Convenient Preparation of 18F-Labeled Peptide Probes for Potential Claudin-4 PET Imaging

Abstract

Since pancreatic cancer is often diagnosed in a late state of cancer development, diagnostic opportunities allowing early disease detection are highly sought after. As such, cancer expression of claudin proteins is markedly dysregulated, making it an attractive target for molecular imaging like positron emission tomography (PET). Claudins are a family of transmembrane proteins that have a pivotal role as members of the tight junctions. In particular, claudin-3 and claudin-4 are frequently overexpressed in pancreatic cancer. 18F-Labeled claudin selective peptides would provide access to a novel kind of imaging tools for pancreatic cancer. In this work we describe the synthesis of the first 18F-labeled probes potentially suitable for PET imaging of claudin-4 expression. These probes were prepared using oxime ligation of 5-[18F]fluoro-5-deoxyribose (5-[18F]FDR) to claudin selective peptides. As a proof-of-principle, one of them, 5-[18F]FDR-Clone 27, was isolated in >98% radiochemical purity and in 15% radiochemical yield (EOB) within 98 min, and with a molar activity of 4.0 GBq/μmol (for 30 MBq of tracer). Moreover, we present first biological data for the prepared 5-FDR-conjugates. These tracers could pave the way for an early diagnosis of pancreatic tumor, and thus improve the outcome of anticancer therapy.

Efficient cartridge purification for producing high molar activity [18F]fluoro-glycoconjugates via oxime formation

“…The gradient program was 0-3 min: 40% B, [3][4][5][6][7][8][9][10][11][12][13][14][15] water, and purified with HPLC. Separation was carried out on a Grace Alltima C18 column (5 μm, 250 mm × 4.6 mm) with a flow rate of 1 ml min -1 .…”

Sweetening Pharmaceutical Radiochemistry by ¹⁸F-Fluoroglycosylation: Recent Progress and Future Prospects

“…The Neumaier group synthesized and studied various 18 F-labeled peptides for imaging of claudin-4 as candidate tracers for PET imaging of pancreatic tumors [29]. The various [ 18 F]FDR-conjugated peptides 74-77 were synthesized via oxime ligation of claudinderived peptides, applying [ 18 F]FDR obtained by 18 F-labeling of the naphthalene onium salt of 5-deoxyribose (Table 1).…”

“…The various [ 18 F]FDR-conjugated peptides 74-77 were synthesized via oxime ligation of claudinderived peptides, applying [ 18 F]FDR obtained by 18 F-labeling of the naphthalene onium salt of 5-deoxyribose (Table 1). The 18 F-glycosylated peptide 77 (Figure 6) was afforded in high radiochemical purity (>98%) and 15% RCY after a total synthesis time of 98 min, successfully introducing a 'minimalist' protocol for 18 F-synthesis by taking advantage of the onium salt precursor [29].…”

18F-Labeled magnetic nanovectors for bimodal cellular imaging

“…[19][20][21] To this end, multimodal imaging and simultaneous therapy can provide complementary information for precise diagnosis and imaging-guided focused tumor therapy, which points out the need for dual-action probes with integrated imaging and therapeutic functions. Positron emission tomography [22][23][24][25] (PET) using positron emitters such as 11 C, 13 N, 18 F or 68 Ga is widely used in clinical practice for tumor detection or the elucidation of neurological disorders. 23,24,[26][27][28][29][30][31][32][33] Fluor-18 is the most frequently applied radionuclide in diagnosis due to its favorable decay properties with a half-life of 109.8 min and low β +energy and should also be suitable for the labeling of NPs.…”

“…Positron emission tomography [22][23][24][25] (PET) using positron emitters such as 11 C, 13 N, 18 F or 68 Ga is widely used in clinical practice for tumor detection or the elucidation of neurological disorders. 23,24,[26][27][28][29][30][31][32][33] Fluor-18 is the most frequently applied radionuclide in diagnosis due to its favorable decay properties with a half-life of 109.8 min and low β +energy and should also be suitable for the labeling of NPs. 30,[34][35][36][37][38][39][40][41] The common strategies for producing radioactively labeled nanoparticles include either the labeling of the particle core or of the particle shell.…”