Summary Thallium-201 single-photon emission computerized tomography (SPECT) was used to clarify the relationship between 201TI uptake and the response in chemotherapy to platinum compounds in 21 patients with small-cell lung cancer. 201TI-SPECT scans were obtained twice: at 15 min (early scan) and 120 min (delayed scan) after an intravenous injection of 111 MBq (3 mCi) of thallium-201 chloride. We obtained the uptake ratio from each scan and calculated the retention index:uptake ratio = region of interest uptake / contralateral normal lung uptake; retention index = (delayed ratio -early ratio)/early ratio. After 201TI scintigraphy, 12 patients received chemotherapy consisting of platinum compounds and nine were treated with chemoradiation. Among patients receiving only chemotherapy, the retention index correlated with the responses to chemotherapy. In an in vitro study, ouabain, an inhibitor of the Na,K-ATPase pump, reduced sensitivity to cisplatin and inhibited intracellular thallium uptake in the small-cell lung cancer cell line. These studies suggest that 201TI-SPECT is a useful indicator of response to chemotherapy with platinum compounds in small-cell lung cancer, and that Na,K-ATPase is commonly involved in transporting both thallium and platinum compounds into cancer cells.Keywords: 201TI-SPECT; chemotherapy; inductively coupled plasma mass spectrometry; cisplatin; Na,K-ATPase Cisplatin (CDDP) is a useful anti-cancer agent, particularly when used in the treatment of human ovarian, testicular, bladder and small-cell lung cancer (Loehrer et al, 1984;Ohmori et al, 1993). Many studies on cisplatin resistance mechanisms have revealed that the decline in intracellular accumulation of cisplatin is important in carcinoma cell lines (Hromas et al, 1987;Kraker and Moore, 1988;Andrews and Howell, 1990;Mann et al, 1990). Cisplatin accumulation in these cells is reported to be regulated by an alteration in their Na,K-ATPase levels (Kawai et al, 1987;Andrews et al, 1991;Ohmori et al, 1993). Thus, the response to chemotherapy with cisplatin might depend on alterations of Na,K-ATPase.Thallium-201 (201TI) scintigraphy is now used to diagnose myocardial infarction (Strauss et al, 1975), myocardial ischaemia (Strauss and Boucher, 1986) and thyroid tumour (Bleichrodt et al, 1987;Charkes et al, 1990). Recently, 207T1 single-photon emission computerized tomography (SPECT) was reported as being used to detect lung lesion (Tonami et al, 1989), and it is reportedly superior to gallium scintigraphy in detecting lung cancer (Itoh et al, 1992;Matsuno et al, 1992). Some studies demonstrated that TI accumulation in 201T1 scintigraphy is closely related to the Na,K-ATPase levels in malignant tumours (Britten and Blank, 1968;Muranaka, 1981;Kishida, 1987;Sehweil et al, 1989). And we reported that the delayed ratio is related to low levels of Na,K-ATPase activity (Takekawa et al, 1996). We hypothesized that the degree of TI uptake to tumour in 201Tl scintigraphy is associated with the response to chemotherapy with platinum compounds th...

Wereport a case of mucousgland adenomaof the trachea in a 73-year-old male revealed by bronchoscopy. The tumor was resected with a contact neodymium:yttrium aluminum garnet (Nd-YAG)laser after five years of observation. The tumor was histologically peculiar because it presented numerous cystically dilated, or irregularly shaped mucus-filled glands lined with cuboidal or tall columnar cells. In some parts, the lining cells of the tumor showed papillary proliferation. Wediagnosed this tumor as a mucous gland adenomaof the trachea. Wereview the clinical features of this rare tumor and discuss the usefulness of the laser in the diagnosis and the therapy. (Internal Medicine 35: 890-893, 1996)

Background: Inductively coupled plasma mass spectrometry (ICP-MS) has been used to detect trace elements in biologic materials. In this study, we evaluated its application for the determination of cisplatin (cis-diamminedichloroplatinum) accumulation in human non-small cell lung cancer cell lines. Methods:We used 2 squamous lung cancer cell lines (EBC-1 and LK-2), and 4 adenocarcinoma cell lines (ABC-1, RERF-LC-MS, A549, and its cisplatin-resistant subline A549/CDDP). The cells were incubated in 10 ppb cisplatin for 2 hours. After the incubation, cells were digested with nitric acid at 120~ diluted with filtered water, and nebulized into an ICP-MS machine. A calibration curve was obtained using 5 standard platinum solutions, and cellular platinum concentrations were corrected by protein. Chemosensitivity to cisplatin was determined using the XTT assay. Results: The cell-number detection limit for the determination of cellular platinum was 5.0 x 104 cells for 10 ppb cisplatin. No significant correlation was observed between cisplatin sensitivity and cellular platinum accumulation among these 6 cell lines, but an inverse correlation was observed between A549/ CDDP and its parental line. Conclusion: This study indicates that ICP-MS can be applied to the determination of platinum accumulation in human non-small cell lung cancer cell lines.Int J Clin Oncol 1998;3:98-101

BACKGROUND Thallium‐201 (201Tl) scintigraphy has been used to detect malignant pulmonary disease. The mechanism of Tl influx in tumor cells is believed to be similar to that of cisplatin (CDDP) mediated by sodium‐ and potassium‐activated adenosine triphosphatase (Na‐K ATPase), and the Na‐K ATPase activity may determine the cellular CDDP accumulation and sensitivity to CDDP. The objective of this study was to determine the accumulation of CDDP and Tl in vitro by using inductively coupled plasma mass spectrometry (ICP‐MS), a new analytic technique for detecting ultra trace elements, and to evaluate the correlations between cellular CDDP and Tl accumulation, between CDDP 50% inhibitory concentration (IC50) values and cellular CDDP accumulation, and between CDDP IC50 values and cellular Tl accumulation. METHODS Eight nonsmall cell lung carcinoma (NSCLC) cell lines were used (five adenocarcinomas and three squamous cell carcinomas). The cell lines were exposed to CDDP or Tl for 1 hour, and the resulting cellular accumulation of platinum and Tl was determined by ICP‐MS. CDDP IC50 values were determined by a soluble tetrazolium/formazan assay. RESULTS The authors were able to measure cellular CDDP and Tl accumulation precisely, and heterogeneity in the cellular accumulation of CDDP and Tl existed among the NSCLC cell lines. A significant inverse correlation was observed between CDDP IC50 values and the cellular accumulation of both CDDP and Tl. CONCLUSIONS ICP‐MS is suitable for the determination of cellular CDDP and Tl accumulation in NSCLC cell lines. Cellular Tl accumulation determined by ICP‐MS may reflect CDDP cytotoxicity rather than cellular CDDP accumulation. Cancer 1998;83:930‐935. © 1998 American Cancer Society.

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