technetium-tc-99m-depreotide and Carcinoma--Non-Small-Cell-Lung

Several tumors overexpress somatostatin receptors (SSTR) and can thus be imaged with radiolabeled analogues of somatostatin. Tc-99m depreotide is a new radiolabeled somatostatin analogue that shows high affinity for SSTR2, SSTR3, and SSTR5 subtypes. It has been recently FDA-approved for use in the evaluation of indeterminate solitary pulmonary nodules. SPECT with Tc-99m depreotide is highly accurate in this clinical setting and may be preferable to FDG-PET because of its lower cost and wider availability. Large studies are also underway to evaluate the accuracy of Tc-99m depreotide in staging of lung cancer.

Topics: Carcinoma, Non-Small-Cell Lung; Fluorodeoxyglucose F18; Humans; Lung; Lung Neoplasms; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Solitary Pulmonary Nodule; Somatostatin

To investigate the potential role of Tc-99m depreotide (Tc-DEPR) in the preoperative lymph node (N) staging of non-small-cell lung cancer (NSCLC).. Sixty-one patients with NSCLC at the potentially operable stage were enrolled and underwent scintigraphy before surgery (n=56) or mediastinoscopy (n=5). Imaging was performed with a hybrid single photon emission computed tomography/computed tomography (SPECT/CT) system. Depreotide uptake in N stations was evaluated visually and semi-quantitatively and compared to histology. Quantification was carried out in attenuation-corrected SPECT slices. Different sites of normal uptake were used as a reference for comparison with lesional uptake. Receiver operating characteristic analysis was employed to identify the most preferable reference area and the cut-off best discriminating disease-free from disease-involved lymph nodes.. With reference to 53 Ν1 hilar and 147 Ν2/Ν3 sampled stations, sensitivity of scintigraphy by visual interpretation was 100 and 94%, specificity 43 and 59% and accuracy 55 and 67%, respectively. No patient was down-staged, but 52% were incorrectly up-staged and 44% were misclassified as inoperable. Compared to scintigraphy, preoperative contrast-enhanced diagnostic CT demonstrated lower sensitivity (36% for hilar and 73% for N2/N3 stations), higher specificity (79 and 75%) and similar accuracy (70 and 75%). Regarding the ultimate N-stage and the prediction of surgical disease, diagnostic CT was wrong in 51 and 34% of cases. Dichotomy of quantitative scintigraphic data by the use of certain N-to-spine ratio cut-offs resulted in a significant increase of specificity (76% for hilar and 89% for N2/N3 stations), while sensitivity remained high (82% in both circumstances) and accuracy for Ν2/Ν3 stations was substantially improved (88%). By this quantitative approach, misclassifications as to the N-stage and patient operability (25 and 16%) were considerably less than that of visual Tc-DEPR and diagnostic CT interpretations.. Tc-99m depreotide SPECT/CT seems to have a role in the N-staging of NSCLC, mainly because of its high sensitivity and negative predictive value. Quantification of uptake can improve specificity, at a low cost of sensitivity. If F-18 fluoro-deoxyglucose positron emission tomography is not available, this method may be used as a surrogate to conventional staging modalities.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Humans; Image Processing, Computer-Assisted; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Multimodal Imaging; Neoplasm Staging; Organotechnetium Compounds; Preoperative Period; Somatostatin; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

The (99m)Tc-labeled agent, ((99m)TcO)depreotide, has received regulatory approval in the United States and Europe for use in the detection of cancer. It is essential to establish a simple and reliable method of direct radiolabeling of (99m)Tc-depreotide and to investigate its specific receptor binding properties with human non small cell lung cancer (NSCLC) A549 cell in vitro. So we made some researches as follow: Depreotide was labeled with (99m)Tc using SnCl2 as a reductant. Labeling efficiencies at different pH values and temperatures were compared. Radioreceptor assay was used to observe the uptake kinetics, stagnation and retention half time of (99m)Tc-depreotide in A549 cells. As the results of the investigation ,many facts is shown below: The labeling rate of pH 6.0 group was higher than that of pH 5.0 and pH7.0 groups. The labeling rate decreased when temperature increased from 15 °C to 50 °C. The uptake rate increased with rising temperature, and the maximum uptake was observed at 60 min at 37 °C. The cleaning curves were similar at different temperatures, and the half cleaning time at 37 °C was 48 min. The results showed that the optimal conditions for labeling depreotide with (99m)Tc was found to be below 15 °C at a pH lower than 6.0. Furthermore, at 37 °C, (99m)Tc-depreotid may have the potential as an ideal imaging agent for somatostatin receptors.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Stability; Humans; Hydrogen-Ion Concentration; Lung Neoplasms; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Temperature

Somatostatin receptor (SSTR) scintigraphy with (99m)Tc-depreotide is used for differential diagnosis of solitary pulmonary nodules. The method is based on SSTR expression in cancer tissue.. To estimate the expression of SSTRs in non-small-cell lung cancer (NSCLC) in vitro, and to determine the correlation between (99m)Tc-depreotide uptake in vivo and different tumor characteristics determined in vitro, such as tumor grade, and presence of SSTR2, MIB-1, and p53.. A total of 127 patients with lung lesions detected on computed tomography (CT) were investigated with SSTR scintigraphy after injection of 740 MBq (99m)Tc-depreotide. This study includes 19 patients with NSCLC with histologically proven diagnosis. The quantitative evaluation of (99m)Tc-depreotide was performed using region-of-interest analysis and includes tumor counts/cm(3), background counts/cm(3), and the ratio between tumor and background counts.. 99mTc-depreotide uptake was found in all NSCLC tumors, which expressed SSTR2 defined in vitro by immunochemical methods. SSTR2 expression was negatively correlated to the degree of the tumor's differentiation (P<0.05). 99mTc-depreotide uptake in tumor cells did not correlate with tumor grade, or SSTR2, MIB-1, or p53 expression.. There is an expression of SSTRs in NSCLC. The degree of tumor differentiation correlates negatively with SSTR2 measured in vitro and positively with MIB-1 expression in tumor tissue. No correlation was found between (99m)Tc-depreotide uptake and possible prognostic factors such as MIB-1 and p53 expression in tumor cells in NSCLC. Lastly, no correlation was found between (99m)Tc-depreotide uptake and tumor grade or SSTR2 expression.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin

The affinity of various malignant neoplasms including small cell and non-small cell lung cancer for peptide analogs of somatostatin has been well documented. Depreotide is such an analog and can be complexed with technetium-99m ((99m)Tc depreotide) for optimal imaging properties. Using this radiopharmaceutical, solitary pulmonary nodules (SPN) were previously evaluated in a successful phase II/III trial. The results of the larger multicenter phase III study using (99m)Tc depreotide to differentiate malignant and benign etiologies in SPN are now presented.. Patients with SPN 30 years, and no demonstrable radiographic stability for the prior 2 years were studied. All underwent single-photon emission CT (SPECT) with (99m)Tc depreotide and subsequent tissue histologic examination. Three nuclear medicine specialists blinded to histologic findings examined the SPECT images and scored them as positive or negative based on the presence or absence of activity in the radiographic region of the SPN. The final result was determined by the majority score, which was then compared with the histologic result.. Of the 114 individuals studied, 88 had a histologic result compatible with malignant neoplasm. (99m)Tc depreotide scintigraphy correctly identified 85 of this group, with three false-negative determinations compared with histology. There were seven false-positive determinations, including six granulomas and one hamartoma. (99m)Tc depreotide scintigraphy correctly excluded malignancy in 19 of 26 patients with benign histologic findings. The sensitivity of this method was 96.6% with a specificity of 73.1%.. (99m)Tc depreotide scintigraphy is a safe and useful method for the noninvasive evaluation of SPN with a sensitivity and accuracy comparable to that reported for fluorine-18 fluorodeoxyglucose positron emission tomography.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Contrast Media; Diagnosis, Differential; Female; Humans; Image Enhancement; Intercellular Signaling Peptides and Proteins; Lung; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Peptides; Predictive Value of Tests; Prospective Studies; Solitary Pulmonary Nodule; Somatostatin; Tomography, Emission-Computed, Single-Photon