Abstract  Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc) is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT) due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl(2)) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl(2) were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl(2) 500 μg/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay) and 36 h after, for micronucleus test. The data showed that both SnCl(2) and 99mTc-MDP-induced deoxyribonucleic acid (DNA) strand breaks in rat total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl(2) in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

Abstract  The pituitary TSH cell structure of middle-aged (14-month-old) female Wistar rats chronically treated with estradiol dipropionate (EDP), calcium glucoheptonate (Ca) or with the combination of both was studied. TSH-producing cells were examined in the pituitary pars distalis using rabbit anti-rat beta-thyrotropin (TSH) serum and peroxidase-antiperoxidase immunohistochemistry. A stereological method for the determination of morphometric changes of the volume of TSH cells and nuclei as well as of their number and relative volume densities was used. All examined morphometric parameters in treated animals showed a significant decrease in comparison with immunoreactive TSH cells of the controls; the most significant decrease was observed in EDP-treated rats. These results together with structural features of immunoreactive TSH cells in the pituitary of middle-aged rats after chronic application of EDP or Ca indicate that both compounds inhibit these cells.

Abstract  Foliar calcium applications are used in many fruiting crops to minimize disease and physiological disorders. In blueberry (Vaccinium spp), it is used to improve fruit firmness with varying success. Two applications of foliar calcium applied to rabbiteye blueberry (V. virgatum Aiton) cvs. Alapaha and Powderblue as calcium nitrate [Ca(NO3)(2)], neutralized calcium carbonate (CaCO3), and chelated calcium (calcium glucoheptonate, C-14 H-26 CaO16) were made at the label rate of 2.3 L. ha(-1) applied in a volume of 935.3 L. ha(-1) (697 ppm, 108 ppm, and 604 ppm Ca per application, respectively). The applications were made at 30 and 15 days preharvest in 2013 and 2014. Fruit were hand harvested at 40% ripe and evaluated for berry weight, color, firmness, soluble solids, and acidity. In 2013, fruit were stored at 1 degrees C with 85% relative humidity and evaluated again at 7 and 15 days. In 2014, fruit and tissue samples were evaluated for Ca concentration. In 2013, 'Powderblue' had a 5% increase in firmness from the CaCO3 treatment when compared to control fruit. The chelated calcium treatment significantly increased fruit weight by 12% compared to the control for 'Alapaha'. Fruit firmness increased 5% and fruit weight decreased 10% for the Ca(NO3)(2) treatment compared to control for 'Alapaha' fruit sampled after 2 weeks of storage. In 2014, none of the treatments significantly increased fruit firmness or berry calcium concentration. For 'Powderblue' in 2014, all treatments significantly decreased firmness. Leaf Ca concentration was increased by 18% for 'Alapaha' and decreased by 26% for 'Powderblue' when comparing the chelated calcium treatment to non-treated leaves.

Abstract  Molecular imaging has witnessed a tremendous change over the last decade. Growing interest and emphasis are placed on this specialized technology represented by developing new scanners, pharmaceutical drugs, diagnostic agents, new therapeutic regimens, and ultimately, significant improvement of patient health care. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. Moreover, the last section covers several application, of μ SPECT imaging in many areas of disease detection and diagnosis.

Abstract  To investigate the feasibility of using human major histocompatibility complex class I chain-related A (MICA) as a target for tumor imaging diagnosis, 10C6, a monoclonal antibody (mAb) that specifically recognizes MICA in vitro, was labeled with (99m)Tc (technetium) and administered into mice bearing MICA-positive human ovarian epithelial carcinoma line SKOV3. Measurement of organ-specific radioactivity showed that tumor accumulated radioactivity continuously, while the uptake in the other organs decreased over time. Scintigram showed that the tumor became clearly visible at 24h post-injection of radio-labeled 10C6 mAb. These results suggest that MICA is a promising target for tumor imaging and mAb 10C6 may be used clinically for early tumor diagnosis.

Abstract  Radioimmunotherapy (RIT) is currently being considered for the treatment of solid tumors. Although results have been encouraging for pretargeted 131I RIT with the affinity enhancement system (AES), the radionuclide used is not optimal because of its long half-life, strong gamma emission, poor specific activity, and low beta particle energy. 188Re, though unsuitable for direct antibody labeling, could be used with the AES two-step targeting technique. The purpose of this study was to compare the distribution and dosimetry of a bivalent hapten labeled with 188Re or 125I. For dosimetry calculations and biodistribution data, 125I was substituted for 131I. After preliminary injection of a bispecific anticarcinoembryonic antigen (CEA) or antihapten antibody (Bs-mAb F6-679), AG 8.1 or AG 8.0 hapten radiolabeled with 188Re or 125I was injected into a nude mouse model grafted subcutaneously with a human colon carcinoma cell line (LS-174-T) expressing CEA. A dosimetry study was performed for each animal from the concentration of radioactivity in tumor and different tissues. Radiolabeling of AG 8.1 with 125I afforded a 40% yield with a specific activity of 11.1 MBq/nmol after purification. Radiolabeling of AG 8.0 with 188Re afforded a 72% yield with a specific activity of 31.82 MBq/nmol. In all experiments, the percentage of tumor uptake of 125I-AG 8.1 was always significantly greater than that of 188Re-AG 8.0. The corresponding tumor-to-tissue ratios reflected uptake values. The least favorable tumor-to-normal tissue ratios in the dosimetry study were 8.1 and 8.5 for 131I (tumor-to-blood ratio and tumor-to-kidney ratio, respectively) and 2.3 for 188Re (tumor-to-intestine ratio). This study indicates that 188Re can be used for radiolabeling of hapten in two-step radioimmunotherapy protocols with the AES technique. 188Re has a greater range than 131I, which should allow the treatment of solid tumors around 1 cm in diameter. Although the method used for hapten radiolabeling did not provide optimal tumor uptake, the use of a bifunctional chelating agent associated with AG 8.1 should solve this problem.

Abstract  The exposure of anionic phospholipids is a near-universal molecular signature for cell death. Based on our prior finding that the ^sup 99m^Tc-labeled C2A domain of synaptotagmin I accumulates intensely in the area at risk, this study quantitatively characterized the temporal and spatial distribution of the radiotracer in a rat model of myocardial ischemia and reperfusion. Methods: Myocardial ischemia and reperfusion were induced by occlusion of the left anterior descending coronary artery in rats. The temporal uptake of the labeled fusion protein of C2A and glutathione-s-transferase (C2A-GST) in the area at risk was investigated by intravenously injecting the radiotracer at 0, 1, 3, 6, and 24 h after reperfusion, and the radioactivity uptake was quantified by γ-counting of infarcted and ischemic noninfarcted cardiac tissues. Alternatively, the radiotracer was injected at 2 h after reperfusion, and the uptake was measured at 1, 3, 6, and 24 h after injection. In vivo planar imaging was performed on a γ-camera using a parallel-hole collimator. The distribution of radioactivity was qualitatively examined by autoradiography. The relationship between the uptake of the radiotracer in the area at risk and the ischemic duration was examined by γ-counting. Results: Temporally, the radioactivity uptake in the area at risk maximized when the radiotracer was injected before 3 h after reperfusion. Injections at 6 and 24 h after reperfusion resulted in a 30% and 50% reduction in uptake, respectively. However, when the injection was done early (2 h after reperfusion), the tracer was retained in the area at risk with little washout for at least 24 h. Spatially prominent hot-spot uptake was seen in all cases of planar imaging. In autoradiography, the distribution of radioactivity predominantly coregistered with the infarcted regions. This distribution profile was confirmed by direct γ-counting. In addition, the absolute radiotracer uptake in the infarcted and ischemic noninfarcted tissues, in terms of percentage injected dose per gram, was independent of the ischemic duration. Conclusion: ^sup 99m^Tc-C2A-GST has an uptake profile in the area at risk that is appropriate for imaging cardiac cell death in the acute phase. [PUBLICATION ABSTRACT] The exposure of anionic phospholipids is a near-universal molecular signature for cell death. Based on our prior finding that the (99m)Tc-labeled C2A domain of synaptotagmin I accumulates intensely in the area at risk, this study quantitatively characterized the temporal and spatial distribution of the radiotracer in a rat model of myocardial ischemia and reperfusion. Myocardial ischemia and reperfusion were induced by occlusion of the left anterior descending coronary artery in rats. The temporal uptake of the labeled fusion protein of C2A and glutathione-s-transferase (C2A-GST) in the area at risk was investigated by intravenously injecting the radiotracer at 0, 1, 3, 6, and 24 h after reperfusion, and the radioactivity uptake was quantified by gamma-counting of infarcted and ischemic noninfarcted cardiac tissues. Alternatively, the radiotracer was injected at 2 h after reperfusion, and the uptake was measured at 1, 3, 6, and 24 h after injection. In vivo planar imaging was performed on a gamma-camera using a parallel-hole collimator. The distribution of radioactivity was qualitatively examined by autoradiography. The relationship between the uptake of the radiotracer in the area at risk and the ischemic duration was examined by gamma-counting. Temporally, the radioactivity uptake in the area at risk maximized when the radiotracer was injected before 3 h after reperfusion. Injections at 6 and 24 h after reperfusion resulted in a 30% and 50% reduction in uptake, respectively. However, when the injection was done early (2 h after reperfusion), the tracer was retained in the area at risk with little washout for at least 24 h. Spatially prominent hot-spot uptake was seen in all cases of planar imaging. In autoradiography, the distribution of radioactivity predominantly coregistered with the infarcted regions. This distribution profile was confirmed by direct gamma-counting. In addition, the absolute radiotracer uptake in the infarcted and ischemic noninfarcted tissues, in terms of percentage injected dose per gram, was independent of the ischemic duration. (99m)Tc-C2A-GST has an uptake profile in the area at risk that is appropriate for imaging cardiac cell death in the acute phase.

Abstract  To treat cutting oil wastewater produced in metal surface treatment industry, Ultrasonication (US)-Fenton process, which is one of the advanced oxidation processes, was used. The optimum conditions to treat non-biodegradable pollutants using the US-Fenton process were that the application rates of H2O2 and FeSO4 were 10% and 3 g/L, respectively, the value of pH was 3, and the ultrasonication time was 30 min. It identified non-degradable pollutants such as ethylene diamine tetraacetic acid (EDTA) and Triethanolamine (TEA) in the cutting oil wastewater. TLC analysis of two compounds of treated water by the coagulation process was similar to that of raw water. However, TLC analysis of two compounds of US-Fenton process was different from that of raw water, meaning that US-Fenton process decomposed the EDTA and TEA. To study the possibility of application with the US-Fenton process to pilot plant, the pollutants treatment efficiency of three different methods, such as US-Fenton process, activated sludge process and coagulation process, in continuous experiments were compared. The removal rate of pollutants by the US-Fenton process according to the effluent time was higher than any other processes. The removal rates of COD, SS, T-N and T-P by US-Fenton process were 98, 93, 75 and 95%, respectively.

Abstract  UNLABELLED: 99mTc-EC20 is a folate receptor (FR)-targeted imaging agent consisting of the vitamin folate conjugated to 99mTc. FR is expressed on a variety of epithelial cancers, with advanced cancers often expressing FR at significantly higher levels than earlier stages of the disease. The goals of this pilot study were to determine the percentages of various solid tumors that accumulate 99mTc-EC20 in vivo and to correlate 99mTc-EC20 uptake with immunohistochemistry (IHC) analysis of FR expression in available biopsied tumor tissue.

METHODS: A total of 154 patients with proven or suspected cancer and at least one lesion of > or =1.5 cm underwent imaging with 99mTc-EC20. The majority of these patients (77%) had a diagnosis of renal cell carcinoma. The remaining patients had a variety of other solid tumors. Whole-body planar images were obtained 1-2 h after injection, followed by SPECT of the region containing index lesions. The uptake of 99mTc-EC20 in tumors was scored as no uptake, mild uptake, or marked uptake. The resultant 99mTc-EC20 data were analyzed for correlation with the expression of the alpha-isoform of FR, as determined by IHC analysis, in tissue available from prior or subsequent surgery or biopsy.

RESULTS: The administration of 99mTc-EC20 was well tolerated. Tumors with increased 99mTc-EC20 uptake were identified in 68% of patients, and IHC results were positive for the expression of the alpha-isoform of FR in 67% of patients. The agreement between methods was 61% overall (kappa = 0.096; 95% confidence interval = -0.085 to 0.277), with 72% agreement of positive results and 38% agreement of negative results.

CONCLUSION: In vivo imaging with 99mTc-EC20 identified approximately two thirds of patients as having FR-positive tumors. Agreement between imaging and in vitro IHC was poor but was potentially confounded by a lack of correlation between the time of tissue sampling and the time of 99mTc-EC20 imaging, the heterogeneous expression of FR in metastatic lesions from the same patient, and the inability to detect the beta-isoform of FR by IHC. This pilot study of 99mTc-EC20 scintigraphy indicates that the agent is safe and well tolerated and that this noninvasive procedure may have utility in selecting patients likely to benefit from FR-targeted therapy.

Abstract  Apoptosis (programmed cell death) is a critical element in normal physiology and in many disease processes. Phosphatidylserine (PS), one component of cell membrane phospholipids, is normally confined to the inner leaflet of the plasma membrane. Early in the course of apoptosis, this phospholipid is rapidly exposed on the cell's outer surface. Annexin V, an endogenous human protein, has a high affinity for membrane-bound PS. This protein has been labeled with fluorescein and has been used to detect apoptosis in vitro. We describe the use of radiolabeled annexin V to detect apoptosis in vivo. The results are compared to histologic and flow cytometric methods to identify cells and tissues undergoing apoptosis. Annexin V was coupled to hydrazinonicotinamide (HYNIC) and radiolabeled with 99mTc. Bioreactivity of 99mTc-HYNIC annexin V was compared with fluorescein isothiocyanate (FITC)-labeled annexin V in cultures of Jurkat T-cell lymphoblasts and in ex vivo thymic cell suspensions undergoing apoptosis in response to different stimuli. In addition, the uptake of FITC annexin V and 99mTc-HYNIC annexin V was studied in heat-treated necrotic Jurkat T-cell cultures. In vivo localization of annexin V was studied in Balb/c mice injected with 99mTc-HYNIC annexin V before and after induction of Fas-mediated hepatocyte apoptosis with intravenously administered antiFas antibody. Membrane-bound radiolabeled annexin V activity linearly correlated to total fluorescence as observed by FITC annexin V flow cytometry in Jurkat T-cell cultures induced to undergo apoptosis in response to growth factor deprivation (N = 10, r2 = 0.987), antiFas antibody (N = 8, r2 = 0.836) and doxorubicin (N = 10, r2 = 0.804); and in ex vivo experiments on thymic cell suspensions with dexamethasone-induced apoptosis from Balb/c mice (N = 6, r2 = 0.989). Necrotic Jurkat T-cell cultures also demonstrated marked increases in radiopharmaceutical (4000-5000-fold) above control values. AntiFas antibody-treated Balb/c mice (N = 6) demonstrated a three-fold rise in hepatic uptake of annexin V (P < 0.0005) above control (N = 10), identified both by imaging and scintillation well counting. The increase in hepatic uptake in antiFas antibody-treated mice correlated to histologic evidence of fulminant hepatic apoptosis. These data suggest that 99mTc-HYNIC annexin V can be used to image apoptotic and necrotic cell death in vivo.

Abstract  Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17beta-oestradiol (E(2)) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER-) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using (99m)Tc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER- MDA MB231 breast cancer cell lines were exposed to 1 n M E(2) or a combination of 1 n M E(2) plus 100 n M tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of (99m)Tc-depreotide (0.5 n M-15 n M) in the absence and the presence of 20 micro M of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E(2)-induced changes in (99m)Tc-depreotide binding were identified by means of western blotting. Mean K(d) values for (99m)Tc-depreotide were 13 n M, 7 n M and 4 n M for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E(2), the ER+ cell line T47D demonstrated a mean increase of 81% ( P<0.05) in (99m)Tc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E(2) blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E(2) showed a mean decrease in (99m)Tc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B(max) values did not change in ZR75-1 cells exposed to E(2) in combination with an ER antagonist as compared to control cells. Finally, no influence of E(2) on (99m)Tc-depreotide binding was observed in the ER- cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E(2) and was restored to the original detection level after E(2) treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.

Abstract    Issue Title: Abstracts, Annual Congress of the EANM 2013, Lyon, France

Abstract  Iron metallodrugs comprise mineral supplements, anti-hypertensive agents and, more recently, magnetic nanomaterials, with both therapeutic and diagnostic roles. As biologically-active metal compounds, concern has been raised regarding the impact of these compounds when emitted to the environment and associated ecotoxicological effects for the fauna. In this work we assessed the relative stability of several iron compounds (supplements based on glucoheptonate, dextran or glycinate, as well as 3,5,5-trimethylhexanoyl (TMH) derivatives of ferrocene) against high affinity models of biological binding, calcein and aprotransferrin, via a fluorimetric method. Also, the redox-activity of each compound was determined in a physiologically relevant medium. Toxicity toward Artemia salina at different developmental stages was measured, as well as the amount of lipid peroxidation. Our results show that polymer-coated iron metallodrugs are stable, non-redox-active and non-toxic at the concentrations studied (up to 300 µM). However, TMH derivatives of ferrocene were less stable and more redox-active than the parent compound, and TMH-ferrocene displayed toxicity and lipid peroxidation to A. salina, unlike the other compounds. Our results indicate that iron metallodrugs based on polymer coating do not present direct toxicity at low levels of emission; however other iron species (eg. metallocenes), may be deleterious for aquatic organisms. We suggest that ecotoxicity depends more on metal speciation than on the total amount of metal present in the metallodrugs. Future studies with discarded metallodrugs should consider the chemical speciation of the metal present in the composition of the drug.

Abstract    Two hundred sixteen Angus crossbred steers (230 kg ± 5.6) purchased from sale barns were utilized to determine the impact of trace mineral source and concentration on performance, tissue metabolites, and lipid metabolism. Treatments during the 27-d receiving phase consisted of 1) inorganic trace mineral (125 mg CuSO^sub 4^/d per head, 360 mg ZnSO^sub 4^/d per head, 200 mg MnSO^sub 4^/d per head, and 12.5 mg CoCO^sub 3^/d per head) or 2) organic trace mineral (iso-amounts of Cu, Zn, Mn amino acid complexes, and Co glucoheptonate). On d 0 and 27, blood samples were collected from 3 steers per pen (pen = experimental unit). On d 28, steers were transitioned to a high concentrate finishing diet containing different concentrations of Co. Treatments during the finishing phase consisted of 1) control (no supplemental Co); 2) 0.10 mg Co/kg DM from cobalt glucoheptonate; and 3) 1.0 mg Co/kg DM from cobalt glucoheptonate. The same 3 steers per pen were bled on d 84 and 224 of the finishing phase. During the receiving phase, red blood cell superoxide dismutase activity was greater (P < 0.03) for organic- vs. inorganic-supplemented steers. During the finishing phase, overall ADG tended (P < 0.06) to be greater for steers receiving 1.0 mg Co/kg DM. Steers receiving 1.0 mg Co/kg DM had greater YG (P < 0.04) and back fat thickness (P < 0.04) than steers receiving 0.10 mg Co/kg DM. Serum, liver, and LM B12 concentrations increased (P < 0.04) as dietary Co concentration increased. [PUBLICATION ABSTRACT]

Abstract  The infection imaging properties of a high-affinity 99mTc-labeled chemotactic peptide receptor agonist (N-formyl-methionyl-leucyl-phenylalanine-lysine; N-For-MLFK) were compared with a low-affinity agonist (N-Acetyl-MLFK; N-Ac-MLFK), a moderate-affinity antagonist (N-isobutyloxycarbonyl-MLFK; N-IBoc-MLFK) and non-specific inflammation imaging agents. All peptides were prepared by solid-phase methods and purified by high-performance liquid chromatography. The products were assayed in vitro for N-formyl-methionyl-leucyl-phenylalanine receptor binding and superoxide production. Three types of studies were performed in rabbits with Escherichia coli infection: (Study A) Four groups of six animals were coinjected with 99mTc-N-For-MLFK-hydrazinonicotinamide (N-For-MLFK-HYNIC) plus 111In-immunoglobulin G, 111In-red blood cells or 111In-diethylene triamine pentaacetic acid. (Study B) Three groups of six rabbits were coinjected with 111In-leukocytes plus 99mTc-N-For-MLFK-HYNIC, 99mTc-N-Ac-MLFK-HYNIC or 99mTc-N-IBoc-MLFK-HYNIC. (Study C) Two groups of six rabbits were injected with 99mTc-N-For-MLFK-HYNIC and 111In-leukocytes with and without an excess of antagonist. In all three studies, the radiopharmaceuticals were injected 24 hr after infection and dual photon (99mTc and 111In) gamma camera images were acquired at 2-3 and 16-18 hr later. Target-to-background (T/B) ratios were calculated for regions of interest drawn over the infected and contralateral normal tissue. N-For-MLFK, N-Ac-MLFK and N-IBoc-MLFK had EC50s for receptor binding of 2.0, 830 and 150 nM, respectively. The corresponding EC50s for superoxide production were 20.0, approximately 10(3) and > 10(4). Study A demonstrated that the T/B for 99mTc-N-For-MLFK-HYNIC was higher than for any of the nonspecific imaging agents (p < 0.001), and 111In-immunoglobulin G had a higher T/B ratio than 111In-diethylenetriamine pentaacetic acid (p < 0.01) or 111In-red blood cells (p = NS). Study B showed that 99mTc-N-For-MLFK-HYNIC had a higher T/B ratio than the other peptides (p < 0.001). 111In-leukocytes and 99mTc-N-IBoc-MLFK-HYNIC had comparable T/B ratios, which were higher than for 99mTc-N-Ac-MLFK-HYNIC (p < 0.05). Study C demonstrated that coinjection with an antagonist resulted in a significant reduction in the T/B ratio for 99mTc-N-For-MLFK-HYNIC (p < 0.001), but did not affect the T/B ratio for 111In-leukocytes. Nonspecific mechanisms contribute minimally to the localization of 99mTc-chemotactic peptide analogs at sites of infection and the majority of the accumulation appears to be receptor mediated. Also, chemotactic peptide receptor antagonists can be used for infection imaging. These results provide important new insights for future radiopharmaceutical development.

Abstract  This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 ((186)Re)-labeled liposomal doxorubicin (Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck tumor xenografts and normal organs. Doxil and control polyethylene glycol (PEG)-liposomes were labeled using (186)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) method. Tumor-bearing rats received either no therapy (n=6), intravenous Doxil (n=4), or escalating radioactivity of (186)Re-Doxil (185-925 MBq/kg) or (186)Re-PEG-liposomes (1110-1665 MBq/kg) and were monitored for 28 days. Based on body weight loss and systemic toxicity, MTD for (186)Re-Doxil and (186)Re-PEG-liposomes were established at injected radioactivity/body weight of 740 and 1480 MBq/kg, respectively. (186)Re-injected radioactivity/body weight for therapy studies was determined to be 555 MBq/kg for (186)Re-Doxil and 1295 MBq/kg for (186)Re-PEG-liposomes. All groups recovered from their body weight loss, leucopenia, and thrombocytopenia by 28 days postinjection. Normalized radiation absorbed dose to tumor was significantly higher for (186)Re-Doxil (0.299±0.109 Gy/MBq) compared with (186)Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate therapy study, tumor volumes were significantly smaller for (186)Re-Doxil (555 MBq/kg) compared with (186)Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide therapy with (186)Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity.

Abstract  Issue Title: Abstracts, Annual Congress of the EANM 2011, Birmingham, UK

Abstract  Several abstracts including antibiotic use in animals and the impact of the growth promoter ban in Europe, enzymatic degradation of prions and prevention of transmissible spongiform encephalopathies, and mycotoxin detoxification and microorganisms in feeds, among others, are presented.

Abstract  The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.

Abstract  In the direct labeling of antibodies with Re-186, 188, the lower redox potential of ReO4- than TcO4- requires the addition of excess SnCl2 and a medium-chelating agent for stabilizing the excess of SnCl2 in solution. Through extensive tests, sodium glucoheptonate (GH) was chosen as an excellent stabilizer for SnCl2 and also the reduced Re(V) from a variety of chelators, such as citrate, cyclodextrin, tartrate, inositol, glucose, glycine, etc. ReO4- solution was then quantitatively reduced for 2 h with newly prepared SnCl2(GH) solution. Then, we directly incorporated the reduced Re to the antibodies IgG modified with 135 ford of NaHSO3 and 3500 fold of 2-ME, and more than 90% of specific binding was yielded in 100-150 min at room temperature. TLC analysis indicated that less than 5% of activity was in the colloid form. Radiolabeled antibodies IgG were stable to the challenging of 700 fold of DTPA, and also showed fine in vivo stability.

Abstract  The effects of estradiol dipropionate (EDP) or calcium glucoheptonate (Ca) on the morphology and stereology of the PRL cells in 14-month-old Wistar female rats were studied. The animals were treated daily with EDP in the dose of 0.625 mg/kg b.w. or calcium glucoheptonate (Ca; 11.4 mg/kg b.w) for two weeks. The controls were injected with vehicle alone by the same schedule. Mammotrophs (PRL cells) were immunocytochemically localized by the PAP method. Blood PRL concentration was determined by Delfia procedure. In animals treated with EDP the volume of both, PRL cells and their nuclei, as well as the volume densities were significantly (p<0.05) increased by 17%, 9% and 38%, respectively, in comparison with the controls. In animals treated with Ca all morphometric parameters were insignificantly (p > 0.05) decreased compared to control rats. Serum concentration of PRL was significantly increased (p<0.05) by 17% after estradiol treatment, but in Ca-treated females this parameter was insignificantly (p>0.05) changed by 2% compared to controls. Based on these results, it can be concluded that EDP expresses a strong stimulatory effect on the morphology and function of pituitary PRL cells.

Abstract  The effects of multiple doses of estradiol dipropionate (EDP) or calcium glucoheptonate (Ca) on the growth and function of pituitary somatotropes (GH cells) were studied. Female middle-aged rats were receiving i.p. EDP (0.625 mg i.p./kg b.w), or Ca (11.4 mg/kg b.w) every day for two weeks. Blood samples were collected for hormone analyses and pituitaries dissected for histological and morphometric evaluation 24 h after the last injection. GH-producing cells were examined using the peroxidase-antiperoxidase (PAP) immunohistochemical procedure. Both EDP- and Ca-treatment significantly decreased all morphometric parameters of GH cells (p < 0.05) in comparison with the corresponding controls. Serum concentration of growth hormone (GH) in EDP- or Ca-treated groups was lower by 65% and 13% (p < 0.05) respectively, comparing to the controls. The difference between all morphometric parameters of EDPL and Ca-treated rats was statistically significant (p<0.05) in relation to the controls. These findings suggest that multiple EDP, or Ca application affects (directly or indirectly) the control of growth and secretory activity of GH cells in middle-aged female rats.