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.

Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique: High Visualization Rate and Accurate Staging.

Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns because of the low visualization rate of internal mammary sentinel lymph nodes (IMSLN) with the traditional radiotracer injection technique. In this study, various injection techniques were evaluated in term of the IMSLN visualization rate, and the impact of IM-SLNB on the diagnostic and prognostic value were analyzed.Clinically, axillary lymph nodes (ALN) negative patients (n = 407) were divided into group A (traditional peritumoral intraparenchymal injection) and group B (modified periareolar intraparenchymal injection). Group B was then separated into group B1 (low volume) and group B2 (high volume) according to the injection volume. Clinically, ALN-positive patients (n = 63) were managed as group B2. Internal mammary sentinel lymph node biopsy was performed for patients with IMSLN visualized.The IMSLN visualization rate was significantly higher in group B than that in group A (71.1% versus 15.5%, P < 0.001), whereas the axillary sentinel lymph nodes were reliably identified in both groups (98.9% versus 98.3%, P = 0.712). With high injection volume, group B2 was found to have higher IMSLN visualization rate than group B1 (75.1% versus 45.8%, P < 0.001). The IMSLN metastasis rate was only 8.1% (12/149) in clinically ALN-negative patients with successful IM-SLNB, and adjuvant treatment was altered in a small proportion. The IMSLN visualization rate was 69.8% (44/63) in clinically ALN-positive patients with the IMSLN metastasis rate up to 20.5% (9/44), and individual radiotherapy strategy could be guided with the IM-SLNB results.The modified injection technique (periareolar intraparenchymal, high volume, and ultrasound guidance) significantly improved the IMSLN visualization rate, making the routine IM-SLNB possible in daily practice. Internal mammary sentinel lymph node biopsy could provide individual minimally invasive staging, prognosis, and decision making of the internal mammary radiotherapy, especially for clinically ALN-positive patients.

[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.

[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.

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.

[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.

[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.

[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.

[(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.

[Preliminary study of 18F-FDG PET-CT in defining lymph node radiation target volume for non-small-cell lung cancer patients].

OBJECTIVE: To investigate the value of 18F-FDG PET-CT in detecting metastatic lymph node and radiation planning for patient with non-small-cell lung cancer (NSCLC). METHODS: The data of 58 NSCLC patients were retrospectively analyzed. Preoperatively, Both 18F-FDG PET-CT and CT scan were performed for all patients. Blinded interpretation of these images was then carried out. The gross tumor volume defined by radiation oncologist based on imaging results of either PET-CT or CT alone was compared with pathological results eventually. RESULTS: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of detecting metastatic lymph node in the mediastinum was 56.0%, 54.2%, 54.8%, 38.9%, 70.3% by CT alone, and 88.0%, 85.4%, 86.3%, 75.9%, 93.2% by PET-CT, respectively. There was a statisticalty significant difference between two methods(P < 0.05). However, statisticalty no significant difference in detecting hilar lymph nodes was observed. The radiation target volume defined by CT was identical to that by PET-CT in 31(53.5%) cases, but changed in the other 27 (46.5%) cases when 18F-FDG PET data was added. The accuracy was 75.9% in detecting metastatic lymph nodes in the radiation target volume defined by PET-CT, while it was much lower by CT alone (48.3%) with a statistically significant difference between two methods (P < 0.05). CONCLUSION: 18F-FDG PET-CT is more accurate than CT alone in assessment of mediastinal lymph nodes for NSCLC patients. It may be recommended as a method in defining the radiation target volume.

Further characterization of the epidermal growth factor receptor ligand 11C-PD153035.

BACKGROUND: (11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels. METHODS: Synthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter. RESULTS: Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001). CONCLUSIONS: The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.

[FDG PET/CT versus PET alone for pre-surgical detection of lymph node metastasis in esophageal carcinoma].

OBJECTIVE: To compare the combined FDG PET/CT with PET alone in the detection of lymph node metastasis (LNM) for esophageal carcinoma patient. METHODS: From November 2003 to August 2005, 35 patients with esophageal carcinoma underwent FDG PET/CT before esophagectomy and lymph node (LN) dissection. The patients who had history of previous anticancer treatment or diabetes mellitus and inflammatory lung diseases as well as being inoperable for medical reasons were excluded. The results of LNM detection by PET/CT and PET alone were compared with pathological results. RESULTS: Twenty-nine men and 6 women were eligible for this study, with a mean age of 57 years (range: 40 to 72 years). Of these 35 patients, 3 had lesion at the upper third thoracic esophagus, 22 at the middle third and 10 at the lower third. All patients underwent surgical resection successfully. Twenty-five patients and 65 out of 313 excised nodal groups were found to have metastases by pathological examination. The true positive and true negative LNM interpretation reached 61 and 229 LN groups on PET/CT versus 53 and 217 LN groups on PET alone. False negative LNM interpretation was found in 12 LN groups on PET alone, and 8 of them were corrected by PET/CT including one cervical LN, 4 paraesophageal LNs, one left gastric arterial LN, one left gastric cardia LN, one lesser gastric curve LN. False positive interpretations on PET alone were found in 31 LN groups, 12 of them were corrected by PET/CT which included 9 false-positive interpretations due to physical tracer uptake (2 in the cervical region and 7 in gastrointestinal tract ) and 3 lesions with heterogeneous tracer uptake in the primary tumor. The sensitivity, specificity and accuracy of LNM detection by PET alone was 81.54% (53/65), 87.50% (217/248), and 86.26% (270/313), whereas by PET/CT, which was 93.85% (61/65), 91.24% (229/248) and 92.65% (290/313), respectively. There were statistically significant differences in sensitivity and accuracy of LNM detection between PET/CT and PET alone (0.033 and 0.009). CONCLUSION: Compared with FDG PET alone, FDG PET combined with CT can improve the sensitivity and accuracy in detection of lymph node metastasis in esophageal carcinoma.

[Prognostic value of 9mTc-HL91 SPECT hypoxia imaging in patients with advanced NSCLC].

OBJECTIVE: Tumor hypoxia can influence response to radiotherapy and other treatment modalities. Oxygenation status is proved to be an independent prognostic factor. 99mTc-HL91 (99mTc 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 99mTc-HL91 has certain validity for hypoxia imaging. But its clinical study had not been reported widely. This study was carried out to evaluate the relationship between the T/N ratio of HL91 SPECT hypoxia imaging and the radiotherapeutic outcome. METHODS: 32 patients with pathologically proven non-small cell lung cancer received three-dimensional conformal radiotherapy were enrolled into the study. 99mTc-HL91 SPECT scanning was performed in all patients at one or two days before radiotherapy. It was also performed in 18 patients at one or two days after the onset of radiotherapy, when they received a dose of 30 - 40 Gy already. Anterior, posterior and lateral planar images were collected at 2, 4 and 6 hours, respectively, after intravenous injection of approximately 740 MBq 99mTc-HL91. 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. To assess whether the tumor uptake of 99mTc-HL91 is predictive of treatment response, the SPECT results were correlated with the results of clinical follow-up. RESULTS: The relationship between T/N ratios at 4 h images after injection was shown to be the best of three acquired images before radiotherapy. The response and overall survival to radiotherapy were analyzed for all 32 patients. The results of 9mTc-HL91 correlated well with radiotherapy response (P = 0. 002) and also patients' survival (P = 0.043). The average T/N values of 18 patients who received serial scanning were 1.57 +/- 0.18, 1.44 +/- 0.19 and 1.30 +/- 0.14, respectively. There was a significant difference between those three groups (P = 0. 000). The T/N changes during radiotherapy were not associated with the treatment outcome. CONCLUSION: HL91 SPECT imaging can identify the hypoxia status and changes during radiotherapy in lung cancer. Hypoxia SPECT imaging with HL91 before treatment may predict radiotherapy response and patients' survival. Longer follow up in more patients is planned to confirm this result.

Preoperative lymphoscintigraphy predicts the successful identification but is not necessary in sentinel lymph nodes biopsy in breast cancer.

BACKGROUND: Although preoperative lymphoscintigraphy in sentinel lymph node biopsy (SLNB) for breast cancer patients is undergone commonly, its clinical significance remains controversial. METHODS: We retrospectively analyzed our database that contained 636 consecutive breast cancer patients who received preoperative lymphoscintigraphy before SLNB. RESULTS: The sentinel lymph nodes (SLNs) of 86.5% of patients were well imaged by lymphoscintigraphy, and SLN were located extra-axilla in 5.3% patients. The visualization of SLN in lymphoscintigraphy was not associated with histopathologic type, location, and stage of primary tumor, as well as the time interval from injection of radiocolloid to surgery. The negative lymphoscintigraphy results were associated with excision ;biopsy before injection of radiocolloid and positive axillary node statues. The SLN was successfully detected in 625 (98.3%) enrolled patients. Failure of surgical identification of axillary SLN was associated with whether hot spot was imaged by lymphoscintigraphy. However, we identified axillary SLN in 90 (90.9%) out of 99 patients with negative axillary findings in lymphoscintigram. The false negative rate of SLNB in our study was 16.0% (15 of 94) among patients of training group, and there was no significant difference in the false negative rate between patients who had axillary hot spot in lymphoscintigram and those who had not (P = .273). CONCLUSIONS: Visualization of SLN in preoperative lymphoscintigraphy predicted the successful SLN identification. However, it was less informative for the location of SLN during operation. Considering the complexity, time consumed, and cost, lymphoscintigraphy should at present be undergone for investigation purposes only.

Colon-specific delivery tablets of sodium 4-aminosalicylic acid.

AIM: To prepare a new oral colon-specific delivery formulation and to investigate the release profile in vitro and the colon-specific delivery property in vivo in dogs. METHODS: Sodium 4-aminosalicylic acid was selected as the model drug. The combination of Eudragit RL30D and RS30D were used as sustained-release film, and Eudragit FS30D used as enteric film, which was expected to release drug depending on pH and time. The release profile of tablets was studied in three phosphate buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak for 2 h in 0.1 mol x L(-1) HCl. The tablets were radiolabelled with 99mTc to make their release times and positions in the gastrointestinal tract be followed using a gamma camera. RESULTS: For the in vitro study, there was no drug released in 0.1 mol x L(-1) HCl for 2 h, and release occurred slowly when pH was above 6.5. Drug was released faster while pH was higher. For the in vivo study, the coated tablets remained intact in the upper gastrointestinal tract, and drug release began after the colonic arrival. The uncoated tablets, however, disintegrated in the stomach of the dogs rapidly. CONCLUSION: The coating could protect the drug until the tablets reached the ascending colon, where drug was released slowly for over 10 h.