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Radiochemical and Biological Evaluation of 3p-<i>C</i>-NETA-ePSMA-16, a Promising PSMA-Targeting Agent for Radiotheranostics

Bifunctional chelators (BFCs) are a key element in the design of radiopharmaceuticals. By selecting a BFC that efficiently complexes diagnostic and therapeutic radionuclides, a theranostic pair possessing almost similar biodistribution and pharmacokinetic properties can be developed. We have previou...

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Main Authors: Erika Murce (Author), Stephen Ahenkorah (Author), Savanne Beekman (Author), Maryana Handula (Author), Debra Stuurman (Author), Corrina de Ridder (Author), Frederik Cleeren (Author), Yann Seimbille (Author)
Format: Book
Published: MDPI AG, 2023-06-01T00:00:00Z.
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Summary:Bifunctional chelators (BFCs) are a key element in the design of radiopharmaceuticals. By selecting a BFC that efficiently complexes diagnostic and therapeutic radionuclides, a theranostic pair possessing almost similar biodistribution and pharmacokinetic properties can be developed. We have previously reported 3p-<i>C</i>-NETA as a promising theranostic BFC, and the encouraging preclinical outcomes obtained with [<sup>18</sup>F]AlF-3p-<i>C</i>-NETA-TATE led us to conjugate this chelator to a PSMA-targeting vector for imaging and treatment of prostate cancer. In this study, we synthesized 3p-<i>C</i>-NETA-ePSMA-16 and radiolabeled it with different diagnostic (<sup>111</sup>In, <sup>18</sup>F) and therapeutic (<sup>177</sup>Lu, <sup>213</sup>Bi) radionuclides. 3p-<i>C</i>-NETA-ePSMA-16 showed high affinity to PSMA (IC<sub>50</sub> = 4.61 ± 1.33 nM), and [<sup>111</sup>In]In-3p-<i>C</i>-NETA-ePSMA-16 showed specific cell uptake (1.41 ± 0.20% ID/10<sup>6</sup> cells) in PSMA expressing LS174T cells. Specific tumor uptake of [<sup>111</sup>In]In-3p-<i>C</i>-NETA-ePSMA-16 was observed up to 4 h p.i. (1.62 ± 0.55% ID/g at 1 h p.i.; 0.89 ± 0.58% ID/g at 4 h p.i.) in LS174T tumor-bearing mice. Only a faint signal could be seen at 1 h p.i. in the SPECT/CT scans, whereas dynamic PET/CT scans performed after administration of [<sup>18</sup>F]AlF-3p-<i>C</i>-NETA-ePSMA-16 in PC3-Pip tumor xenografted mice resulted in a better tumor visualization and imaging contrast. Therapy studies with short-lived radionuclides such as <sup>213</sup>Bi could further elucidate the therapeutic potential of 3p-<i>C</i>-NETA-ePSMA-16 as a radiotheranostic.
Item Description:10.3390/ph16060882
1424-8247

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