Scleroderma presenting with multiple keloids.

Abstract

<b>236</b> <h3><b>Objectives</b></h3> Triazacyclononane-phosphinate chelators (TRAP) allow for ⁶⁸Ga-labeling with high specific activity. To transfer the excellent labeling characteristics of TRAP to monomeric ligands, we developed the monoconjugable chelator NOPO. We report on the ⁶⁸Ga labeling properties and the preclinical characterization of the first two NOPO conjugates with peptidic receptor ligands. <h3><b>Methods</b></h3> Fully characterized NOPO was labeled with ⁶⁸Ga using non-purified eluate of an SnO₂-based ⁶⁸Ge/⁶⁸Ga generator. Selectivity for ⁶⁸Ga was investigated in the presence of various metal chlorides. Conjugates with c(RGDfK) (NOPO-RGD) and NaI-octreotide (NOPO-NOC) were prepared using standard peptide coupling methods. Automated production of ⁶⁸Ga-NOPO-RGD and ⁶⁸Ga-NOPO-NOC was performed on SCINTOMICS Gallelut⁺ system. Biodistribution studies and preclinical PET imaging with ⁶⁸Ga-NOPO-RGD and ⁶⁸Ga-NOPO-NOC were done using nude mice with M21/M21L and AR42J xenografts, respectively. <h3><b>Results</b></h3> ⁶⁸Ga labeling of NOPO conjugates proceeds rapidly and efficiently at r.t. NOPO possesses high selectivity for ⁶⁸Ga in the presence of high concentrations of Zn²⁺, Cu²⁺, Fe³⁺, Al³⁺, Ti⁴⁺, and Sn⁴⁺. No incorporation of ⁶⁸Ge was observed. ⁶⁸Ga-NOPO-RGD was prepared with specific activities &gt; 5000 GBq/µmol. No loss of ⁶⁸Ga was observed upon competition with 0.25 M EDTA, in PBS at 37 °C, and in vivo. M21 tumor uptake of ⁶⁸Ga-NOPO-RGD was comparable to that of ⁶⁸Ga-NODAGA-RGD and ¹⁸F-Galacto-RGD. Furthermore, due to the high polarity of NOPO, the conjugate exhibited very high hydrophilicity (logP = -4.6), resulting in fast renal excretion. Similarly, ⁶⁸Ga-NOPO-NOC was stable in vivo, showed high tumor uptake with low background, and excretion via kidneys. <h3><b>Conclusions</b></h3> NOPO keeps the unique labeling properties of symmetrical TRAP chelators while allowing for straightforward monoconjugation. Its ⁶⁸Ga-labeled conjugates are fully stable and possess favorable in vivo properties. Therefore, NOPO perfectly enhances the portfolio of chelators for synthesis of ⁶⁸Ga radiopharmaceuticals