Uptake of liposome-encapsulated 99Tcm-MIBI by sensitive and multidrug-resistant tumour cell lines

It is well established that accumulation of Tc-99(m)-sestamibi (Tc-99(m)-MIBI) is much higher in sensitive than multidrug-resistant tumour cells expressing the permeability glycoprotein 170 (Pgp 170) as well as a multidrug-resistance related protein (MRP). Thus Tc-99(m)-MIBI is a good candidate for diagnosing the multidrug-resistance phenotype by in vivo imaging. However, the blood clearance of Tc-99(m)-MIBI is too rapid to achieve optimal accumulation in tumours and uptake in the liver, spleen, heart and muscle is too high for it to be an excellent in vivo tumour tracer. One way of prolonging the bioavailability of Tc-99(m)- MIBI is to use liposomes which do not affect its accumulation in tumour cells. We explored this possibility in vitro using two sensitive and five resistant cell lines, two of them expressing Pgp 170 and three others over-expressing MRP. Tc-99(m)-MIBI was incorporated into liposomes prepared by thin film hydration with phosphate-buffered saline using distearoyl phosphatidyl choline, distearoyl phosphatidyl ethanolamine and cholesterol in a ratio of 1.85:0.15:1.00. Liposome diameter was 97.9 +/- 4.5 nm as determined by dynamic light scattering. Tc-99(m)-MIBI uptake was quantified by measuring radioactivity retained in the cells incubated at 37 degrees C with liposome-encapsulated Tc-99(m)-MIBI or with free radiotracer in the presence of empty liposomes. In both experimental cases, Tc-99(m)-MIBI accumulation was similar to that obtained in the presence of free Tc-99(m)-MIBI only: it was much higher in sensitive than in resistant Pgp 170-positive and MRP-positive cells. Encapsulation in liposomes does not alter the potency of Tc-99(m)-MIBI to distinguish the sensitive and resistant tumour cells. Our results suggest that future studies should assess the usefulness of the encapsulated form of Tc-90(m)-MIBI for in vivo imaging of tumours. ((C) 1999 Lippincott Williams & Wilkins).