Predicting chemotherapeutic response to small-cell lung cancer of platinum compounds by thallium-201 single-photon emission computerized tomography

Abstract

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...

Intracellular accumulation of thallium as a marker of cisplatin cytotoxicity in nonsmall cell lung carcinoma

“…Our present and past11 results suggest that intracellular accumulation of Tl could be a suitable marker of CDDP cytotoxity. On the other hand, no significant correlation was observed between the cellular accumulation of CDDP and Tl.…”

“…From these findings, we speculated that a lung tumor that has a high degree of 201 Tl uptake may also accumulate a high degree of CDDP and, therefore, may have a high CDDP sensitivity. In fact, in our previous study on small cell lung carcinoma (SCLC) patients who had undergone 201 Tl SPECT, we found that 201 Tl accumulation correlated to patient response to chemotherapy of platinum compounds 11. Based on this clinical study, we hypothesized that a significant correlation exists between the in vitro accumulations of CDDP and Tl.…”

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

“…Tumor retention of Thallium-201 (T201) on SPECT scanning may reflect Na+, K+ ATPase activity, and in one study in which SCLC patients were treated with cisplatin-based chemotherapy, response correlated with pretreatment T201 retention112, but this was not noted in another study in which SCLC patients were treated with a broader spectrum of chemotherapy agents113, and no correlation between T201 retention and outcome was seen in NSCLC patients treated with mitomycin-vindesine-cisplatin114. Hence, it is unclear if T201 scanning is of any value in this setting.…”

Scintigraphic prediction of resistance to radiation and chemotherapy in patients with lung carcinoma

“…18,19 Therefore, it may be expected that 201 Tl would be useful in predicting the therapeutic response and prognosis of patients with this type of tumor. 20,21 In the current study, we evaluated whether a therapeutic response in patients with lung carcinoma is predictable by dual-isotope single photon emission computed tomography (SPECT) with 99m Tc-TF and 201 Tl. We employed a dual-isotope SPECT, which is well established in the field of nuclear medicine.…”