Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

Evaluation of Simultaneous Dual-radioisotope SPECT Imaging Using (18)F-fluorodeoxyglucose and (99m)Tc-tetrofosmin.

OBJECTIVES: Use of a positron emission tomography (PET)/single-photon emission computed tomography (SPECT) system facilitates the simultaneous acquisition of images with fluorine-18 fluorodeoxyglucose ((18)F-FDG) and technetium ((99m)Tc)-tetrofosmin. However, (18)F has a short half-life, and 511 keV Compton-scattered photons are detected in the (99m)Tc energy window. Therefore, in this study, we aimed to investigate the consequences of these facts. METHODS: The crosstalk correction for images in the (99m)Tc energy window involved the dual energy window (DEW) subtraction method. In phantom studies, changes in the count of uniform parts in a phantom (due to attenuation from decay), signal detectability in the hot-rod part of the phantom, and the defect contrast ratio in a cardiac phantom were examined. RESULTS: For (18)F-FDG in the step-and-shoot mode, nearly a 9% difference was observed in the count of projection data between the start and end positions of acquisition in the uniform part of the phantom. Based on the findings, the detectability of 12 mm hot rods was relatively poor. In the continuous acquisition mode, the count difference was corrected, and detectability of the hot rods was improved. The crosstalk from (18)F to the (99m)Tc energy window was approximately 13%. In the cardiac phantom, the defect contrast in (99m)Tc images from simultaneous dual-radionuclide acquisition was improved by approximately 9% after DEW correction; the contrast after correction was similar to acquisition with (99m)Tc alone. CONCLUSION: Based on the findings, the continuous mode is useful for (18)F-FDG acquisition, and DEW crosstalk correction is necessary for (99m)Tc-tetrofosmin imaging.