(0000-0002-4358-5171) Ludwig, F.-A., Lis, C., (0000-0001-6104-6676) Ullrich, M., Lankau, H.-J., (0000-0002-2876-9925) Sihver, W., Joseph, D., Eiselt, E., Meyer, C., (0000-0001-9743-2325) Gündel, D., (0000-0003-3168-3062) Deuther-Conrad, W., (0000-0001-5555-7058) Brust, P., Donat, C. K., (0000-0002-8029-5755) Bachmann, M., (0000-0001-5286-4319) Pietzsch, H.-J., (0000-0002-1610-1493) Pietzsch, J., Fischer, S., (0000-0003-4846-1271) Kopka, K., Hoepping, A., (0000-0002-4358-5171) Ludwig, F.-A., Lis, C., (0000-0001-6104-6676) Ullrich, M., Lankau, H.-J., (0000-0002-2876-9925) Sihver, W., Joseph, D., Eiselt, E., Meyer, C., (0000-0001-9743-2325) Gündel, D., (0000-0003-3168-3062) Deuther-Conrad, W., (0000-0001-5555-7058) Brust, P., Donat, C. K., (0000-0002-8029-5755) Bachmann, M., (0000-0001-5286-4319) Pietzsch, H.-J., (0000-0002-1610-1493) Pietzsch, J., Fischer, S., (0000-0003-4846-1271) Kopka, K., and Hoepping, A. more...
Objectives: During the last 15 years several PSMA PET ligands for prostate cancer imaging have been developed resulting in the recent approvals of 68Ga-PSMA-11, 18F-PSMA-1007 and 18F-DCFPyL.[1,2] However, 99mTc remains a popular radiometal for SPECT imaging due to its longer half-life and availability from 99Mo/99mTc generators especially in outpatient imaging centers. Due to the widespread availability of SPECT cameras PSMA SPECT ligands have the potential to substantially extend the availability of PSMA-based imaging, but currently no PSMA SPECT ligand is approved. MIP-1404, PSMA-I&S and HYNIC-iPSMA are rare examples of PSMA SPECT tracers in clinical development. Accordingly, the aim of our study was to develop a PSMA ligand for 99mTc SPECT imaging of prostate cancer based on an N2S2 chelator, which enables reliable radiolabeling to form stable 99mTc complexes.[3] Methods: A number of compounds, which contain the PSMA binding motif Glu-urea-Lys, a varying linker and a bisaminothiol (BAT)-type N2S2 chelator, were synthesized. Selected compounds were radiolabeled with 99mTc, followed by assessment of in vitro stability of the formed complexes via radio-HPLC. The specific binding affinity towards PSMA and the internalization of the radioligands were examined in LNCaP cells, supplemented by autoradiographic studies. Tissue distribution and tumor accumulation were evaluated in LNCaP-tumor bearing mice via quantitative SPECT/CT imaging, benchmarked with [99mTc]Tc-PSMA-I&S[4] and [68Ga]Ga-PSMA-11. Results: Among the six 99mTc radioligands synthesized and examined, [99mTc]TcO-ABX474 showed most favorable properties. Radiolabeling of ABX474 (50 µg) was achieved starting from [99mTc]NaTcO4 (0.2-2 GBq) in saline (1.4 mL) using SnCl2 (1 µg in 0.01 M HCl) as reducing agent, in presence of calcium-D-heptagluconate (10 µg) and D-mannitol (1 mg) at pH 5-6. Incubation at r.t. for 20 min followed by heating at 80°C for 20 min afforded the product-containing solution with a radioche more...