Impact of 18F-fluoride PET-CT on implementing early treatment of painful bone metastases with Sm-153 EDTMP

This study evaluated the diagnostic impact of using skeletal ¹⁸F-fluoride PET/CT on patients with painful bone metastases to schedule an early palliative radionuclide treatment. Methods: The skeletal involvement from prostate cancer metastases was assessed by both ^99mTc-diphosphonate bone scan (BS) and ¹⁸F-fluoride PET/CT within four weeks in 24 patients (67.7 ± 5.1 years) suffering from a borderline degree of bone pain for which radionuclide palliation was not shortly planned for administration. The BS and ¹⁸F-fluoride PET/CT results were compared, assessing the number and extension of the skeletal sites involved. Afterward, the patients were randomly assigned either to the study group (N = 12) receiving radionuclide therapy (Samarium-153 EDTMP) or to the control group (N = 12) not receiving radionuclide therapy. The short-term results from the radionuclide palliation group (evaluated with a visual analogue scale) were compared with the controls. Results: Overall, at BS, 7.6 ± 1.4 sites were considered metastatic, involving at least 5 ± 1 body regions. At ¹⁸F-fluoride PET/CT, 116 ± 19 sites presented metastatic involvement with 12/12 body regions concerned. No differences were found in regards to either the number of metastatic sites or regions at both BS and ¹⁸F-fluoride PET/CT between the study group and controls (p = ns). At CT, 88 blastic metastases were identified, whereas 110 were mainly lytic. Most of mainly lytic lesions were not detectable at BS. The reduction in total discomfort and bone pain in the study group was significantly greater than in the controls (p < 0.0001). Conclusion: Sm-153 EDTMP therapy should be considered for patients with early bone pain from prostate cancer even if their BS only indicates a few metastases before the initiation of a severe pain syndrome. ¹⁸F-fluoride PET/CT may be helpful in deciding if the implementation of bone pain palliation using bone-seeking radionuclides at pain onset is necessary.     

Laboratory experiments to characterize radiochloride diffusion in unsaturated soils

Diffusion transport of ³⁶Cl was examined in seven soils under unsaturated conditions in tubes packed with two portions of each soil having different ³⁶Cl activity concentrations. Apparent diffusion coefficients (D_a) derived from diffusion profiles varied within a narrow range (from 3×10^?10 to 7×10^?10 m² s^?1) confirming the minor effect of soil properties on the diffusion of a non-reactive radionuclide like ³⁶Cl. Instead, packing conditions had a major effect. Solid–liquid distribution coefficients (K_d) derived from D_a (0.02–0.2 L kg^?1) were systematically lower than those obtained from batch experiments (0.6–1.0 L kg^?1), but with a similar variation pattern among soils. The low values of K_d (Cl) confirmed an almost negligible radiochloride–soil interaction.     

New CT criteria for nodal staging in non-small cell lung cancer

ObjectiveThe purpose of our study was to develop a simple noninvasive technique for nodal staging using routine preoperative computed tomography (CT).Materials and methodsThe institutional review board approved this retrospective study, and written informed consent to perform the initial and follow-up CT studies was obtained from all patients. Preoperative CT findings (n= 218 patients with resectable non-small cell lung cancer) and pathological diagnoses after surgical resection were evaluated. Using CT images, lymph node section area, circumference, and lesion attenuation values (LAVs) were drawn freehand, and the short axis (SA) and long axis (LA) were measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze the section area, circumference, and LAVs.ResultsBased on ROC curves, two cut-off values, lymph node section area > 30 mm² and circumference > 25 mm, showed greater sensitivity for nodal staging than the conventional criterion of lymph node SA ≥ 10 mm or the LA, SA/LA ratio or LAVs. Using lymph node section area > 30 mm² for diagnosis, the sensitivity, specificity, and accuracy of nodal staging were 90.5%, 56.3%, and 58.3%, respectively. Using lymph node circumference > 25 mm, the values were 76.2%, 70.4%, and 70.8%, respectively.ConclusionLymph node section area > 30 mm² and circumference > 25 mm can serve as supportive criteria used by radiologists and surgeons to determine nodal staging. If these CT criteria are met, use of a more sensitive procedure such as positron emission tomography or mediastinoscopy is recommended.Concise abstractCT is used routinely during preoperative management of lung cancer. Based on ROC analyses, the cut-off values for surface area, circumference, the SA/LA ratio, and LAVs for diagnosis of lymph node metastasis were 30 mm², 25 mm, 0.65, and 50 Hounsfield units, respectively. Our findings indicate that lymph node surface area > 30 mm² and circumference > 25 mm are supportive criteria that can be used by radiologists and thoracic surgeons to determine nodal staging and surgical indications.     

Improving prostate brachytherapy quality assurance with MRI–CT fusion–based sector analysis in a phase II prospective trial of men with intermediate-risk prostate cancer

PurposeWe combined sector analysis with MRI–CT fusion to comprehensively assess postimplant dosimetry after prostate brachytherapy.Methods and MaterialsSubjects were 50 men with intermediate-risk prostate cancer treated with ¹²⁵I brachytherapy in a prospective phase II clinical trial. On Day 30 after the implantation, dosimetry was evaluated in the prostate base, midgland, and apex regions on fused MRI–CT scans and CT scans. Volumes of each sector receiving 100% of the prescribed dose (V₁₀₀) and doses to 90% of each sector (D₉₀) were also calculated on the ultrasonogram used for treatment planning and compared with values derived from CT and fused MRI–CT scans.ResultsFused MRI–CT scans revealed lower-than-expected doses for the whole prostate (V₁₀₀ = 91.3%, D₉₀ = 152.9 Gy) compared with CT scans (98.5% and 183.6 Gy, p < 0.0001) and lower doses to the prostate base (V₁₀₀ = 79%, D₉₀ = 130 Gy) vs. CT (96% and 170 Gy, p < 0.0001). However, lower doses to the prostate base did not adversely affect biochemical outcomes in men with biopsy-proven disease at the base. At a median followup time of 42 months, the mean prostate-specific antigen level for all patients was 0.3 ng/mL, and no patient had experienced biochemical or clinical progression or recurrence.ConclusionsMRI–CT fusion–based sector analysis was feasible and revealed significantly lower doses to the prostate base than doses estimated from CT alone, although this did not affect biochemical outcomes. MRI–CT fusion–based sector analysis may be useful for developing MRI-based dosimetric markers to predict disease outcomes and treatment-related morbidity.     

Whole-body 18F-FDG PET/CT for M staging in the patient with newly diagnosed nasopharyngeal carcinoma: Who needs?

ObjectiveAlthough whole-body fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) (¹⁸F-FDG PET/CT) is commonly used for M staging of newly diagnosed nasopharyngeal carcinoma (NPC), some patients may not benefit from this procedure. The present study investigated which patients require this modality for M staging.MethodsWhole-body ¹⁸F FDG PET/CT results and clinical data were collected for 264 patients with newly diagnosed NPC. The relationships between distant metastasis and age, gender, pathological type, lesion size, SUVmax-T, T staging, N staging, SUVmax-N and Epstein-Barr virus (EBV) quantity were retrospectively analysed to identify factors associated with increased risk.ResultsOf the 264 patients, only 37 (14.0%) were diagnosed with distant metastasis. Using multiple logistic regression analysis, EBV-positivity (OR = 13.1; 95% CI:1.61,106.80), N staging (OR = 3.05; 95% CI:1.41,6.63) and T staging (OR = 2.16; 95% CI:1.10, 4.24) were significantly related to distant metastasis (all P < 0.05). EBV DNA levels ≥ 9000 copies/ml, N3 stage and T4 stage were identified as high risk factors. A low risk of distant metastasis was found in patients with 0–1 risk factors and in those with 2 specific risk factors, T3/T4 and N2/N3 staging. Patients with EBV DNA levels ≥9000 copies/ml and N3 or T4 staging and those with 3 risk factors had a medium or high risk, with a much higher incidence of distant metastasis (χ² = 29.896, P = 0.000), and needed a whole-body ¹⁸F FDG PET/CT for M staging.ConclusionsDue to the low incidence of distant metastasis, only patients with medium or high risk need to undergo a whole-body scan.     

Haemodynamic responses of wearing low-pressure sports compression tights during an orthostatic challenge in healthy individuals

Objectives

While previous studies have demonstrated an ergogenic effect of sport compression garments in exercise performance and recovery, the possible underlying mechanisms remain unclear. Claims for improved venous return from wearing sport compression garments with a low compression pressure remain unproven. The aim of this study was to determine the pressure profile exerted by low-pressure sports compression tights, and to investigate using a non-invasive Doppler ultrasound cardiac output monitor (USCOM), whether the compression applied will influence haemodynamic responses during an orthostatic challenge.

Comparison between perfusion computed tomography and dynamic contrast-enhanced magnetic resonance imaging in assessing glioblastoma microvasculature

PurposePerfusion computed tomography (PCT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide independent measurements of biomarkers related to tumor perfusion. The aim of this study was to compare the two techniques in assessing glioblastoma microvasculature.Materials and methodsTwenty-five patients diagnosed with glioblastoma (14 males and 11 females; 51 ± 11 years old, ranging from 33 to 70 years) were includede in this prospective study. All patients underwent both PCT and DCE-MRI. Imaging was performed on a 256-slice CT scanner and a 3-T MRI system. PCT yielded permeability surface-area product (PS) using deconvolution physiological models; meanwhile, DCE-MRI determined volume transfer constant (K^trans) using the Tofts-Kermode compartment model. All cases were submitted to surgical intervention, and CD105-microvascular density (CD105-MVD) was measured in each glioblastoma specimen. Then, Spearman’s correlation coefficients and Bland-Altman plots were obtained for PS, K^trans and CD105-MVD. P < 0.05 was considered statistically significant.ResultsTumor PS and K^trans values were correlated with CD105-MVD (r = 0.644, P < 0.001; r = 0.683, P < 0.001). In addition, PS was correlated with K^trans in glioblastoma (r = 0.931, P < 0.001). Finally, Bland-Altman plots showed no significant differences between PS and K^trans (P = 0.063).ConclusionPCT and DCE-MRI measurements of glioblastoma perfusion biomarkers have similar results, suggesting that both techniques may have comparable utility. Therefore, PCT may serve as an alternative modality to DCE-MRI for the in vivo evaluation of glioblastoma microvasculature.     

Analysis of 49 autosomal SNPs in three ethnic groups from Iran: Persians,Lurs and Kurds

A total number of 149 individuals from Iran (Persians, Lurs and Kurds) were analyzed for 49 autosomal SNPs using PCR, SBE and capillary electrophoresis. No deviation from Hardy–Weinberg expectations was observed. One SNP pair (rs1015250–rs251934) showed significant linkage disequilibrium in Kurds. However, this was most likely due to chance. High intrapopulation variability and no significant population structure were observed among the three ethnic groups from Iran. Pairwise F_ST values obtained from the mean numbers of pairwise differences between SNP profiles were calculated for Persians, Lurs, Kurds and eighteen other worldwide populations. For each of the three Iranian ethnic groups, the lowest F_ST values calculated between an Iranian and non-Iranian populations were observed between Iranians and populations in Iraq and Turkey. The three Iranian ethnic groups grouped together with other West Asian populations in the MDS plot drawn from the F_ST values. Statistical parameters of forensic interest calculated for the Iranian ethnic groups showed values of the same order of magnitudes as those obtained for Asians. The mean match probability calculated for the 49 SNPs ranged from 1.7 x 10⁻¹⁸ for Kurds to 1.3 x 10⁻¹⁹ for Persians. Despite the low level of genetic structure observed among Persians, Lurs and Kurds, a single autosomal SNP database should be used with care when extending its forensic application to other Iranian ethnic groups.     

A comparison of preplan transrectal ultrasound with preplan-CT in assessing volume and number of seeds needed for real-time ultrasound-based intra-operative planning in prostate 125I seed implantation

PurposeIntra-operative (real-time) treatment planning has been adapted by many institutions for low–dose rate prostate brachytherapy. Although this allows dosimetric planning to be done during the procedure, preplan imaging to obtain a prostate volume is essential to identify the number of seeds to ensure adequate volume coverage. Currently, there is no consensus regarding the most appropriate imaging to obtain this information. We conducted a retrospective study to compare how volumes obtained from preplan CT (p-CT) scans or preplan transrectal ultrasound (p-TRUS) correlated with real-time ultrasound and postimplant CT volumes and the difference in accuracy of seed estimation between these techniques.Methods and MaterialsNinety-two patients underwent ¹²⁵I permanent seed implants at Thomas Jefferson University Hospital between February 2002 and August 2008. Fifty-one patients underwent p-TRUS before intra-operative planning and 41 patients were evaluated by p-CT.ResultsThe median difference in volume between preimplant imaging and the intra-operative planning ultrasound was 3.59 and 5.2 cc for patients who underwent p-TRUS and p-CT, respectively. p-TRUS volumes more closely correlated with real-time intra-operative volumes (R = 0.84 in all patients and R = 0.91 in hormone-naïve patients) vs. p-CT (R = 0.82). The median number of seeds wasted using p-CT was 18 vs. 7 using volumes derived from p-TRUS.ConclusionsThe number of seeds ordered could be more accurately obtained from p-TRUS volumes, and this translated into less seed wastage. Our findings indicate that p-TRUS is a more accurate and an economically superior alternative to p-CT imaging in the era of real-time ultrasound planning.     

Differentiation and diagnosis of benign and malignant testicular lesions using 18F-FDG PET/CT

ObjectivesThe purpose of this study was to evaluate the differential diagnostic value of ¹⁸F-fluorodeoxy glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for benign and malignant testicular lesions.MethodsThe PET/CT scans of 53 patients with testicular lesions confirmed by biopsy or surgical pathology were retrospectively analyzed. There were 32 cases of malignant tumors and 21 cases of benign lesions. Differences in the maximum standardized uptake value (SUVmax) measurements and the SUVmax lesion/background ratios between benign and malignant lesions were analyzed. The diagnostic value of this PET/CT modality for the differential diagnosis of benign versus malignant testicular lesions was calculated.ResultsThe differences in the SUVmax measurements and the SUVmax lesion/background ratios between benign and malignant lesions were statistically significant (SUVmax: Z = −4.295, p = 0.000; SUVmax lesion/background ratio: Z = −5.219, p = 0.000); specifically, both of these indicators were higher in malignant lesions compared to benign lesions. An SUVmax of 3.75 was the optimal cutoff value to differentiate between benign and malignant testicular lesions. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this PET/CT modality in the differential diagnosis of benign versus malignant testicular lesions were 90.6%, 80.9%, 86.8%, 87.9%, and 85.0%, respectively.Conclusions¹⁸F-FDG PET/CT can accurately identify benign and malignant testicular lesions.     

A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin

Background and purposeThe diagnosis of patients with fever of unknown origin (FUO) remains a challenging medical problem for internal medicine. A reliable estimate of the diagnostic performance of FDG-PET and FDG-PET/CT in the assessment of FUO unidentified by conventional workup has never been systematically assessed, and present systematic review was aimed at this issue.MethodsA systematic search for relevant studies was performed of the PubMed, Embase, and Cochrane databases. Methodological quality of each study was assessed. Sensitivity, specificity and area under the curve (AUC) were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous.ResultsThe inclusion criteria were met by nine studies. Overall, the studies had good methodological quality. Pooled sensitivity and specificity of FDG-PET for the detection of FUO were 0.826 (95% CI; 0.729–0.899) and 0.578 (95% CI; 0.488–0.665), respectively, and the AUC was 0.810. Heterogeneity among the results of FDG PET studies was present (QSE = 12.40, I² = 67.7%; QSp = 35.98, I² = 88.9%). Pooled sensitivity and specificity of FDG-PET/CT were 0.982 (95% CI; 0.936–0.998) and 0.859 (95% CI; 0.750–0.934), respectively, and the AUC was 0.947. We did not find any statistical differences in the AUC and Q* index between FDG-PET and FDG-PET/CT (Z = 0.566, p > 0.05).ConclusionsAlthough the FDG-PET studies that we examined were heterogeneous, FDG-PET appears to be a sensitive and promising diagnostic tool for the detection of the causes of FUO. FDG-PET/CT should be considered among the first diagnostic tools for patients with FUO in whom conventional diagnostics have been unsuccessful.     

Differentiation of small intrahepatic mass-forming cholangiocarcinoma from small liver abscess by dual source dual-energy CT quantitative parameters

PurposeTo investigate the use of dual source dual-energy CT (DECT) quantitative parameters compared with the use of conventional CT for differentiating small (≤3 cm) intrahepatic mass-forming cholangiocarcinoma (IMCC) from small liver abscess (LA) during the portal venous phase (PVP).Material and methodsIn this institutional review board-approved, retrospective study, 64 patients with IMCCs and 52 patients with LAs who were imaged in PVP using dual-energy mode were included retrospectively. A radiologist drew circular regions of interest in the lesion on the virtual monochromatic images (VMI), color-coded iodine overlay images, and linear blending images with a linear blending ratio of 0.3 to obtain CT value, its standard deviation, slope (k) of spectral curve and normalized iodine concentration (NIC). Two radiologists assessed lesion type on the basis of qualitative CT imaging features.ResultsCT values on VMI at 50–130 keV (20 keV-interval), k, and NIC values were significantly higher in IMCCs than in LAs (p < 0.0001). The best single parameter for differentiating IMCC from LA was CT value at 90 keV, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 89.1%, 86.5%, 87.9%, 89.1%, and 86.5%, respectively. The best combination of parameters was CT value at 90 keV, k, and NIC, with values of 87.5%, 84.6%, 83.6%, 87.5%, and 84.6%, respectively. Compared with CT value at linear blending images, CT value at 90 keV showed greater sensitivity (89.1% vs 60.9%, p < 0.0001) and similar specificity (86.5% vs 84.6%, p = 1.0000), and combined CT value at 90 keV, k, and NIC showed greater sensitivity (87.5% vs 60.9%, p < 0.0001) and similar specificity (84.6% vs 84.6%, p = 1.0000). Compared with qualitative analysis, CT value at 90 keV showed greater sensitivity (89.1% vs 65.6%, p = 0.0059) and specificity (86.5% vs 69.2%, p = 0.0352), and combined CT value at 90 keV, k, and NIC showed greater sensitivity (87.5% vs 65.6%, p = 0.0094) and similar specificity (84.6% vs 69.2%, p > 0.05).ConclusionQuantitative analysis of dual source dual-energy CT quantitative parameters showed greater accuracy than quantitative and qualitative analyses of conventional CT for differentiating small IMCCs from small LAs on single PVP scan.     

The effect of palatability of oral contrast media on compliance with drinking protocols,and on bowel opacification,in abdominal CT

PurposeTo assess whether palatability of oral contrast in CT has an impact on adherence to oral contrast media drinking protocols; and whether such variation has an impact on bowel opacification. Three different types of contrast media were compared; ionic and non-ionic iodinated oral contrast (Gastrografin^®, Diatrizoate, Schering AG), Gastromiro^® (Iopamidol, Bracco SpA) and the barium based contrast E-Z-Cat^® (E-Z-EM).Materials and methodsIn the first stage of the study 101 prospective patients were randomly given 1 L of a ～2% solution of Gastrografin^® or Gastromiro^® prior to a body CT scan. Data was recorded concerning the palatability of the oral contrast, drinking protocol compliance and bowel opacification. The second stage involved 66 prospective patients given Gastromiro^® or E-Z-Cat^® (again 1 L of ～2% solution).ResultsGastromiro^® had better palatability than Gastrografin^® (p = 0.001) and improved protocol compliance. E-Z-Cat had similar palatability to Gastromiro^®. Patients who found the oral contrast more palatable had improved drinking protocol compliance (p = 0.007) and improved small bowel opacification (p = 0.03). E-Z-Cat^® had similar palatability and protocol compliance to Gastromiro^® but better overall small bowel opacification (p = 0.001).ConclusionIn conclusion we suggest that the palatability of oral contrast is not only important to the patients overall experience of body CT, but that it is also linked to adherence with oral contrast drinking protocols leading to better bowel opacification.     

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

ObjectivePharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [¹⁸ F]fluoro-2-deoxyglucose ([¹⁸ F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice.MethodsA β₃-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [¹⁸ F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images.ResultsActivated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [¹⁸ F]FDG PET images. CL 316243 increased the total [¹⁸ F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [¹⁸ F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [¹⁸ F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R² = 0.55, p < 0.001) and between CT HU levels of IBAT and liver (R² = 0.69, p < 0.006) was observed.ConclusionsThe three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [¹⁸ F]FDG PET/CT.     

Design and biological evaluation of 99mTc-N2S2-Tat(49–57)-c(RGDyK): A hybrid radiopharmaceutical for tumors expressing α(v)β(3) integrins

The α(ν)β(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The aim of this research was to synthesize and assess the in vitro and in vivo uptake of ^99mTc-N₂S₂-Tat(49–57)-c(RGDyK) (^99mTc-Tat-RGD) in α(ν)β(3) integrin positive cancer cells and compare it to that of a conventional ^99mTc-RGD peptide (^99mTc-EDDA/HYNIC-E-[c(RGDfK)]₂). Methods: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys¹² side chain of the Tat(49–57)-spacer-N₂S₂ peptide. ^99mTc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for α(v)β(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT. Results: ^99mTc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for ^99mTc-Tat-RGD and 5.6% for ^99mTc-RGD. The IC₅₀ values were 6.7 nM (^99mTc-Tat-RGD) and 4.6 nM (^99mTc-RGD). Internalization in C6 cells was higher in ^99mTc-Tat-RGD (37.5%) than in ^99mTc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for ^99mTc-Tat-RGD (6.98% ± 1.34% ID/g at 3 h) than that of ^99mTc-RGD (3.72% ± 0.52% ID/g at 3 h) with specific recognition for α(v)β(3) integrins. Conclusions: Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for α(v)β(3) integrins, the hybrid ^99mTc-N₂S₂-Tat(49–57)-c(RGDyK) radiopharmaceutical is potentially useful for the imaging and possible therapy of tumors expressing α(v)β(3) integrins.     

Implications of CT imaging for postplan quality assessment in prostate brachytherapy

PurposePostplan quality assurance using CT shows considerable interobserver contour variability. We examined CT postplans of four experienced brachytherapists for comparison with MR-determined prostate volumes.Methods and MaterialsSeventy-five patients had CT and MR scans 1 month post-¹²⁵I prostate brachytherapy. CT scans were contoured by the treating physician and dosimetry calculated. The prostate was contoured independently on MR by one observer with extensive MR experience, the scans were fused and dosimetric parameters compared.ResultsThe mean prostate volume on CT was 38.3 cc (17.5–78.6 cc), on MR 33.3 cc (16.3–66.1 cc). On average, the volume on CT was 16.1% larger than on MR (range, 8% smaller to 64% larger). Craniocaudal discordance of the CT vs. MR prostate contours ranged from 4 mm cranial to 10 mm caudal to MR base and from 6 mm cranial to 14 mm caudal to MR apex. The CT prostate volume not only included an average of 90% of the MR prostate (range, 75–99%) but also included normal tissue (mean, 8.3 cc; range, 2.9–17.1 cc). The average difference between the calculated D₉₀ from CT contours vs. MR contours was 10.0 Gy (standard deviation, 8.8; range, ?37.6 to +41.6 Gy).ConclusionsOn average, only 90% of the MR-defined prostate is included in CT contours, while a volume of normal tissue is erroneously designated as prostate. Lack of awareness of this deficiency in planning and/or operative technique gives a false sense of appreciation of the true conformality, delays implementation of corrective measures, and risks unnecessary side effects.     

Therapeutic gene expression in transduced mesenchymal stem cells can be monitored using a reporter gene

AimWe constructed a recombinant adenovirus construct Ad5-sr39tk-IRES-VEGF₁₆₅ (Ad5-SIV) that contained a mutant herpes viral thymidine kinase reporter gene (HSV1-sr39tk) and the human vascular endothelial growth factor 165 (VEGF₁₆₅) gene for noninvasive imaging of gene expression. The recombinant adenovirus Ad5-SIV was transfected into rat bone marrow-derived mesenchymal stem cells (MSCs), and we measured the expression of HSV1-sr39tk and VEGF₁₆₅ to evaluate the feasibility of monitoring VEGF₁₆₅ expression using reporter gene expression.MethodsThe MSCs were infected with Ad5-SIV at various levels of infection (MOI), ranging from 0 to 100 infectious units per cell (IU/cell). The mRNA and protein expression levels of the reporter and therapeutic genes were determined using real-time RT-PCR, Western blot, ELISA and immunofluorescence. The HSV1-sr39tk expression in the MSCs was also detected in vitro using a cellular uptake study of the reporter probe ¹³¹I-FIAU. Gene expression was also evaluated in vivo by micro-Positron Emission Tomography/Computed Tomography (micro-PET/CT) imaging 1 day after injecting Ad5-SIV-tranfected MSCs into the left foreleg of the rat. The right foreleg was injected with non-transfected MSCs and served as an internal control.ResultsThe real-time RT-PCR results demonstrated a good correlation between the expression levels of HSV1-sr39tk mRNA and VEGF₁₆₅ mRNA (R² = 0.93, P < 0.05). The cellular uptake of ¹³¹I-FIAU increased with increasing viral titers (R² = 0.89; P < 0.05), and in the group that received an MOI of 100, a peak value of 30.15% ± 1.11% was found at 3 hours of incubation. The uptake rates increased rapidly between 30 and 150 minutes and reached a plateau after 150 minutes. The uptake rates of ¹³¹I-FIAU by the Ad5-SIV-infected cells were significantly higher than by the Ad5-EGFP-infected cells for all time points (t = 18.43-54.83, P < 0.05). Moreover, the rate of VEGF₁₆₅ protein secretion was highly correlated with the uptake rate of ¹³¹I-FIAU (R² = 0.84, P < 0.05). The radioactivity on the micro-PET/CT images was significantly higher in the left foreleg (which received the transfected MSCs) compared with the control foreleg.ConclusionsThese results suggest that radionuclide reporter gene imaging may be used to monitor gene expression in vivo.     

Comparison of intraoperative ultrasound with postimplant computed tomography--dosimetric values at Day 1 and Day 30 after prostate brachytherapy

PurposeTo compare the results of intraoperative dosimetry with those of postimplant computed tomography (CT)-based dosimetry after ¹²⁵I prostate brachytherapy.Methods and materialsWe treated 412 prostate cancer patients with ¹²⁵I prostate brachytherapy, with or without external beam radiotherapy at our institution. Neoadjuvant hormone therapy was administered to 331 patients (80.3%). Implantation was performed using an intraoperative interactive technique. Postimplant dosimetry was performed on Day 1 and Day 30 using CT imaging. The dosimetric results for the prostate, urethra, and rectum were compared among intraoperative ultrasound, and CT scans of Day 1 and Day 30.ResultsThe mean intraoperative minimal dose received by 90% of the prostate volume (D₉₀) was 118.8% of the prescribed dose vs. 106.4% for Day 1 (p < 0.01) and 119.2% for Day 30 (p = 0.25). There were no significant correlations between the intraoperative D₉₀ and the postimplant D₉₀ values (intraclass correlation coefficients = 0.42 and 0.33 for Day 1 and Day 30, respectively). Prostatic edema at Day 1 had the largest effect on the Day 1 D₉₀ (p < 0.01). The factor significantly affecting the Day 30 D₉₀ was neoadjuvant hormone therapy (p < 0.01). The mean Day 30 D₉₀ for the hormone-treated patients was 117.9%, compared with 124.6% for those who remained hormone naïve. The intraoperative and postimplant dosimetric values differed significantly for the urethra and rectum.ConclusionsOur results demonstrate that there are no significant differences between the D₉₀ assessments obtained intraoperatively and at Day 30 postoperatively. Furthermore, there are no definite correlations between intra- and postimplantation dosimetric values. Other D₉₀ values differed significantly between the intraoperative and postimplant dosimetry. This study suggests that dosimetry has negligible clinical utility for informing patients, at discharge, of whether or not their implants are adequate.     

137Cs tracing dynamics of soil erosion,organic carbon and nitrogen in sloping farmland converted from original grassland in Tibetan plateau

There is a shortage of research concerning the relationships between land-use change, soil erosion, and soil organic carbon (SOC) and nitrogen (N) dynamics in alpine environments such as those found in the Tibetan plateau. In this paper, typical sloping farmlands converted from grassland 50 years ago in eastern Tibet were selected to determine dynamics of soil erosion, SOC, and total N associated with land-use change. Soil samples were collected from sloping farmland and control fields (grassland). The ¹³⁷Cs, SOC, total N contents, and soil particle size fractions were analyzed in these samples. As compared with the control fields, ¹³⁷Cs, SOC, and total N inventories in the sloping farmlands decreased by 30%, 27%, and 33%, respectively. Meanwhile variations in the three parameters were enhanced in the sloping farmlands, with coefficients of variation (CVs) of 38%, 23%, and 20%, respectively, for ³⁷Cs, SOC, and total N. In addition, SOC and total N inventories significantly decreased with increasing soil erosion in the sloping farmland. In a sloping farmland with a steep 24° gradient, the ¹³⁷Cs inventory gradually increased along a downslope transect with its lowest value at 0 Bq m^?2 in the top-slope position (0 m). The soil clay (<0.002 mm) content in such an area increased with decreasing elevation (r=?0.95, p=0.001). Significant correlations between ¹³⁷Cs and clay (r=0.92, p=0.003), SOC (r=0.96, p=0.001), or total N (r=0.95, p=0.001) were also found in the farmland. These results showed that converting alpine grassland to sloping farmland accelerates soil erosion, losses in SOC and N, and increases the soil’s spatial variability. The combined impacts of tillage and water erosion contributed a significant decrease in the soil’s organic carbon and N storages. Particularly in steep sloping farmlands, tillage erosion contributed for severe soil loss, but the soil redistribution pattern was dominated by water erosion, not tillage erosion, due to the lack of boundaries across the field patches. It was also found that ¹³⁷Cs, SOC, and total N moved along the same pathway within these sloping farmlands, resulting in net C and N losses during soil redistribution. The negative influences of land-use conversion from grassland to farmland in sloping areas in the Tibetan plateau should be addressed.