Mechanism of 201Tl uptake in tumours

Abstract

We have studied the mechanism of tumour uptake of 201Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n = 26), lung cancer (n = 56) and lymphoma (n = 15), the time course of tumour uptake of 201Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, 99mTc labelled microspheres and 201Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for 201Tl were one tenth of those for 99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with 201Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of 201Tl compared to the cells not so exposed (0.6% +/- 0.1% vs 11.8 +/- 0.7.2% of the administered dose). The mechanism of 201Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. 201Tl uptake may provide a useful means of studying tumour viability.

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

“…In rats, the 201T1 accumulation revealed in inflammatory lesions decreased with time, but 201TI washout from malignant tumours tended to be delayed (Ando et al, 1987). In 201TI scintigraphy, the early ratio in a tumour reflects vascularity (Taguchi 1992) and blood pooling (Caluser et al, 1992), whereas the delayed ratio reflects the cell's ability to increase TIINa,K-ATP levels (Ando et al, 1988;Caluser et al, 1992;Takekawa et al, 1996) as well as the viability of tumour cells (Mountz, et al 1989;Sehweil et al, 1989). The retention index was defined thus: retention index = (delayed ratio -early ratio)/early ratio.…”

“…In an in vitro study, influx of thallium into malignant cells is regulated by its active transportation by Na,K-ATPase (Muranaka, 1981; Kishida, 1987;Sehweil et al, 1989). Since we showed that the Na,K-ATPase inhibitor ouabain blocks intracellular thallium uptake in the PC-6 cell line, Na,K-ATPase must play a vital role in intracellular thallium uptake.…”

“…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).…”

Comparison of Gadolinium-Enhanced MR and Thallium-201 Single Photon Emission Computed Tomography in Pediatric Brain Tumors

“…Even with the use of contrast agents, radiation necrosis may be indistinguishable from residual or recurrent tu mor on MR and CT [7], Although hypermetabolic tumor may be distinguishable from radiation necrosis on PET scanning, PET is expensive, not widely available, and has not been used to any extent in pediatric brain tumors [1,3], Tl-SPECT has been used in adults to differentiate high-grade gliomas from radiation necrosis [1,3]. Thal lium is a potassium analog which is transported into cells by a Na-K-ATPase-dependent pump and other cotrans port systems [1,7], Thallium uptake depends on cell membrane permeability, tumor type, regional blood How, and blood-brain barrier permeability and is not affected by steroid administration [3], Intense thallium uptake by neoplastic cells depends on active tumor metabolism.…”

“…Thal lium is a potassium analog which is transported into cells by a Na-K-ATPase-dependent pump and other cotrans port systems [1,7], Thallium uptake depends on cell membrane permeability, tumor type, regional blood How, and blood-brain barrier permeability and is not affected by steroid administration [3], Intense thallium uptake by neoplastic cells depends on active tumor metabolism. Regions of moderate thallium uptake may represent reac tive changes due to radiation damage without the pres ence of active tumor, cerebral candidiasis, bacterial ab scesses, hematomas, and infarcts [1,3,[8][9][10], In the set ting of malignant supratentorial gliomas, a thallium index <1.5 almost excludes the probability that the lesion is malignant [1].…”