Validation of laser scanning confocal microscopy as a diagnostic method for lymphedema using a rat model.

Most previous diagnostic methods for lymphedema are invasive. Laser scanning confocal microscopy (LSCM) combines laser and computer image processing technology, is capable of increasing the resolution of optical microscopy by 30-40%, and boasts a comparable resolution to that of histological examination. We constructed the rat tail lymphedema model to simulate secondary lymphedema and to validate the noninvasive technique of in vivo reflectance LSCM for the diagnosis of lymphedema. The rat tail lymphedema model was constructed by cutting and ligating the lymphatic vessels in the rat tail. Lymphedema in the postoperative rat tail was assessed by a comprehensive range of methods including the change of rat tail diameter, lymphocytic radionuclide imaging, LSCM, and immunohistochemistry using a specific lymphatic vessel marker, prospero homeobox protein 1 (PROX1). The noninvasive LSCM method along with other techniques validated the rat tail lymphedema model. LSCM was used to perform qualitative and quantitative evaluation of the state and extent of lymphedema in the rat tail model. Receiver operating characteristic (ROC) curve analysis, which provided an area under the curve (AUC) value of 0.861, supported the feasibility of using LSCM as a reliable diagnostic technique for lymphedema. The rat tail lymphedema model can be successfully constructed by cutting and ligating the lymphatic vessels in the rat tail. Although LSCM cannot replace the method of skin biopsy examination, it offers a painless and noninvasive alternative for diagnosing lymphedema. Thus, LSCM can potentially be adopted in clinical practice as a supporting method to be used in combination with other techniques.

Correlation of hypoxia as measured by fluorine-18 fluoroerythronitroimidazole (18F-FETNIM) PET/CT and overall survival in glioma patients.

PURPOSE: Hypoxia is important in the biology of glioma in humans. Positron emission tomography/computed tomography (PET/CT) with a hypoxia tracer offers a noninvasive method to differentiate individual tumor biology and potentially modify treatment for patients with malignancies. The purpose of this study was to determine whether hypoxia, as measured by fluorine-18 fluoroerythronitroimidazole (18F-FETNIM) PET/CT, was associated with tumor grade, overall survival (OS), and immunohistochemical features related to hypoxia, proliferation, angiogenesis, and the invasion of gliomas. PROCEDURES: Twenty-five patients with gliomas in whom gross maximal resection could be safely attempted were analyzed. All patients underwent 18F-FETNIM PET/CT studies before surgery. The maximum standardized uptake value (SUVmax) was obtained from the PET images of tumor tissues. Tumor specimens were stereotactically obtained for the immunohistochemical staining of hypoxia-inducible factor-1 alpha (HIF-1α), Ki-67, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9). RESULTS: A correlation between the SUVmax and glioma grade was found (r = 0.881, P < 0.001). The SUVmax was significantly correlated with the expression of HIF-1α, Ki-67, VEGF, and MMP-9 (r = 0.820, 0.747, 0.606, and 0.727; all P < 0.001). Patients with a high SUVmax had significantly worse 3-year OS than those with a low SUVmax (24.4% vs. 82.1%, P = 0.003). CONCLUSIONS: 18F-FETNIM PET/CT provides an excellent noninvasive assessment of hypoxia in glioma. It can be used to understand the mechanisms by which hypoxia affects the OS of glioma patients.

[Internal mammary sentinel lymph node biopsy in breast cancer: accurate staging and individualized treatment].

OBJECTIVE: The aim of this study was to determine the impact of routinely performed internal mammary sentinel lymph node biopsy (IM-SLNB) on the staging and treatment, and to analyze the success rate, complications and learning curve. METHODS: All patients with biopsy-proven breast cancer who underwent sentinel lymph node biopsy between 2012 and 2014 were included in a prospective analysis. Internal mammary sentinel lymph node biopsy (IM-SLNB) was performed in all patients with IM-SLN visualized on preoperative lymphoscintigraphy and/or detected by intraoperative gamma probe detection. The adjuvant treatment plan was adjusted according to the current guidelines. RESULTS: In a total of 349 patients, 249 patients (71.1%) showed internal mammary drainage. IM-SLNB was performed in 153 patients with internal mammary drainage, with a success rate of IM-SLNB of 97.4% (149/153). Pleural lesion and internal mammary artery bleeding were found in 7.2% and 5.2% patients, respectively. In 8.1% of patients (12/149) the IM-SLN was tumor positive. In the group of patients who underwent IM-SLNB, lymph node staging was changed in 8.1% of patients, and IMLNs radiotherapy was guided by these results, however, systemic treatment was changed in only 0.7% of the patients. CONCLUSIONS: IM-SLNB has a high successful rate and good safety. Identification of internal mammary metastases through IM-SLNB may provide more accurate staging and guide the tailored internal mammary radiotherapy. TRIAL REGISTRATION: ClinicalTrials. gov, NCT01642511.

[A novel technique for scintigraphic visualization of internal mammary sentinel lymph nodes in breast cancer patients].

OBJECTIVE: To explore the effects of different injection techniques of radiotracer on the visualization rate of internal mammary sentinel lymph nodes (IMSLN) in breast cancer patients. METHODS: A series of 137 consecutive breast cancer patients was included in this prospective study. Fifty-eight patients (group A) received the radiotracer (99)Tc(m)-sulphur colloid injected only into 1-2 points in the breast parenchyma in one quadrant, and seventy-nine patients (group B) received the radiotracer injection into the breast parenchyma in two quadrants of the breast. The differences of IMSLN visualization rates of the two groups were compared and the relevant affecting factors were analyzed. RESULTS: The IMSLN visualization rate of the group B (70.9%, 56/79) was significantly higher than that of the group A (13.8%, 8/58) (P < 0.001). Both techniques seemed to be reliable to identify sentinel lymph node in the axilla (98.7% vs. 98.3%, P = 0.825). In addition, the visualization rate of internal mammary hotspots (82.2%) was more commonly seen in patients receiving injection of a larger volume of radiotracer ( ≥ 0.5 ml/point) than those receiving a smaller volume of radiotracer (<0.5 ml/point, 55.9%, P = 0.011). CONCLUSIONS: The modified injection technique (two quadrants, large volume radiotraver, and ultrasound guidance) can significantly improve the visualization rate of IMSLN. Our findings should make the biopsy of IMSLN widely implemented and provide an effective and minimally invasive technique to evaluate the internal mammary lymph node status.

Risk factors for sentinel lymph node metastasis and validation study of the MSKCC nomogram in breast cancer patients.

OBJECTIVE: To evaluate the risk factors for sentinel lymph node metastasis and validate the value of the Memorial Sloan-Kettering Cancer Center nomogram for the prediction of sentinel lymph node metastasis in breast cancer patients. METHODS: A sentinel lymph node biopsy database containing 1227 consecutive breast cancer patients (416 patients with at least one positive sentinel lymph node) was retrospectively analyzed. The predictive value of the Memorial Sloan-Kettering Cancer Center nomogram was calculated by the trend line and the area under the receiver-operator characteristic curve. Meanwhile, predictors for sentinel lymph node metastasis were also evaluated. RESULTS: Tumor size, histological grade, lymphovascular invasion, mulifocality, estrogen receptor and progesterone receptor status were significant independent predictors for sentinel lymph node metastasis (all P<0.01). The Memorial Sloan-Kettering Cancer Center nomogram presented an area under the receiver-operator characteristic curve value of 0.730. Patients with predictive value<16% had a frequency of sentinel lymph node metastasis of 0.9%. Those with values larger than 70% had a frequency of 96.2%. CONCLUSIONS: The risk factors for sentinel lymph node metastasis in our study were consistent with those in the Memorial Sloan-Kettering Cancer Center nomogram. The Memorial Sloan-Kettering Cancer Center nomogram is a useful tool that could accurately predict the probability of sentinel lymph node metastasis in our breast cancer patients. Axillary surgical staging might be avoided in patients with a predictive value of <16% and axillary lymph node dissection might be done directly in those with a predictive value >70%, while other patients should still accept sentinel lymph node biopsy.

18F-FDG PET/CT imaging in the diagnosis of drug-induced lung disease and pulmonary infection in lymphoma.

OBJECTIVE: Lymphoma is a hematological disease with high prevalence. Multi-cycle chemotherapy (CHT) or local radiotherapy is applied usually; however, adverse events have been reported, such as drug-induced lung disease (DILD). Positron emission tomography/computed tomography (PET/CT) is often used to evaluate the lesion, treatment effect, and prognosis of lymphoma. We investigated DILD and pulmonary infection (PI) after multi-cycle CHT in lymphoma patients, to identify DILD and PI, provide guidance for later treatment for them. METHODS: In all, 677 patients diagnosed with lymphoma and who underwent CHT were included. These patients underwent 18fluorodeoxyglucose (18F-FDG) PET/CT before and after CHT at Shandong Cancer Hospital (affiliated with Shandong University) between April 2015 and November 2019. Fifty patients developed DILD, 41 patients had lung infections; lesion characteristics were analyzed based on clinical characteristics, laboratory examinations, and PET/CT imaging. RESULTS: Among the 677 lymphoma patients, there were 50 cases of DILD, with an incidence rate of 7.4%. PET/CT showed an elevated 18fluorodeoxyglucose uptake lung background, septal thickening and reticulation, multiple ground glass-like shadows, and grid-shaped blur shadows, which were more common in the lung periphery and under the pleura. The maximum standardized uptake value in the lung was 2.45 ±â€Š0.52. Pulmonary infections occurred in 41 patients, and the maximum standardized uptake value was 4.05 ±â€Š1.42. Age, sex, CHT cycle, Ann-Arbor stage, and lymphocyte levels were not significantly different between DILD and PI patients. Leukocyte and neutrophils showed significant differences; the PI patients had increased laboratory indexes of leukocyte and neutrophils. The mean number of CHT cycles was 4 cycles for DILD and PI. CONCLUSIONS: PET/CT imaging has high sensitivity and detection rates for primary and metastatic lymphoma lesions. DILD mostly occurs in the middle and late stages of CHT. Laboratory tests and PET/CT can evaluate the lesions and treatment effects, and provide guidance for subsequent treatment plans for patients.

Roles of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer patients.

OBJECTIVE: To evaluate roles of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer patients. METHODS: Five hundred and sixty-five consecutive breast cancer patients were prospectively randomized into groups with or without preoperative lymphoscintigraphy. RESULTS: In a group with lymphoscintigraphy, 238 patients had sentinel lymph nodes spotted in lymphoscintigram. The visualization of sentinel lymph nodes in lymphoscintigram was not associated with patients' age, primary tumor size and location, histopathologic type and time interval from injection of radiocolloid to lymphoscintigraphy. However, patients with axillary metastasis had a lower identification rate of sentinel lymph nodes by lymphoscintigraphy than those without metastasis (P = 0.003). The identification rate of axillary sentinel lymph nodes was 99.3% in the group and the rate was similar whether there was sentinel lymph nodes spotted in axillary in lymphoscintigram or not (99.6% vs. 98.1%, P = 0.327). The false-negative rate in this group was 4.2%. While in a group without lymphoscintigraphy, the identification rate and the false-negative rate were 99.6% and 4.8%, respectively. There was no significant difference between the two groups in the identification rate of axillary sentinel lymph nodes (P = 0.594) and in the false-negative rate (P = 1.00). CONCLUSION: Preoperative lymphoscintigraphy could neither improve the identification rate nor reduce the false-negative rate of breast cancer sentinel lymph node biopsy, and it is not necessary for sentinel lymph node biopsy in breast cancer patients.

[Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung cancer].

OBJECTIVE: To assess the feasibility of [(18)F]fluoroerythronitroimidazole ((18)F-FETNIM) with integrated positron emission tomography and computed tomography (PET-CT) imaging in detection of hypoxia in non-small-cell lung cancer (NSCLC) patients. METHODS: Forty-two patients with newly diagnosed NSCLC underwent (18)F-FETNIM PET-CT before treatment. Nineteen patients rested for approximately 120 minutes before undergoing PET-CT, 23 patients underwent 2 sequential PET-CT scans at 60 minutes and 120 minutes after intravenous injection (18)F-FETNIM. (18)F-FETNIM uptake was quantified by calculating the maximum standardized uptake value in the tumor (SUVmax-T) and contralateral normal lung tissue (SUVmax-N). Regions of interest (ROIs) were drawn in the tumor and contralateral position and the radioactivity ratio of tumor to normal (T/N) was calculated. RESULTS: SUVmax-T (2.43 +/- 1.34) was significantly higher than SUVmax-N (0.87 +/- 0.46, P < 0.001) at 120 min. SUVmax-T (2.80 +/- 1.09) and SUVmax-N (1.16 +/- 0.56) at 60 min were significantly higher than SUVmax-T (2.61 +/- 1.10) and SUVmax-N (P < 0.01) at 120 min. T/N (2.56 +/- 0.71) at 60 min was higher than that at 120 min (2.48 +/- 0.60), but the difference between them was not significant (P = 0.324). CONCLUSION: Our results indicate that (18)F-FETNIM PET-CT may be a useful tool for evaluating hypoxia and may be a means to target specifically tumor cells resistant to conventional treatment before and during ongoing therapy in NSCLC.

PET-based biodistribution and radiation dosimetry of epidermal growth factor receptor-selective tracer 11C-PD153035 in humans.

UNLABELLED: The present study estimated the biodistribution and radiation-absorbed dose of epidermal growth factor receptor (EGFR) radioligand 11C-PD153035 in whole-body PET examinations of healthy volunteers. METHODS: Two-dimensional whole-body PET was performed on 9 subjects after injection of 11C-PD153035 at 329.3+/-77.8 MBq (mean+/-SD). A total of 12 frames were acquired for approximately 90 min in 7 segments of the body. Regions of interest were drawn on PET images of source organs. Residence time was calculated as the area under the time-activity curve. Radiation dosimetry was calculated from organ residence time by use of MIRDOSE3 software. RESULTS: The renal and hepatobiliary systems played important roles in 11C-PD153035 excretion from the body, accounting for the excretion of approximately 23% and 19% of the injected radioactivity, respectively. Blood-pool activity was only moderate and declined over time. Tracer accumulation in the lungs, bone marrow, and muscles was slight, resulting in low background activity in the chest. The organs with the highest radiation-absorbed doses were the urinary bladder and the gallbladder; the effective doses were 6.08E-02+/-1.85E-02 and 2.40E-02+/-8.01E-03 mGy/MBq, respectively. The effective dose equivalent was 7.43E-03+/-1.10E-03 mSv/MBq, and the dose-limiting organ was the urinary bladder. CONCLUSION: On the basis of the estimated absorbed dose, 11C-PD153035 displayed a favorable radiation dose profile in humans and therefore could be used in multiple PET examinations of the same subject per year. 11C-PD153035 is a promising ligand for the investigation of EGFR in humans, especially in chest tumors such as non-small cell lung cancer.

Relationship between primary tumor fluorodeoxyglucose uptake and nodal or distant metastases at presentation in T1 stage non-small cell lung cancer.

Many studies have shown that FDG uptake is related to prognosis of non-small cell lung cancer, and metastasis is the major cause of death due to lung cancer patients. However, the FDG uptake of primary tumor in relation to nodal or distant metastasis at presentation has not been studied directly. Newly diagnosed non-small cell lung cancer patients who accepted (18)F-FDG PET/CT staging in the nuclear medicine center of Shandong Cancer Hospital between 1 June 2004 and 1 October 2007 were retrospectively reviewed. One hundred and seven patients with clinical T1 stage and definited histologic or cytologic evidence were enrolled and analyzed. Significant differences were observed in primary tumor SUVmax for different stages (Stage Ia-IV, P=0.004), different N status (N(0)M(0) vs. N(1-3)M(0), P=0.008) and tumors absence any spread vs. presence distant metastasis (N(0)M(0) vs. M(1), P=0.000). Spearman rank analysis showed moderate correlations between SUVmax and different N or M status (r=0.369, P=0.000 for Stage Ia-IV; r=0.337, P=0.004 for N(0)M(0) vs. N(1-3)M(0); r=0.474, P=0.000 for N(0)M(0) vs. M(1); respectively). There was a statistically significant increase in the probability of metastases at presentation with each unit increase in SUVmax. (logistic regression model, OR=1.469; 95% CI, 1.175-1.836; P=0.001). These results suggest that FDG uptake is a potential indicator of metastases in small primary lesion of non-small cell lung cancer.

[Correlation between PET-CT 18FDG uptake in primary lesions and clinicopathological parameters in esophageal carcinoma patients].

OBJECTIVE: To investigate the correlation between 18F-fluorodeoxyglucose (18FDG) uptake of primary lesions during PET-CT (positron emission tomography and computed tomography) examination and clinicopathological parameters such as the tumor length, depth of invasion, differentiation of the primary lesions and lymph node metastasis status in the patients with esophageal carcinoma. METHODS: From June 2004 to November 2006, 68 operable esophageal carcinoma patients were enrolled into this study, and all had a whole body 18FDG PET-CT scan before operation. The maximum standardized uptake value (SUVmax) of the primary lesions was measured. The tumor length, depth of invasion, differentiation of the primary lesions and lymph node metastasis status were determined by postoperative pathological examination. The correlation between the standardized uptake value (SUV) of primary lesions and the above mentioned clinicopathological parameters was analyzed. RESULTS: The overall length of primary lesion was positively correlated with SUVmax (r=0.512, P=0.01). Depth of invasion was also positively correlated with SUVmax (r=0.860, P=0.000). There was a statistically significant difference in SUVmax between poorly differentiated group and moderately or well differentiated group (r=0.781, P=0.000), and also between the groups with or without lymph node metastasis (r=0.852, P=0.000). CONCLUSION: The tumor length, depth of invasion and differentiation of the primary lesions of the esophageal carcinoma are all positively correlated with maximum standardized uptake value of 18FDG. The more poorly differentiated lesions show a higher 18FDG maximum standardized uptake value. The lesions with lymph node metastasis have also a significantly higher 18FDG maximum standardized uptake value than those without lymph node metastases.

[Correlations of 99 Tc m-HL91 SPECT hypoxia imaging with HIF-1alpha and VEGF expression in non-small cell lung cancer].

OBJECTIVE: (99)Tc(m)-HL91 ((99)Tc(m) labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) is a potential noninvasive marker of tumor hypoxia. It has been reported that (99)Tc(m)-HL91 has validity for hypoxia imaging in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the (99)Tc(m)-HL91 SPECT hypoxia imaging of NSCLC, the expression of inducible hypoxia factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF), and to analyze their correlations with clinicopathological characteristics. METHODS: Twenty NSCLC patients who underwent radical resection were enrolled into this study prospectively. (99)Tc(m)-HL91 SPECT scanning was performed in all patients at one or two days before surgery. After intravenous injection of approximately 740 MBq (99)Tc(m)-HL91, anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively. Regions of interest (ROIs) were drawn in the tumor and the contralateral normal lung tissue, and the radioactivity ratio of tumor to normal tissue (T/N) was calculated. Immunohistochemistry was used to detect the expression of HIF-1alpha and VEGF in sequential histological sections of specimens. RESULTS: Among the 20 NSCLC patients, 13 showed positive expression of HIF-1alpha and 15 had positive expression of VEGF, with a positive rate of 65.0% and 75.0%, respectively. The uptake of (99)Tc(m)-HL91 was strongly correlated with the expression status of HIF-1alpha. No correlation between HIF-1alpha and VEGF expression levels was observed. The HIF-1alpha expression level was not correlated with histological subtype, but with lymph node involvement. The expression levels of HIF-1alpha and VEGF were positively correlated with tumor stage. CONCLUSION: The result of (99)Tc(m)-HL91 SPECT hypoxia imaging is found to be positively correlated with expression of HIF-1alpha in the non-small cell lung cancer. HIF-1alpha expression is positively correlated with VEGF expression. Furthermore, both HIF-1alpha and VEGF expressions are increasing with the increase of tumor stage.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer (99mTc-Dextran 40) in Breast.

PURPOSE: The purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast. MATERIALS AND METHODS: A small particle radiotracer (99mTc-Dextran 40) was prepared and tested. 99mTc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging. RESULTS: The radiochemical purity of 99mTc-Dextran 40 was > 95%. 99mTc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After 99mTc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then 99mTc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area. CONCLUSION: The lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Hypoxia with 18F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (18F-FETNIM PET/CT) in locoregionally advanced head and neck cancer: Hypoxia changes during chemoradiotherapy and impact on clinical outcome.

Hypoxia is a well-recognized biological characteristic to therapy resistance and negative prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). This study aims to investigate the changes of hypoxia measured by F-fluoroerythronitroimidazole (FETNIM) uptake on integrated positron emission tomography and computed tomography (PET/CT) during chemoradiotherapy and its prognostic value of clinical outcome in locoregionally advanced HNSCC.Thirty-two patients with locoregionally advanced HNSCC who received definitive treatment with concurrent chemoradiotherapy underwent FETNIM PET/CT scans before and after 5 weeks of treatment. The intensity of hypoxia using the maximum standardized uptake value (SUVmax) was evaluated both on primary lesion and metastatic lymph node (MLN). The pre-SUVmax and mid-SUVmax were defined as SUVmax on pre- and mid-FETNIM PET/CT. The local control (LC), regional control (RC), distant metastatic-free survival (DMFS), and overall survival (OS) were collected in patient follow-ups.Mid-SUVmax decreased significantly both in the primary tumor (t = 8.083, P < .001) and MLN (t = 6.808, P < .001) compared to pre-SUVmax. With a median follow-up of 54 months, the 5-year LC, RC, DMFS, and OS rates were 55%, 66.7%, 64.7%, and 55%, respectively, for all of the patients. On univariate analysis, patients with high pre-SUVmax in primary tumor had significantly worse LC (56.3% vs 87.5%, P = .046) and OS (43.8% vs 87.5%, P = .023) than other patients. Patients with high mid-SUVmax had significantly worse DMFS (50% vs 84.6%, P = .049) and OS (33.3% vs 73.1%, P = .028) than other patients. The tumor grade and mid-SUVmax were the significant predictors of OS on multivariate analysis.In this study, hypoxia in tumor significantly decreased during chemoradiotherapy. The persistent hypoxia predicted poor OS. The data provided evidence that FETNIM PET/CT could be used dynamically for selecting appropriate patients and optimal timing of hypoxia-adapted therapeutic regimens.

[(18)F-FDG PET-CT in detecting the primary tumor in patients with metastatic cancers of unknown primary origin].

OBJECTIVE: To evaluate the value of (18)F-FDG PET-CT in detecting the primary tumor in patients with metastatic cancers of unknown primary origin. METHODS: Sixty-seven patients with metastatic cancers of unknown primary origin after extensive conventional diagnostic work-up were enrolled into this study. (18)F-FDG PET-CT scans were performed at approximately 60 minutes after the intravenous injection of 7.4 MBq (18)F-FDG/kg, then delayed imaging scans was done at approximately 180 minutes for detecting the primary focus. The standardized uptake value (SUV) >or= 2.5 on standard PET/CT imaging was considered as positive. Ten percent increase of retention index (RI) was also regarded as positive. The correlation between (18)F-FDG PET-CT results and histopathological and clinical findings were analyzed, and the SUV of detected primary focus and that of metastatic cancers were compared. RESULTS: Of the 67 patients, the primary tumors were identified in 39 (53.7%) by (18)F-FDG PET-CT, and 36 of them were confirmed by pathology or follow-up. Thirteen distant metastases and seventeen lymphatic metastases were newly discovered by whole body (18)F-FDG PET-CT imaging. The SUV of metastatic tumors was significantly lower than that of primary tumors (t = 3.470,P = 0.001) and closely correlated with that of the primary tumors (r = 0.738, P = 0.000). CONCLUSION: (18)F-FDG PET-CT is not only valuable in identifying the unknown primary tumor in patients with metastatic carcinoma, but can also be used to reveal the biological characteristics of the tumors by functional imaging.

[Significance of dual-time-point 18F-FDG PET imaging in evaluation of hilar and mediastinal lymph node metastasis in non-small-cell lung cancer].

OBJECTIVE: To explore the diagnostic value of dual-time-point 18F-FDG PET-CT imaging in detecting hilar and mediastinal lymph node metastasis in non-small-cell lung cancer (NSCLC). METHODS: Forty-six patients with NSCLC underwent standard whole body single-time 18F-FDG PET-CT scans and a delayed imaging for the thorax alone before surgery, meanwhile, the standard uptake value (SUV) and retention index (RI) were calculated. RESULTS: A total number of 584 lymph nodes were excised in the 46 patients. Of these, 134 metastatic lymph nodes were pathologically confirmed in 31 patients. There were 189 lymph nodes detected and suspected to be metastatic by standard single-time 18 F-FDG PET-CT imaging, and 161 by dual-time-point imaging. Therefore, the sensitivity, specificity, diagnostic accuracy, positive predictive value and negative predictive value in the detection of hilar and mediastinal lymph node metastasis were 87.3%, 84.0%, 84.8%, 61.9% and 95.7% by standard single-time 18F-FDG PET-CT imaging, versus 94.8%, 92.2%, 92.8%, 78.9% and 98.1%, respectively, by dual-time-point imaging. There was a statistically significant difference in the detection of lymph node metastasis between the standard single-time imaging and dual-time-point 18F-FDG PET-CT imaging. CONCLUSION: Dual-time-point 18F-FDG PET-CT imaging is more sensitive, specific and accurate than standard single-time 18F-FDG PET-CT imaging in the detection of hilar and mediastinal lymph node metastasis, and may provide more information for diagnosis, staging and treatment of non-small cell lung cancer.

[Molecular imaging of epidermal growth factor receptor in glioma-bearing rats].

OBJECTIVE: To investigate the value of 11C-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat. METHODS: The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography (PET/CT) scans started as soon as intravenous injection of 11C-PD153035 (15-20 MBq/0.3 ml) was completed, images were collected continuously. The region of interest (ROI) was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed. RESULTS: There were significant differences in 11C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order: liver > gastrointestinal tract > kidney > lung > brain > muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio (T/NT, target/non-target) peaked (4.15) at 40 - 50 min post injection. The in vitro blocking study showed that 11C-PD153035 uptaken by C6 cells could be blocked by PD153035. CONCLUSION: The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors. 11C-PD153035 has a potential as a bioprobe to yield useful information for both diagnosis and therapy of tumors. However, the high concentration of 11C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.

The value of 18F-FDG PET/CT in patient with neurofibromatosis type 1: A case report and literature review.

RATIONALE: Neurofibromatosis type one (NF1) is characterized by cutaneous and nervous lesions, and the tendency to form plexiform neurofibromas (PNFs). PNFs may undergo malignant transformation into a malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs often carry an significant morbidity and mortality. PATIENT CONCERNS: A 17-year-old man with gradually increased multiple subcutaneous soft lesions. He also presented with numerous lentigines and multiple café-au-lait macules on his body. DIAGNOSES: These were collagen neurofibroma, which were definitively diagnosed by pathology. NF1 was eventually diagnosed. INTERVENTIONS: These lesions were abnormal uptake of radiotracer, when he underwent positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) scanning. Standard uptake value (SUV) and other parameters can help to distinguish benign and malignant lesions in patient with NF1. He was underwent serials F-FDG PET/CT examinations to followed up, in order to monitor these lesions malignant transformation. OUTCOMES: So far, these subcutaneous soft lesions were not malignant transformation. LESSONS: F-FDG PET/CT is being increasingly used as an imaging modality to discover the systemic lesions and to discriminate between benign and malignant plexiform neurofibromas.

Comparison of predictive powers of functional and anatomic dosimetric parameters for radiation-induced lung toxicity in locally advanced non-small cell lung cancer.

PURPOSE: To investigate the predictive value of the perfusion (Q) single-photon emission computed tomography (SPECT)-weighted dose-function histogram (DFH) obtained mid-treatment (mid-Tx) with radiotherapy (RT) for radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study population consisted of NSCLC patients who were undergoing RT treatment and enrolled in prospective imaging studies. Q-SPECT was performed prior to and during RT (at ∼40-45 Gy). A baseline dose-volume histogram (DVH) and mid-Tx DVH based on simulation CT as well as a baseline DFH and mid-Tx DFH based on Q-SPECT were calculated. Only patients with stage III NSCLC and visible functional lung (FL) changes on the mid-Tx scan were eligible for this enriched analysis. RILT was graded according to a reported scale. RESULTS: Forty-two stage III NSCLC patients met the criteria for inclusion. The accumulative incidence of grade ≥2 RILT was 31% in this high-risk population. Significant differences in functional metrics such as functional lung volume FV5-FV20 at increments of 5 Gy and functional MLD (FMLD) were observed between patients with and without grade ≥2 RILT (p < 0.05). Similar results were also obtained for anatomical metrics from V5-V20 and MLD (p < 0.05). The areas under the receiver operating characteristic curves (AUCs) ranged from 0.724to 0.812 for baseline DVH parameters, from 0.745 to 0.830 for mid-Tx DVH parameters, from 0.764 to 0.878 for baseline DFH parameters, and from 0.767 to 0.891 for mid-Tx DFH parameters. Further principal components analysis showed that the AUCs were 0.814/0.817 and 0.790/0.857 for baseline/mid-Tx DVH and baseline/mid-Tx DFH, respectively. CONCLUSIONS: Mid-Tx DFH parameters based on Q-SPECT were significantly elevated in patients with grade ≥2 RILT in this study population. Among the metrics compared, mid-Tx DFH seemed to have better predictive accuracy, but this difference did not reach statistical difference.