Open AccessPET imaging of Hsp90 expression in pancreatic cancer using a new 64Cu-labeled dimeric Sansalvamide A decapeptide
Author(s) -
Xiaohui Wang,
Jun Zhang,
Hubing Wu,
Yumin Li,
Peter S. Conti,
Kai Chen
Publication year - 2018
Publication title -
amino acids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.894
H-Index - 118
eISSN - 1438-2199
pISSN - 0939-4451
DOI - 10.1007/s00726-018-2566-y
Subject(s) - hsp90 inhibitor , biodistribution , in vivo , pancreatic cancer , ex vivo , pancreas , positron emission tomography , heat shock protein , cancer , hsp90 , chemistry , cancer research , imaging agent , in vitro , pathology , microbiology and biotechnology , medicine , nuclear medicine , biochemistry , biology , gene
Heat shock protein 90 (Hsp90) plays a vital role in the progress of malignant disease and elevated Hsp90 expression has been reported in pancreatic cancer. In this study, we radiolabeled a dimeric Sansalvamide A derivative (Di-San A1) with 64 Cu, and evaluated the feasibility of using 64 Cu-Di-San A1 for PET imaging of Hsp90 expression in a mouse model of pancreatic cancer. A macrocyclic chelator NOTA (1,4,7-triazacyclononane-1,4,7-trisacetic acid) was conjugated to Di-San A1. 64 Cu-Di-San A1 was successfully prepared in a radiochemical yield > 97% with a radiochemical purity > 98%. 64 Cu-Di-San A1 is stable in PBS and mouse serum with > 92% of parent probe intact after 4 h incubation. The cell binding and uptake revealed that 64 Cu-Di-San A1 binds to Hsp90-positive PL45 pancreatic cancer cells, and the binding can be effectively blocked by an Hsp90 inhibitor (17AAG). For microPET study, 64 Cu-Di-San A1 shows good in vivo performance in terms of tumor uptake in nude mice bearing PL45 tumors. The Hsp90-specific tumor activity accumulation of 64 Cu-Di-San A1 was further demonstrated by significant reduction of PL45 tumor uptake with a pre-injected blocking dose of 17AAG. The ex vivo PET imaging and biodistribution results were consistent with the quantitative analysis of PET imaging, demonstrating good tumor-to-muscle ratio (5.35 ± 0.46) of 64 Cu-Di-San A1 at 4 h post-injection in PL45 tumor mouse xenografts. 64 Cu-Di-San A1 allows PET imaging of Hsp90 expression in PL45 tumors, which may provide a non-invasive method to quantitatively characterize Hsp90 expression in pancreatic cancer.