Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system

Abstract

Imaging recognition of multidrug-resistance by 99mTc-labeled sestamibi, tetrofosmin and furifosmin in mice bearing human breast tumors was evaluated using a high-resolution SPECT, FASTSPECT. Imaging results showed that the washout rates in drug-resistant MCF7/D40 tumors were significantly greater than that in drug-sensitive MCF7/S tumors. Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only. Feasibility of the monocationic agents for characterizing MDR expression was well clarified with FASTSPECT imaging.

Fig. 1

Expression of Pgp in MCF7/S and MCF7/D40 human breast tumors from 3 representative mice in each group (^99mTc-sestamibi, ^99mTc-tetrofosmin and ^99mTc-furifosmin), as determined by Western blots of plasma membrane preparations with mAb C219. The arrow identifies Pgp at 170kDa.

Fig. 2

Three-dimensional representation (A) of a reconstructed FASTSPECT data set of the right thigh with subcutaneous MCF7/S tumor (arrow) in a mouse (B) 10-min after injection with ^99mTc-tetrofosmin. C & D are two selected coronal slices. The tumor (arrow) was visualized on slice D.

Fig. 3

Representative FASTSPECT dynamic images (selected coronal slices) from two mice with MCF7/S breast tumor (A) and MCF7/D40 tumor (B) using ^99mTc-sestamibi. The time after injection is shown in the lower right corner of each image. The MCF7/S tumor (arrow) was visualized about 2 min post-injection and stayed well-defined for at least 30 min. The MCF7/D40 tumor (arrow) was visible for only about 2–3 min post-injection. The tumor weight was 0.084 g (MCF7/S) and 0.15 g (MCF7/D40). The ratio of tumor/muscle was 1.45 (MCF7/S) and 0.72 (MCF7/D40) determined by biodistribution analysis at the end of imaging session.

Fig. 4

Dynamic images from two mice with MCF7/S breast tumor (A) and MCF7/D40 tumor (B) using ^99mTc-tetrofosmin (transaxial slices). The MCF7/S tumor (arrow) was visible clearly from 2 min to 30 min consistently. The MCF7/D40 tumor (arrow) was well identified at 2 min post-injection. After 3 min, the radioactivity in the tumor quickly dropped to the background level. The tumor weight was 0.09 g (MCF7/S) and 0.04 g (MCF7/D40). The ratio of tumor/muscle was 1.31 (MCF7/S) and 0.59 (MCF7/D40), respectively.

Fig. 5

^99mTc-furifosmin dynamic images (sagittal slices) from two mice with MCF7/S breast tumor (A) and MCF7/D40 tumor (B). The MCF7/S tumor (arrow) became visible 2–5 min and remained detectable until 30 min post-injection. The MCF7/D40 tumor (arrow) was visualized 2–5 min post-injection. The tumor weight was 0.11 g (MCF7/S) and 0.07 g (MCF7/D40). The ratio of tumor/muscle was 0.93 (MCF7/S) and 0.41 (MCF7/D40), respectively.

Fig. 6

^99mTc-sestamibi (MIBI), ^99mTc-tetrofosmin (TF) and ^99mTc-furifosmin (Q12) clearance curves from MCF7/S and MCF7/D40 breast tumors. The radioactivity is plotted as percent of the peak activity in the tumor. S = MCF7/S; D40 = MCF7/D40.

Fig. 7

^99mTc-sestamibi, ^99mTc-tetrofosmin and ^99mTc-furifosmin fractional washout (%) from MCF7/S and MCF7/D40 tumors. * p<0.05 compared to ^99mTc-sestamibi; + p<0.05 compared to ^99mTc-tetrofosmin.