A Formula to Calculate the Threshold for Radiotherapy Targets on PET Images: Simulation Study.

BACKGROUND: Positron emission tomography (PET) images are being applied for defining radiotherapy targets. However, a recognized method for defining radiotherapy targets is lacking. We investigate the threshold to outline the radiotherapy target of a tumor on PET images and its influencing factors, and then expressed it by formula. METHODS: PET imaging for spherical tumors with a different tumor diameter (D), under different system resolutions [full width at half maximum (FWHM)], in different backgrounds with different pixel sizes, was simulated. PET images were analyzed to determine the relationship between the threshold and the factors mentioned above. Finally, the simulation results were verified by phantom experiments. RESULTS: The threshold decreased sharply with D for D < 2 FWHM, reached the minimum of 31% at D = 2 FWHM and then increased slowly, and it tended to constant for D > 8 FWHM. The threshold decreased with FWHM for FWHM < D/2, reached a minimum at FWHM = D/2, and then increased. The threshold increased with pixel size for D ≤ FWHM and decreased for D > FWHM. The threshold was independent of the background. The relationship between the threshold and its influencing factors was expressed as a formula. The results of the phantom verification indicated that the error of the target volume delineation that was calculated by the formula was less than 9%. CONCLUSIONS: The threshold changes with tumor size, resolution of the PET system and pixel size according to certain rules. The formula to calculate the threshold could provide a method to estimate threshold to outline the radiotherapy target (tumor).

The value of 99mTc-labeled galactosyl human serum albumin single-photon emission computerized tomography/computed tomography on regional liver function assessment and posthepatectomy failure prediction in patients with hilar cholangiocarcinoma.

BACKGROUND: The aim was to evaluate the value of Tc-labeled galactosyl human serum albumin (Tc-GSA) with single-photon emission computerized tomography (SPECT) in the preoperative assessment of regional liver function and prediction of posthepatectomy liver failure (PHLF) in patients with hilar cholangiocarcinoma (hCCA). METHODS: Patients with hCCA who underwent Tc-GSA SPECT/computed tomography (CT) before hepatectomy were included. The liver functional parameters of functional liver density (FLD) and predictive residual index (PRI) were calculated based on Tc-GSA SPECT/CT. PHLF was defined according to the International Study Group of Liver Surgery criteria. Univariate and multivariate analyses were used to analyze the risk factors for PHLF. The prediction of PHLF was calculated using receiver operating characteristic curve. RESULTS: A total of 34 patients were included, 23 of whom underwent preoperative biliary drainage. FLD was significantly higher in patients with drained lobes than that in patients with undrained lobes (0.615 ± 0.190 versus 0.500 ± 0.211, P < 0.05). Sixteen patients suffered PHLF. The ratio of future remnant to total morphological liver volume, future remnant FLD, and PRI differed significantly in patients with and without PHLF according to univariate analysis. PRI was identified as the only independent factor for prediction of PHLF according to multivariate analysis. With a PRI of 0.78, it was possible to predict PHLF with a sensitivity of 83% and a specificity of 93%. CONCLUSIONS: Tc-GSA SPECT/CT can accurately assess regional liver function and is better able to predict PHLF than conventional methods in patients with hCCA.

Glomerular filtration rate measured by 99mTc-DTPA Gates method is not significantly affected by the premature or delayed initiation of image acquisition.

BACKGROUND: This study was performed to examine the effect of non-synchronization of the radiotracer injection and image acquisition on estimates of the glomerular filtration rate (GFR) by the Gates' method. METHODS: A total of 218 volunteers were selected as the research subjects. Two-sample method (GFRdt) and 99mTc-DTPA dynamic renal imaging (GFRGates) were used for determination of the GFR. We took GFRdt as the reference method, and then took the peak time of blood perfusion phase as the new time origin to ensure that all patients were unified on the time-radioactivity count rate curve. We moved the radioactivity curve on 9 time points to simulate premature (+20/+15/+10/+5 seconds), synchronous (0 seconds), and delayed (-20/-15/-10/-5 seconds) image acquisition in relation to the completion of tracer injection; we then acquired 9 GFRGates. The correlation and consistency of GFRGates and GFRdt were analyzed. Variance analysis compared the differences between different GFRGates. RESULTS: All 9 GFRGates had good correlation with GFRdt. GFRdt and GFRGates derived from -5, -10 and -15 s had the best correlation (r=0.827, P<0.01). The consistency between GFRGates derived from +20 s and GFRdt was the worst, and GFRGates derived from -15 s and GFRdt was the best. There were no significant differences between the 9 GFRGates. CONCLUSIONS: Non-synchronization of the radiotracer injection and image acquisition has no significant effect on the estimates of the GFRGates if the premature or delayed time between image acquisition and tracer injection is not more than 20 seconds.

Establish new formulas for the calculation of renal and isthmus depth in horseshoe kidney.

This study was performed to develop a new formula to estimate the renal and isthmus depth in horseshoe kidney, and to compare the new formula with previously published formulas.Renal depth, isthmus depth, vertebral thickness, and total thickness (T, cm) of the body at the level of the kidneys were measured by CT in 124 adults. Their sex, age, height (H, cm), and weight (W, kg) were recorded. Multiple stepwise linear regression analysis was conducted. The 124 cases were divided into 2 random groups, of which the first group was used to derive a regressive formula and the second group was used to verify the formula and compare the formula with previously published formulas.Multiple stepwise linear regression analysis showed that the important variables in estimating the depth of each kidney were the body weight (W, kg) and the total thickness (T, cm) of the body at the level of the kidneys. The important variables in estimating the depth of isthmus soft tissue and vertebral thickness were W, T, and age, W. The new formula was the following: right renal depth (cm) = 0.273 × T + 0.043 × W + 1.086 (r = 0.82, P < .05; standardized regressive coefficient: T = 0.500, W = 0.367), left renal depth (cm) = 0.245 × T + 0.041 × W + 0.676 (r = 0.83, P < .05; standardized regressive coefficient: T = 0.520, W = 0.353); isthmus depth (cm) = soft tissue depth + vertebral thickness, soft tissue depth (cm) = 0.144 × T + 0.044 × W + 0.536 (r = 0.58, P < .05; standardized regressive coefficient: T = 0.272, W = 0.335), vertebral thickness (cm) = 0.012 × age + 0.018 × W + 3.683 (r = 0.53, P < .05; standardized regressive coefficient: age = 0.326, W = 0.438). It is much better than the literatures.The new renal depth estimation formula in horseshoe kidney that we derived by using multiple stepwise linear regression has greatly outperformed other 6 previously published formulas. Isthmus depth estimation formula can also get accurate results. Our new formula provides a more reliable and accurate renal and isthmus depth estimation and contributes to improving the methods used to estimate renal function from radionuclide renography in horseshoe kidney.

Evaluation of the accuracy of renal depth estimation formulas in horseshoe kidney.

Estimation formulas are usually used to calculate renal depth when glomerular filtration rate (GFR) is measured by the Gates method. Horseshoe kidney (HSK) anatomical structure is different from the normal form of the kidney. The existing formulas are based on the normal form. It is unknown whether the existing formulas are valid in HSK patients. This study was performed to estimate the accuracy of the existing 6 renal depth estimation formulas in HSK.Renal depth and total thickness (T, cm) of the body at the level of the kidneys were measured by CT in 94 HSK patients. Their sex, age, height (H, cm), and weight (W, kg) were recorded. The existing 6 estimation formulas were used to obtain estimated renal depth. Correlation coefficients, Bland-Altman analysis, and paired t test were performed between estimated and the CT measured renal depth.Estimated renal depths were all lower than the CT measured renal depths and there was significant difference between estimated and CT measured renal depth. The CT measured renal depth and estimated renal depth derived from Ma GY formula correlated best (right: r = 0.80, P < .01; left: r = 0.77, P < .01). The renal depth derived from Tonnesen formula was significantly lower than the CT measured renal depth. The agreement between the estimated renal depth derived from Tonnesen formula and the CT measured renal depth was the worst, with the mean difference of (right: -3.11 ±â€Š1.13 cm; left: -2.79 ±â€Š1.07 cm). The agreement between the estimated renal depth derived from Li Q formula and Ma GY formula and the CT measured renal depth was the best, with the mean difference of right: -1.68 ±â€Š1.09 cm; left: -1.32 ±â€Š1.06 cm and right: -1.59 ±â€Š1.01 cm; left: -1.59 ±â€Š0.99 cm, respectively. But the greatest error of the difference between Li Q formula and Ma GY formula estimated depth and the CT measured depth was up to -4.83 cm, and the estimated deviation is unacceptable.All the existing formulas do not fully apply to HSK. To provide reliable and accurate estimates of renal depth, we should develop a new formula to estimate the renal depth in HSK patients.

Suite PET/CT neuroimaging for the diagnosis of Parkinson's disease: statistical parametric mapping analysis.

OBJECTIVES: The aim of this study was to investigate the topographical distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose metabolism in Parkinson's disease (PD) using PET/computed tomography (CT) scanning and statistical parametric mapping (SPM) analysis. PARTICIPANTS AND METHODS: Seventy-four patients (58 PD patients and 16 normal controls) underwent DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-ß-carbomethoxy-3-ß-(4-fluorophenyl) tropane (C-ß-CFT), C-raclopride (C-RAC), and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans. All three PET/CT procedures were performed in each participant. The uptake patterns were analyzed using SPM software. RESULTS: Striatal DAT binding was lower in PD patients than in controls, whereas D2 receptor binding did not differ between PD patients and controls. D2 receptor binding was increased in the putamen in only the 12 drug-naive patients. Glucose uptake was also slightly lower in the cingulate gyrus of PD patients than in the controls. CONCLUSION: Suite PET/CT scans using the ligands C-ß-CFT, C-RAC, and F-FDG PET/CT are valuable for diagnosing PD. SPM-based analysis of static PET/CT scan data is potentially of great clinical use.

Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging.

To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T- group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ±â€Š0.13 vs 0.68 ±â€Š0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ±â€Š0.21 vs 0.58 ±â€Š0.12, P = 0.002) but not in Group N (0.60 ±â€Š0.19 vs 0.55 ±â€Š0.13, P = 0.294). FLD was 0.45 ±â€Š0.17 in the T+ group and 0.60 ±â€Š0.08 in the T- group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression.

Establish New Formulas for the Calculation of Renal Depth in Both Children and Adults.

OBJECTIVE: This study was performed to develop a new formula to estimate the renal depth in both children and adults; then compare the new formula with previously published formulas. METHODS: Renal depth and total thickness (T, cm) of the body at the level of the kidneys were measured by CT in 113 children and 246 adults. Their sex, age, height (H, cm), and weight (W, kg) were recorded. Multiple stepwise linear regression analysis were conducted, using data from children and adults together. The 359 cases were divided into 2 random groups, of which, the first group was used to derive a regressive formula, and the second was used to verify the formula and compare the formula with previously published formulas in different groups. RESULTS: Multiple stepwise linear regression analysis showed that the important variable in estimating the depth of each kidney was the ratio of body weight (W, kg) to body height (H, cm) and the total thickness (T, cm) of the body at the level of the kidneys. The new formula was as follows: for right renal depth (cm) = 0.22 × T + 7.714 × W/H-0.331 (r = 0.95), and for left renal depth (cm) = 0.238 × T + 6.553 × W/H-0.618 (r = 0.95). It is better than the other four formulas in different groups, especially in children and W/H ≤ 0.30 (in adults) groups. CONCLUSIONS: We first introduced T into renal depth estimation formula and established the new formula. It has a better performance than the other four formulas in different groups. The new formula provided reliable and accurate renal depth and may contribute to improving the methods used to estimate renal function from radionuclide renography.

Can Carrier-Mediated Delivery System Promote the Development of Antisense Imaging?

PURPOSE: We aimed to explore the feasibility of transfection methods for antisense imaging. PROCEDURES: Antisense oligonucleotides (ASON) targeted to the mRNA of hTERT gene were synthesized and labeled with Technetium-99m and fluorescein isothiocyanate (FITC), respectively. Then, ASON was combined with transfection reagent Lipofectamine 2000 and Xfect(TM), named Lipo-ASON and Xfect-ASON, respectively. After transfection, the labeled ASON was characterized in hNPCs-G3 and hRPE cells. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were performed to assay the hTERT mRNA and protein levels after hNPCs-G3 cells were incubated with Lipo-ASON, Xfect-ASON, and naked ASON. In addition, Lipo-ASON, Xfect-ASON, and naked ASON were injected into tumor-bearing mice, and the biodistribution in vivo was performed. RESULTS: The presence of two transfection reagents significantly increased intracellular uptake of radiolabeled ASON in both cell lines compared with naked ASON (p < 0.05). However, there was no significant difference in cellular uptake rates of Lipo-ASON and Xfect-ASON between hNPCs-G3 and hRPE cells. In comparison with naked ASON, the fluorescence intensity was strongly enhanced after binding to transfection reagents. Furthermore, the levels of hTERT mRNA and protein were significantly reduced in cells treated with Lipo-ASON and Xfect-ASON (p < 0.05), but naked ASON had no significant effect on hTERT expression level. The biodistribution study indicated that tumor radioactivity uptake of radiolabeled ASON for naked ASON, Lipo-ASON, and Xfect-ASON group was low and shown no significant difference in vivo. CONCLUSIONS: Lipofectamine transfection and Xfect(TM) transfection were not effective delivery methods of ASON for antisense imaging.

Does the novel integrated PET/MRI offer the same diagnostic performance as PET/CT for oncological indications?

BACKGROUND: We compared PET/MRI with PET/CT in terms of lesion detection and quantitative measurement to verify the feasibility of the novel integrated imaging modality for oncological applications. METHODOLOGY/PRINCIPAL FINDINGS: In total, 285 patients referred to our PET/CT center for oncological indications voluntarily participated in this same-day PET/CT and PET/MRI comparative study. PET/CT images were acquired and reconstructed following routine protocols, and then PET/MRI was performed at a mean time interval of 28±11 min (range 15-45 min). PET/MRI covered the body trunk with a sequence combination of transverse T1WI 3D-volumetric interpolated breath-hold, T2WI turbo spin echo with fat saturation, diffusion-weighted imaging with double b values (50 and 800 s/mm2), and simultaneous PET acquisition over 45 min/5 bed positions. The maximum standardized uptake value (SUVmax) was assessed by manually drawn regions of interest over fluorodeoxyglucose-positive lesions. Among 285 cases, 57 showed no abnormalities, and 368 lesions (278 malignant, 68 benign and 22 undetermined) were detected in 228 patients. When stand-alone modalities were evaluated, PET revealed 31 and 12 lesions missed by CT and MRI, respectively, and CT and MRI revealed 38 and 61 more lesions, respectively, than PET. Compared to CT, MRI detected 40 more lesions and missed 8. In the integrated mode, PET/CT correctly detected 6 lesions misdiagnosed by PET/MRI, but was false-negative in 30 cases that were detected by PET/MRI. The overall diagnosis did not differ between integrated PET/MRI and PET/CT. SUVmax for lesions were slightly higher from PET/MRI than PET/CT but correlated well (ρ = 0.85-0.91). CONCLUSIONS/SIGNIFICANCE: The novel integrated PET/MRI performed comparatively to PET/CT in lesion detection and quantitative measurements. PET from either scanner modality offered almost the same information despite differences in hardware. Further study is needed to explore features of integrated PET/MRI not addressed in this study.

Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral µ-opioid receptor availability in rhesus monkeys.

Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real-time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on µ-opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95-min positron emission tomography (PET) with (11) C-carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95-min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy.

A study of the metabolism of transplanted tumor in the lung by micro PET/CT in mice.

The difference of tumor metabolism from that of normal tissue is an important factor for diagnosis through functional imaging such as positron emission tomography (PET). A quantitative description of the metabolic process will help to improve the diagnosis methods. In this study, the metabolism of tumor in lung was quantitatively described in mice. The melanoma was transplanted into the lung of mice, and the metabolism of the transplanted tumor was detected by micro PET/CT with [(18)F]fluoro-2-deoxy-D-glucose (FDG). Nine mice were transplanted with B16 melanoma cells through their tail vein. Lung tumor was detected by pathological method. The lesions smaller than 1mm could hardly be directly detected directly by micro PET/CT, while the tumor with a 1-4mm diameter could be detected by micro PET/CT. A metabolic model with three compartments was separately established for lung tumors and normal lung tissues. In this model, the lung cancer had a significantly higher metabolic rate constant as compared to that of the normal lung tissue (p=0.01). The outputs of the model fit well with the original curve from the dynamic images. It is also found that difference of tissue activity between tumors and normal lung tissues varied along scan time. Through this comparison, it was suggested that the difference in metabolism between the lung tissue and the tumor might contribute to the tumor diagnosis.

Standardized uptake value based evaluation of lymphoma by FDG and FLT PET/CT.

Although (18) F-FDG PET/CT imaging is the conventional method for evaluating lymphoma, PET/CT imaging with radiopharmaceuticals other than FDG is being investigated. We evaluated the utility of different standardized uptake value (SUV) measurements in (18) F-FLT PET/CT scans compared with PET/CT scans performed with FDG. Two scans, each using one of the radiopharmaceuticals, were performed on each of 114 patients with histologically proven lymphoma. Maximum and mean SUV (SUV(max)) and (SUV(mean)) of all visualized lesions, with backgrounds of mediastinal blood pool, liver, spleen and vertebra were calculated. The ratios of the SUVs of the lesions to those of each reference region were statistically analyzed. Using receiver operating characteristic curves, we analyzed the differences in uptake of the two agents in aggressive and indolent B-cell non-Hodgkin lymphoma. We found that the SUV(max) measurements of FDG were significantly different between aggressive and indolent B-cell non-Hodgkin lymphoma. The receiver operating characteristic curve of SUV(max) of tumour/liver for FDG studies resulted in the most area under the curve. The SUV(max) of the tumour/mediastinum ratio for FLT studies resulted in the most area under the curve (0.781). There was no significant correlation between FDG and FLT uptake in most types of lymphoma we studied. Further studies of the characteristics of (18) F-FLT should employ the tumour/mediastinum SUV(max) ratio for accurate uptake measurement.

[Validation of standardized uptake values for ¹8F-FDG in normal organs: comparison of whole-body PET/CT and PET/MRI].

OBJECTIVE: To validate whether PET/MR could provide a semi-quantitative measurement (SUV(max)) comparable to that produced by PET/CT in normal organs. METHODS: 277 subjects underwent an ordinary ¹8F-FDG PET/CT followed by a PET/MR scan with a 25-45 min interval. Region of interest (ROIs) were drawn in 4 reference normal organs/tissues in both MRAC-PET and CTAC-PET images and the liver and erector spinae in the dual-time point PET/CT images. RESULTS: 259 malignant and 21 benign lesions, pathologically confirmed, were detected in the 220 subjects. SUV(max) derived from PET/CT (SUV(max)-CT) and PET/MR (SUV(max)-MRI) was highly correlated over the reference organ ROIs (r = 0.62-0.73), except lung (r = 0.44). The SUV(max)-MRI was significantly lower than the respective SUV(max)-CT in all 4 organs and after delay-correction in liver and muscle. CONCLUSION: The results indicate that PET/MR can provide reliable measurement in physiological organs.

[Assessment of hepatic reserve function of cirrhosis liver using dynamic SPECT (99m)Tc-galactosyl human serum albumin scintigraphy].

OBJECTIVE: To evaluate the effectiveness of dynamic SPECT (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy on the assessment of reserve function of cirrhosis liver. METHODS: From January 2010 to December 2011, 55 patients with cirrhosis liver were enrolled in this study. The case numbers of male and female were 43 and 12 respectively and the age was (51 ± 9) years (ranging from 35 to 69 years). After routine biochemistry test, CT scan and (99m)Tc-GSA dynamic SPECT scan were performed in turn using a juxtaposed SPECT/CT system. Then the morphologic volume of liver parenchyma (MLV), functional liver volume (FLV) and the hepatic cell absorption rate constant (GSA-K) were calculated. The correlations between GSA-K and routine biochemistry test, Child-Pugh score, indocyanine green clearance rate (ICG-K) were analyzed. The patients were further divided into 3 groups according to whether there was occlusion or stenosis in the main branch of left portal vein (group 1, n = 5), right portal vein (group 2, n = 13) or not (group 3, n = 37) and the regional hepatic functions index of the 3 groups were compared. RESULTS: The value of FLV of the whole, left and right liver was (594 ± 152) ml, (244 ± 119) ml and (356 ± 171) ml, respectively. There were correlations between GSA-K and total bilirubin, prothrombintime, Child-Pugh score and ICG-K (r = -0.730--0.298, P < 0.05). The FLV and MLV ratios of involved hemiliver to uninvolved hemiliver were 0.09 ± 0.06 and 0.30 ± 0.14 in group 1, 0.57 ± 0.43 and 1.08 ± 0.63 in group 2, 0.71 ± 0.30 and 0.71 ± 0.48 in group 3. The difference in MLV-FLV ratio was signifcant between group 1 and group 3, between group 2 and group 3 (P = 0.000). CONCLUSIONS: The dynamic SPCECT (99m)Tc-GSA scintigraphy can not only assess the whole liver function of cirrhosis liver effectively, but also evaluate the variation of regional liver function accurately.

Evaluation of ¹8F-FDG and ¹8F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy.

In order to compare the efficacy of (18)F-fluorothymidine (FLT) and (18)F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P<0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P<0.001). Although increased apoptosis was observed in both cell lines after irradiation (P<0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin ß3, Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P<0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of (18)F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced (18)F-FDG uptake was only observed after 72 h. Therefore, we conclude that (18)F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells.

Can multimodality imaging using 18F-FDG/18F-FLT PET/CT benefit the diagnosis and management of patients with pulmonary lesions?

PURPOSE: Dual-tracer, (18)F-fluorodeoxyglucose and (18)F-fluorodeoxythymidine ((18)F-FDG/(18)F-FLT), dual-modality (positron emission tomography and computed tomography, PET/CT) imaging was used in a clinical trial on differentiation of pulmonary nodules. The aims of this trial were to investigate if multimodality imaging is of advantage and to what extent it could benefit the patients in real clinical settings. METHODS: Seventy-three subjects in whom it was difficult to establish the diagnosis and determine management of their pulmonary lesions were prospectively enrolled in this clinical trial. All subjects underwent (18)F-FDG and (18)F-FLT PET/CT imaging sequentially. The images were interpreted with different strategies as either individual or combined modalities. The pathological or clinical evidence during a follow-up period of more than 22 months served as the standard of truth. The diagnostic performance of each interpretation and their impact on clinical decision making was investigated. RESULTS: (18)F-FLT/(18)F-FDG PET/CT was proven to be of clinical value in improving the diagnostic confidence in 28 lung tumours, 18 tuberculoses and 27 other benign lesions. The ratio between maximum standardized uptake values of (18)F-FLT and (18)F-FDG was found to be of great potential in separating the three subgroups of patients. The advantage could only be obtained with the full use of the multimodality interpretation. Multimodality imaging induced substantial change in clinical management in 31.5% of the study subjects and partial change in another 12.3%. CONCLUSION: Multimodality imaging using (18)F-FDG/(18)F-FLT PET/CT provided the best diagnostic efficacy and the opportunity for better management in this group of clinically challenging patients with pulmonary lesions.

Monitoring early responses to irradiation with dual-tracer micro-PET in dual-tumor bearing mice.

AIM: To monitor the early responses to irradiation in primary and metastatic colorectal cancer (CRC) with (18)F-fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-FDG) small-animal position emission tomography (micro-PET). METHODS: The primary and metastatic CRC cell lines, SW480 and SW620, were irradiated with 5, 10 and 20 Gy. After 24 h, the cell cycle phases were analyzed. A dual-tumor-bearing mouse model of primary and metastatic cancer was established by injecting SW480 and SW620 cells into mice. micro-PET with (18)F-FLT and (18)F-FDG was performed before and 24 h after irradiation with 5, 10 and 20 Gy. The region of interest (ROI) was drawn over the tumor and background to calculate the ratio of tumor to non-tumor (T/NT) in tissues. Immunohistochemical assay and Western blotting were used to examine the levels of integrin ß(3,) Ki-67, vascular endothelial growth factor receptor 2 (VEGFR2) and heat shock protein 27 (HSP27). RESULTS: The proportion of SW480 and SW620 cells in the G(2)-M phase was decreased with an increasing radiation dose. The proportion of SW480 cells in the G(0)-G(1) phase was increased from 48.33% ± 4.55% to 87.09% ± 7.43% (P < 0.001) and that of SW620 cells in the S-phase was elevated from 43.57% ± 2.65% to 66.59% ± 7.37% (P = 0.021). In micro-PET study, with increasing dose of radiation, (18)F-FLT uptake was significantly reduced from 3.65 ± 0.51 to 2.87 ± 0.47 (P = 0.008) in SW480 tumors and from 2.22 ± 0.42 to 1.76 ± 0.45 (P = 0.026) in SW620 tumors. (18)F-FDG uptake in SW480 and SW620 tumors was reduced but not significantly (F = 0.582, P = 0.633 vs F = 0.273, P = 0.845). Dose of radiation was negatively correlated with (18)F-FLT uptake in both SW480 and SW620 tumors (r = -0.727, P = 0.004; and r = -0.664, P = 0.009). No significant correlation was found between (18)F-FDG uptake and radiation dose in SW480 or SW620 tumors. HSP27 and integrin ß(3) expression was higher in SW480 than in SW620 tumors. The T/NT ratio for (18)F-FLT uptake was positively correlated with HSP27 and integrin ß(3) expression (r = 0.924, P = 0.004; and r = 0.813, P = 0.025). CONCLUSION: (18)F-FLT is more suitable than (18)F-FDG in monitoring early responses to irradiation in both primary and metastatic lesions of colorectal cancer.

Using dual-tracer PET to predict the biologic behavior of human colorectal cancer.

UNLABELLED: (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) have been proven useful in diagnosing and staging many types of cancer but with emphasis on different aspects of tumor biology. The aim of the current study was to evaluate whether (18)F-FDG and (18)F-FLT can be used complementarily in monitoring the biologic characteristics of colorectal cancer (CRC). METHODS: Human CRC cell lines SW480 and SW620 of the same genetic origin but different metastatic potential were cultured and implanted into nude mice to create CRC models. Uptake of (18)F-FDG and (18)F-FLT in SW480 and SW620 cells in vitro was assessed after incubation with radiotracers for 0, 30, 60, 90, and 120 min. In vivo imaging of SW480 and SW620 tumor-bearing mice was performed using small-animal PET/CT at 60 min after injection of each tracer. A region of interest was drawn over tumor and background to calculate the tumor-to-nontumor ratio (T/NT) using software on reconstructed images. Tumor growth rate, metastatic status, and survival time were assessed in tumor-bearing mice. The relationship between uptake of the tracers, metastatic capability, and tumor marker expression was evaluated using linear regression. RESULTS: SW480 tumors grew more quickly than SW620 tumors (t = 3.332, P = 0.004). A higher incidence of lung and liver metastases was noted for SW480 than for SW620 (P = 0.023). Uptake in SW480 and SW620 cells was significantly different between (18)F-FDG and (18)F-FLT (t = 2.507, P = 0.021, vs. t = 3.497, P = 0.002). In the small-animal PET study, the T/NT of (18)F-FDG did not differ between SW480 and SW620 tumors (2.69 +/- 0.98 vs. 3.09 +/- 1.26, P = 0.524), but the T/NT of (18)F-FLT differed significantly between SW480 and SW620 tumors (3.65 +/- 0.51 vs. 2.22 +/- 0.42, P < 0.001). Heat shock protein 27 (HSP27) expression and integrin beta(3) expression were higher, whereas vascular endothelial growth factor receptor 2 (VEGFR2) expression and Ki67 expression were lower, in SW480 cells than in SW620 cells. For SW480, metastases in lung and liver correlated significantly with (18)F-FLT uptake in tumors (r = 0.763, P = 0.005) and with expression of HSP27 (r = 0.894, P = 0.008) and integrin beta(3) (r = 0.635, P = 0.088). A correlation was also found between (18)F-FLT uptake and expression of HSP27 (r = 0.924, P = 0.004) and integrin beta(3) (r = 0.813, P = 0.025). No correlation was found between (18)F-FDG uptake in tumors and metastasis in lung and liver (r = -0.111, P = 0.388). However, there was a significantly negative correlation between (18)F-FDG uptake and the survival time of tumor-bearing mice (r = -0.500, P = 0.017), to which (18)F-FLT did not relate (r = 0.262, P = 0.182). CONCLUSION: High uptake of (18)F-FDG and (18)F-FLT may reflect poorer survival and a higher metastatic potential for CRC in mice. Combining (18)F-FDG with (18)F-FLT PET would be helpful in better predicting the biologic behavior of CRC.