Usefulness of triple-phase thallium-201 SPECT in non-small-cell lung cancer (NSCLC): association with proliferative activity.

OBJECTIVE: The conventional delayed scan in dual phase of thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) is useful for estimating the viability of non-small-cell lung cancer (NSCLC). However, the influence of tumor blood flow cannot be ignored by the scan at 4 h after the tracer injection. For the purpose of improving the diagnostic capability and for clarifying the association between (201)Tl uptake and proliferative activity, we investigated the usefulness of super-delayed scan obtained at 24 h in triple-phase (201)Tl SPECT. METHODS: A total of 122 patients with lung nodule, 106 of NSCLC and 16 of benign nodule, were given (201)Tl SPECT before the tumor resection. Early image (15 min), delayed image (4 h), and super-delayed image (24 h) were obtained after intravenous injection of (201)Tl chloride (111 MBq). On the each SPECT image, regions of interest (ROIs) were placed over the tumor contour (T) and contra-lateral normal lung tissue (N) area on one transverse view clearly defined lesions, and T/N ratio on the early image (ER), the delayed image (DR), and the super-delayed image (sDR), and retention indexes (RI and sRI) were calculated. All patients underwent subsequent surgical excision, and the specimens were immunostained for Ki-67 and CD34. The proliferative capability was measured as a percentage of positive nuclear area for Ki-67 (MIB-1 index). The angiogenesis was measured density of positive micro-vessels for CD34 (micro-vessel density, MVD). Correlation analysis was performed to evaluate the relationship between the MIB-1 index, MVD, and SPECT parameters. RESULTS: The diagnostic accuracy of sDR in the differential of NSCLC was higher than that of DR (83.6% vs. 91.8%). Both DR and sDR were positively correlated with MIB-1 index. The correlation coefficient was higher in sDR (0.53 vs. 0.69). The MIB-1 index of the increasing pattern (RI < sRI) group was significantly higher (P < 0.001) than that of the decreasing pattern (RI > sRI) group. CONCLUSIONS: The super-delayed scan in the triple-phase (201)Tl SPECT is more useful than conventional delayed scan for both the diagnostic capability and assessing proliferation of NSCLC.

Relationship between cancer cell proliferation, tumour angiogenesis and 201Tl uptake in non-small cell lung cancer.

PURPOSE: To investigate whether 201Tl uptake is associated with cell proliferation and angiogenesis in non-small-cell lung carcinoma (NSCLC). METHODS: Eighty-four patients with scheduled NSCLC underwent 201Tl single photon emission computed tomography (SPECT) imaging: 15 min (early scan) and 240 min (delayed scan) after intravenous injection of 111 MBq of 201Tl chloride. 201Tl indices were calculated on early images (early ratio: ER) and delayed images (delayed ratio: DR). The retention index (RI) was also calculated from these two parameters. Using surgically resected cancer specimens (54 adenocarcinoma, 24 squamous cell carcinoma (SCC), six large-cell carcinoma), immunohistochemical stains for both Ki-67 (MIB-1 index) and CD34 were performed to examine the proliferative activity and the micro-vessel density (MVD), respectively. RESULTS: The mean value of 201Tl index was 1.69+/-0.77 (ER) and 2.31+/-1.08 (DR). The average RI was 42.6+/-42.9%, respectively. Both DR and RI positively correlated with MIB-1 index (r = 0.68, P < 0.05 and r = 0.52, P < 0.05). When we analyse adenocarcinoma and SCC separately, there was a significant positive correlation (r = 0.62, P < 0.05) between RI and MIB-1 index in adenocarcinoma but not in SCC (r = 0.20, P = NS). The value of ER positively correlated with MVD (r = 0.75, P < 0.05). It demonstrated strong positive correlation with both histological types (adenocarcinoma: r = 0.80, P < 0.05, SCC: r = 0.66, P < 0.05). CONCLUSION: 201Tl SPECT imaging is effective non-invasive method for assessing both the proliferation and the angiogenesis in NSCLC. Both DR and RI are useful indicators for assessing cancer cell proliferation in lung adenocarcinoma. ER is a useful marker for assessing the tumour angiogenesis in NSCLC.

[Usefulness of 201Tl SPECT in the predication of mediastinal lymph nodes metastasis in patients with non small cell lung carcinoma (NSCLC)].

Predictivity of mediastinal lymph nodes metastasis of 201Tl SPECT were examined before operation in 113 patients with non-small cell lung cancer (69 adenocarcinoma, 31 squamous cell carcinoma, 10 large cell carcinoma, 2 bronchiolo-alveolar carcinoma, 1 neuroendocrine cell carcinoma). Patients were classified into two groups, with or without lymph nodes metastasis according to the pathological diagnosis. We calculated parameters of 201Tl SPECT early ratio, delayed ratio, retention index (RI) and maximal diameters. In addition, we calculated optimal cut-off value of RI to estimate the mediastinal lymph nodes metastasis. Mediastinal lymph nodes metastasis was confirmed pathologically in 62 patients. ER and DR did not show any statistical significance between two groups. Maximal diameters of primary tumor were also comparable between two groups. RI was significantly higher in mediastinal lymph node metastasis positive group compared to that in mediastinal lymph node metastasis negative group. The sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) of 201Tl SPECT were 82.2%, 82.3%, 85.0%, 79.2% and 82.3%. These parameters were similar of higher than 72.6%, 82.4%, 83.3%, 71.2% and 77.0% of chest CT. The RI of 201Tl SPECT was useful tool for predicting lymph nodes metastasis in non-small cell lung cancer. The optimum cut-off value of RI in the prediction of mediastinal lymph nodes metastasis was 35%. We should take into account of upstaging in cases with higher RI (>35%).