Evaluation of Pan-SSTRs Targeted Radioligand [⁶⁴Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice

Abstract

64Cu-labeled new pan-somatostatin receptors (pan-SSTRs) probe PA1 was synthesized, characterized, and evaluated by in vitro and in vivo experiments. [64Cu]­NOTA-PA1 was obtained with high specific activity, high radiochemical purity, and good stability. Cell uptake of [64Cu]­NOTA-PA1 was higher than that of [64Cu]­DOTA-TATE in MCF-7, A549, BGC823, and HT-29 cell lines. [64Cu]­NOTA-PA1 showed high binding affinity for SSTRs expressed in A549 cells. The in vivo biodistribution and micropositron emission tomography (micro-PET) imaging studies of [64Cu]­NOTA-PA1 revealed good detection ability in MCF-7 and A549 xenografted nude mice. The radiosynthesis, quality control, and preliminary biological evaluation of [64Cu]­NOTA-PA1 have broaden the application of radiolabeled octreotide for SSTRs imaging, which could act as a potential multisubtypes targeted radiotracer for imaging SSTRs-positive tumors.

PET imaging of [ 52 Mn]Mn-DOTATATE and [ 52 Mn]Mn-DOTA-JR11

“…3A). Similar uptake values have been reported by Liu et al using [ 64 Cu]Cu-DOTATATE in MCF7 (0.9 ± 0.06% AD/10 6 cells) and A549 (0.81 ± 0.21% AD/10 6 ) [24]. Cell uptake studies comparing [ 52 Mn]Mn-DOTATATE and [ 52 Mn]Mn-DOTA-JR11 in AR42J cell line showed that both radiotracers exhibited a nity for SSTR2.…”

Dilute lattice doping of 64Cu into 2D-nanoplates: its impact on radio-labeling efficiency and stability for target selective PET imaging

“…57 For 64 Cu-NOTA-PA1 formed by conjugating 64 Cu-NOTA with a pasireotide derivative (PA1), its intercellular uptake efficiency was only 3.67 AE 0.36 and 2.97 AE 0.09% at 2 h on human breast cancer (MCF-7) and human lung cancer (A549) cell lines, respectively. 58 In the case of 64 Cu-Sur-NGR2, the 64 Cu-labeled dimeric NGR (asparagineglycine-arginine) peptide based on the sarcophagine (Sur) cage, its uptake value was observed to be 0.72 AE 0.01 and 1.72 AE 0.24% upon treating on the human fibrosarcoma (HT-1080) cell line at 1 h and 2 h, respectively, after incubation. 59 We, therefore, came up with a conclusion that our designed samples, 64 Cu-QT-NPs and 64 Cu-QT-NPs/BSA, can be a promising radioisotope delivery and imaging technology platform not only because of their high labeling efficiency and excellent chemical stability, but also because of their extremely high biocompatibility and low toxicity.…”

Targeted paclitaxel‐octreotide conjugates inhibited the growth of paclitaxel‐resistant human non‐small cell lung cancer A549 cells in vitro

“… 8 Somatostatin receptors (SSTRs) are a group of G‐protein‐coupled receptors that have been characterized in different types of cancer, including NSCLC. 9 SSTRs are found to be overexpressed in human NSCLC by radio‐labeled analogues of somatostatin 10 , 11 and therefore, it could serve as potential targets for treatment. Cytotoxic somatostatin analogues containing doxorubicin or 2‐pyrrolino‐doxorubicin have been evaluated for treatment of colorectal cancer, 12 breast cancer, 13 glioblastoma, 14 etc.…”