. CONCLUSION: This study demonstrates that pulmonary epithelial permeability is not altered in PSP patients; the clearance rate of Tc-99m DTPA shows no difference between apical and basal parts of each lung.     

Cell surface expression of single chain antibodies with applications to imaging of gene expression in vivo

Imaging of gene expression in vivo has many potential uses for biomedical research and drug discovery, ranging from the study of gene regulation and cancer to the non-invasive assessment of gene therapies. To streamline the development of imaging marker gene technologies for nuclear medicine, we propose a new approach to the design of reporter/probe pairs wherein the reporter is a cell surface-expressed single chain antibody variable fragment that has been raised against a low molecular weight imaging probe with optimized pharmacokinetic properties. Proof of concept of the approach was achieved using a single chain antibody variable fragment that binds with high affinity to fluorescein and an imaging probe consisting of fluorescein isothiocyanate coupled to the chelator diethylene triamine penta-acetic acid labeled with the gamma-emitter ¹¹¹In. We demonstrate specific high-affinity binding of this probe to the cell surface-expressed reporter in vitro and assess the in vivo biodistribution of the probe both in wild-type mice and in mice harboring tumor xenografts expressing the reporter. Specific uptake of the probe by, and in vivo imaging of, tumors expressing the reporter are shown. Since ScFvs with high affinities can be raised to almost any protein or small molecule, the proposed methodology may offer a new flexibility in the design of imaging tracer/reporter pairs wherein both probe pharmacokinetics and binding affinities can be readily optimized.     

99Tcm-DTPA肾动态显像判断2型糖尿病肾小球功能的意义

为探讨99Tcm-DTPA肾动态显像判断2型糖尿病患者肾小球功能的临床价值,分析正常对照者18例、2型糖尿病患者62例行99Tcm-DTPA肾动态显像临床资料。2型糖尿病患者按WHO诊断确诊,将尿蛋白半定量测定结果分3组,获得总肾与分肾肾小球滤过率(GFR)。结果,①2型糖尿病各组总肾及分肾GFR均低于对照组;②总肾及分肾GFR与尿蛋白呈显著负相关,r分别为-0.562,-0.498,-0.524(P<0.01)。③62例2型糖尿病患者中有7例总肾GFR正常,而分肾GFR高于正常,有2例总肾与分肾均高于正常。表明用99Tcm-DTPA肾动态显像判断2型糖尿病患者肾小球功能有一定价值。     

Efficient lung scintigraphy

Lung scintigraphy is a first‐choice method to diagnose lung embolism. The clinical routine in most centres is a perfusion study complemented with a ventilation study when judged necessary. We describe a routine with ventilation scintigraphy preceding perfusion scintigraphy, which is completed within one hour. Furthermore, the data acquired allow the determination of lung clearance of the tracer ^99mTc‐DTPA (diethylene triamine penta‐acetate) used for the ventilation scintigraphy. An aerosol generator charged once a day with ^99mTc‐DTPA solution is used for all inhalations during the day. Inhalation is monitored with a counter and interrupted when the count rate corresponds to about 20 MBq. The ventilation imaging starts and ends with posterior projections. This allows calculation of lung clearance of ^99mTc‐DTPA. Perfusion scintigraphy is performed in a standard fashion with 100 MBq of ^99mTc‐MAA (macro‐aggregated albumin). The ventilation study was considered to give some diagnostic information in the majority of the patients. The clearance determination allows detection of inflammatory lung disease. The background activity caused by the ventilation study comprised only 13% of the activity in the perfusion scintigraphy and did not significantly interfere with interpretation of the perfusion scan. The cost for the investigation is low because of the rational system for aerosol administration and the short time for a complete study.     

Pulmonary absorption of instilled and inhaled DTPA in smokers

Summary. Pulmonary absorption of DTPA (diamine-triethylene-penta-acetic acid) has been widely adopted as an index of pulmonary epithelial permeability. The aim of this study was to analyse:

• 1 if measurements of pulmonary absorption are influenced by the amount of fluid being administered to the lungs together with the DTPA; and
• 2 if all DTPA administered to the lungs is equally accessible for pulmonary absorption.

To this end DTPA was instilled into a lung segment of six smokers in association with a bronchoscopy. In six other subjects (five smokers and one ex-smoker) the DTPA was inhaled as an aerosol. Pulmonary absorption of DTPA was calculated from the plasma DTPA content, as determined for 4–10 h after the administration of the DTPA. We found that the mean transit time for the absorption of instilled DTPA, i(L), across the pulmonary membranes was significantly (P<0·05) longer (median 1498 min, range 955–2636 min) than the fi(L) of the absorption of the inhaled DTPA (median 131 min, range 44–512 min). Pulmonary clearance of the inhaled aerosolized DTPA tended to be faster when determined by external detection for 4 h, than when estimated from plasma samples, suggesting that not all pulmonary DTPA may be equally accessible for absorption from the pulmonary lining fluids. We conclude that pulmonary absorption of DTPA is influenced by the volume of fluid being administered to the lungs in association with the measurements. Not all pulmonary DTPA, however, is equally accessible for absorption, rendering external detection of pulmonary clearance of DTPA sensitive to a variety of factors other than pulmonary absorption.     

(99m)Tc-EC与(99m)Tc-DTPA肾显像特征的比较

目的探讨~(99m)Tc-EC与~(99m)Tc-DTPA肾显像结果的差异。方法共分为3组,即肾功能正常组(15人)、肾功能轻～中度受损组(37人,53侧病变肾)和肾功能重～极重度受损组(27,41侧病变肾)。用常规剂量的~(99m)Tc-EC和99mTc-DTPA分次进行肾显像,得出肾血流功能图像、肾图,并求出肾放射性摄取高峰时间(Tmax)、半排时间(T1/2)、相对肾脏指数(RI)、有效肾血浆流量(ERPF)和肾小球滤过率(GFR)。结果①在正常组中,99mTc-DTPA的T1/2要大于99mTc-EC,差异显著(P<0.0001),Tmax和RI差异不显著。②在肾功能轻～中度受损组中,99mTc-DTPA的Tmax要小于99mTc-EC,差异显著(P<0.05),T1/2和RI差异不显著。③在肾功能重～极重度受损组中,99mTc-DTPA的RI要小于99mTc-EC,差异显著(P<0.0001),Tmax差异不显著。④肾功能受损时,99mTc-DTPA的功能图像和肾图差于99mTc-EC,肾功能受损越重,差别越明显。结论①在同一生理或病理情况下99mTc-EC和99mTc-DTPA的肾显像结果有差异,99mTc-EC肾显像的图像质量优于99mTc-DTPA。②肾显像时,如不要求得出GFR,肾显像剂99mTc-EC为优选。     

瘤样炎性脱髓鞘病MRI的临床意义

目的分析瘤样炎性脱髓鞘病(TIDD)临床、影像与病理特点,探讨磁共振(MRI)检查对TIDD的诊断价值。方法对39例TIDD患者进行头颅、脊髓CT和MRI扫描,并分析临床和影像学特点。结果病灶在头颅CT均为低密度,常规MRI扫描呈T1WI低信号、T2WI高信号,T1WI增强扫描44%可见"开环征",发病早期DWI可见高信号,FLAIR较T1WI及T2WI更清晰显示病灶及其范围。结论 DWI能发现TIDD早期病变,FLAIR较常规T1WI、T2WI敏感,"开环征"是磁共振诊断TIDD的重要辅助依据。     

Preparation and preliminary biological evaluation of 177Lu‐labeled GluDTPA‐cyclo(RGDfK) for integrin ανβ3 receptor‐positive tumor targeting

Integrin α_νβ₃ is a receptor and is highly expressed on activated and proliferating endothelial cells during the growth and metastasis of solid tumors but not on resting endothelial cells and normal organs. Because RGD peptide binds to integrin α_νβ₃ receptor, a variety of radiolabeled RGD peptides have been evaluated for non‐invasive imaging of integrin α_νβ₃‐positive tumors. In an attempt to develop RGD‐based radiopharmaceuticals, a novel GluDTPA‐cyclo arginine‐glycine‐aspartic acid‐d ‐phenylalanine‐lysine (GluDTPA‐cycloRGDfK) was simply synthesized and radiolabeled with ¹⁷⁷Lu. Also, tumor targeting and retention of the radiolabeled complex were evaluated in U87MG glioma‐bearing mice. The ¹⁷⁷Lu‐labeled GluDTPA‐cyclo(RGDfK) was formulated with a high radiolabeling yield (>98%) under mild condition, and the radiochemical purity was sustained in both saline and serum for over 4 days at 37°C. The radiolabeled compounds were rapidly cleared from the blood pool and non‐target tissue. Tumor‐to‐blood ratio was 12.09 at 2 h post injection and increased to 134.67 at 24 h, while tumor to liver ratio was 2.01 at 24 h similar to that of 2 h. Though it is inappropriate for targeted therapy due to its low uptake in tumor (~ 1 %ID/g), the acceptable results on radiochemistry and biodistribution propose to take a further assessment for non‐invasive imaging and detection of integrin α_νβ₃‐positive tumors by applying diagnostic radionuclides. Copyright © 2011 John Wiley & Sons, Ltd.     

Simple provocative maneuvers in renal transplant scintigraphy for detecting urine leak

Urine leak in the early postoperative period following renal transplantation is a serious complication requiring early identification and aggressive intervention, which significantly reduces the morbidity and mortality. Renal transplant scintigraphy is a noninvasive method to evaluate the perfusion and function of a transplanted kidney and urinary drainage including urine leak. Here, we reported two cases in which the standard transplant renogram failed to demonstrate urine leak. The cases were referred for a diethylenetriaminepentaacetic acid renogram following the transplantation to evaluate the cause of symptoms or elevated serum creatinine level. In both the cases, urine leak was successfully detected following simple maneuvers such as diuretic administration or Foley catheter irrigation. Renal transplant scintigraphy is an effective and safe technique and the use of these simple maneuvers can enhance the diagnostic sensitivity of the transplant renogram in the detection of urine leak.