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. 2023 Jan;7(1):75-82.
doi: 10.1109/trpms.2022.3201757. Epub 2022 Aug 26.

Simultaneous Imaging of Ga-DOTA-TATE and Lu-DOTA-TATE in Murine Models of Neuroblastoma

Yifan Zheng  1 , Yoonsuk Huh  2 , Kai Vetter  3 , Nicole Nasholm  3 , Clay Gustafson  3 , Youngho Seo  4
Affiliations

Simultaneous Imaging of Ga-DOTA-TATE and Lu-DOTA-TATE in Murine Models of Neuroblastoma

Yifan Zheng et al. IEEE Trans Radiat Plasma Med Sci. 2023 Jan.

Abstract

68Ga-DOTA-TATE and 177Lu-DOTA-TATE are radiolabeled somatostatin analogs used to detect or treat neuroendocrine tumors. They are administered separately for either diagnostic or therapeutic purposes but little experimental data for their biokinetics are measured simultaneously in the same biological model. By co-administering 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in three laboratory mice bearing two IMR32 tumor xenografts expressing different levels of somatostatin receptors (SSTRs) on their shoulders and imaging both 68Ga and 177Lu simultaneously, we investigated the relationship between the uptake of 68Ga-DOTA-TATE and 177Lu-DOTA-TATE in organs and tumors. In addition, using the percent of injected activity (%IA) values of 68Ga-DOTA-TATE at 0 hr and 4 hr, we investigated the correlation between 68Ga-DOTA-TATE %IA and the time-integrated activity coefficients (TIACs) of 177Lu-DOTA-TATE to estimate the organ-based and tumor-based doses of 177Lu-DOTA-TATE. The results showed that the extrapolated clearance time of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32-SSTR2 tumor, kidneys, brain, heart, liver, stomach and remainder body. The extrapolated %IA value at 0 hr of 68Ga-DOTA-TATE linearly correlated with the TIACs of 177Lu-DOTA-TATE in the IMR32 tumor and lungs. In our murine study, both kidneys and lungs were organs that showed high absorbed doses of 177Lu-DOTA-TATE.

Keywords: 177Lu-DOTA-TATE; 68Ga-DOTA-TATE; IMR32; SSTR; neuroblastoma; neuroendocrine tumor; radiation dosimetry; somatostatin receptor.

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Figures

Fig. 1.
Fig. 1.
The flowchart of calculating and estimating absorbed doses of 177Lu-DOTA-TATE.
Fig. 2.
Fig. 2.
(a) A coronal slice of the reconstructed CT image, SPECT image of 68Ga-DOTA-TATE (shown in green colormap) and SPECT image of 177Lu-DOTA-TATE (shown in hot iron colormap) of Mouse 1 at 4 hr postinjection. Each voxel is 0.08 mm × 0.08 mm × 0.08 mm. (b) The segmentation of (a).
Fig. 3.
Fig. 3.
The %IA values of 177Lu-DOTA-TATE in the segmented source organs and the %IA values of excretion at the five measurement time points. We fitted the segmented source organs with the biexponential function (and the exponential decay function for the heart of Mouse 3) and fitted excretion with the inverse-exponential function to obtain a˜, the TIACs of 177Lu-DOTA-TATE.
Fig. 4.
Fig. 4.
The %IA values of 68Ga-DOTA-TATE in the segmented source organs and the total body at the two measurement time points.
Fig. 5.
Fig. 5.
Fitting from the quantities of the %IA values of 68Ga-DOTA-TATE to the TIACs of 177Lu-DOTA-TATE in the source organs of the three mice. The extrapolated clearance time tc gave the best fitting in tumor2l, kidneys, brain, stomach, heart, liver and the remainder body. The extrapolated %IA value at 0 hr %IA(0) gives the best fitting in tumor1r and lungs. The errors of the TIACs of 177Lu-DOTA-TATE came from the errors of the fitting parameter when calculating the TIACs in Figure 3.
Fig. 6.
Fig. 6.
The absorbed doses of 177Lu-DOTA-TATE in the target organs in the three mice. The x-axis is the referenced dose calculated using the measurement of 177Lu-DOTA-TATE, and the y-axis shows the estimated dose calculated using the measurement of 68Ga-DOTA-TATE. The unit of the absorbed dose is mGy per MBq of injected 177Lu-DOTA-TATE.
See this image and copyright information in PMC

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