Splenic, hepatic, renal and pulmonary clearance dysfunction associated with high-energy X-rays.

PURPOSE: To verify the high-energy X-rays effects on the blood clearance of colloidal particles by the spleen, liver, kidneys, and lungs. MATERIALS AND METHODS: Seventeen male Wistar rats were distributed into three groups. Group 1 (n = 5) - control - non-irradiated animals, group 2 (n = 6) - irradiated animals studied 24 h after irradiation, and group 3 (n = 6) - irradiated animals studied 48 h after irradiation. The animals were anesthetized and irradiated with a non-fractionated 8 Gy dose in the abdominal region divided into two parallel and opposite fields, 4 Gy was given to the anteroposterior and 4 Gy to the posteroanterior. This high dose of high-energy X-rays causes extensive cell killing, tissue disorganization and break down cell to cell communication. According to the groups, 50 µCi of technetium-phytate were injected into the right internal jugular vein. After 30 minutes, the liver, spleen, kidneys, and lungs were removed. The clot was harvested from the abdominal cavity two minutes after the sectioning of the abdominal aorta and cava vein. The organs and clot were placed into plastic flasks to be weighed and studied for the emission of radioactivity in a gamma radiation detector. The uptake function of each organ was calculated based on the count of gamma rays emitted per minute and normalized with the organ mass, having as a reference the radioactivity count of a standard sample. The arithmetic mean of each organ uptake was calculated and compared among the groups. RESULTS: After irradiation, the spleen uptake of colloidal radiopharmaceutical was greater, while the hepatic, renal, and pulmonary uptake were lower. The renal uptake decreased slower than the hepatic and pulmonary uptake. CONCLUSIONS: A single high dose of high-energy X-rays enhances the splenic clearance function, while it reduces the hepatic, renal, and pulmonary clearance until 48 h after irradiation, with a rapid deterioration of the hepatic and pulmonary uptake function.

Evolving role of radiolabeled particles in detecting infection and inflammation, preliminary data with 99mTc-phytate in rats.

PURPOSE: The aim of this study was to evaluate the ability of phytate radiolabeled with technetium-99m (Tc-phytate) to identify inflammatory processes. MATERIALS AND METHODS: Radiolabeling efficiency analyses were carried out by thin-layer chromatography on silica gel strips, yielding a radiochemical purity of 92%. In addition, the partition coefficient of Tc-phytate, obtained in a mixture of n-octanol/water (1 : 1), showed hydrophilic features of the radiopharmaceutical. After Tc-phytate was administered into the tail vein of healthy and inflammation focus-bearing rats, induced, in the right tight, by zymosan suspension at 5% (w/v), blood clearance evaluation was performed and showed a short plasma half-life (2.7 min). In the inflammation focus-bearing rats, Tc-phytate scintigraphic images were obtained at 2, 4, and 8 h after radiotracer injection. RESULTS: A significant radiopharmaceutical uptake was found in mononuclear phagocyte system organs (liver and spleen) and in the inflammation focus (compared with contralateral muscle). Histopathological analysis showed an intense mononuclear infiltration in the inflamed muscle, suggesting that macrophages may be responsible for the greater radiotracer uptake in the inflamed site. Furthermore, the target-to-nontarget ratio (%ID/g of inflamed muscle-to-%ID/g of control muscle ratio) obtained by scintigraphic images performed at 2 h after the radiotracer injection was 10.24±3.49, remaining without any significant difference at 4 and 8 h. CONCLUSION: Inflammation focus was evident in the scintigraphic images from 2 to 8 h after Tc-phytate administration, suggesting that this radiopharmaceutical could be a potential alternative to identify inflamed regions.

99mTc-phytate as a diagnostic probe for assessing inflammatory reaction in malignant tumors.

OBJECTIVE: Once administered intravenously, technetium-99m (99mTc)-labeled phytate binds to calcium in the serum and behaves as a nanoparticle. On the basis of the high permeability of the tumor vasculature, 99mTc-phytate is expected to leak and accumulate specifically in inflammatory cells. The aim of this study was to evaluate the potential of 99mTc-phytate in assessing the degree of inflammation in Ehrlich solid tumors in mice. MATERIALS AND METHODS: 99mTc-phytate was prepared by adding pertechnetate to a solution containing phytic acid and stannous chloride. The blood half-life of this particle following intravenous injection was determined using blood samples from healthy animals, whereas its size was measured by photon correlation spectroscopy. Scintigraphic imaging and biodistribution studies were carried out in tumor-bearing mice at 30 min and 2 h after injection. RESULTS: The average size of the particles was in the range of 200 nm, suggesting that they are capable of passively passing through fenestrations in tumor vessels, which are 200-2000 nm in size. The blood half-life for 99mTc-phytate was found to be 2.1 min, a result that is in agreement with previous studies. Data from tumor-bearing mice showed high tumor uptake at 2 h after 99mTc-phytate administration. As a result, a high tumor-to-muscle ratio was achieved (T/M = 25.9 ± 7.54). CONCLUSION: These findings indicate that 99mTc-sodium phytate has promising properties for identifying the type of tumor. This approach will have significant implications for characterizing tumor biology and treatment of malignant lesions.

Leukocyte-technetium-99m uptake in Crohn's disease: does it show subclinical disease?

AIM: To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy. METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes. RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% +/- 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20). CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.

Tissue distribution evaluation of stealth pH-sensitive liposomal cisplatin versus free cisplatin in Ehrlich tumor-bearing mice.

Multidrug resistance and drug toxicity represent major obstacles to cancer chemotherapy. Drug delivery systems, such as liposomes, offer improved chemical stability of encapsulated drugs, enhanced accumulation in tumors and decreased toxicity. The aim of this study was to evaluate the tissue distribution of stealth pH-sensitive liposomes containing cisplatin (SpHL-CDDP), compared with free cisplatin (CDDP), in solid Ehrlich tumor-bearing mice. After administering a 6 mg/kg single intravenous bolus injection of either free radiolabeled cisplatin or SpHL containing radiolabeled cisplatin, blood and tissues were analyzed for cisplatin content by determining radioactivity using an automatic scintillation apparatus. The area under the CDDP concentration-time curve (AUC) obtained for blood after SpHL-CDDP administration was 2.1 fold larger when compared with free CDDP treatment. The longer circulation of SpHL-CDDP led to a higher tumor AUC, and the determination of the ratio between AUC in each tissue and that in blood (Kp) showed a higher accumulation of CDDP in SpHL-CDDP administrated tumors. The SpHL-CDDP was also significantly uptaken by the liver and spleen. The distribution of SpHL-CDDP in these organs was extensive, revealing a high extravasation of CDDP to the tissues. The SpHL-CDDP kidney uptake was also greater than that of free CDDP; however, the Kp value found was lower. This indicates that the SpHL-CDDP led to a reduction of CDDP retention by renal tissue. Thus, these results indicate that the SpHL-CDDP may indeed be useful in alleviating renal damage induced by CDDP and thus represents a promising delivery system for cancer treatment through CDDP.