Chelator-Free Labeling of Layered Double Hydroxide Nanoparticles for in Vivo PET Imaging.

Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation (64)Cu(2+) and trivalent cation (44)Sc(3+) were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation (89)Zr(4+) could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with (64)Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.

Generation and screening of monoclonal antibodies for immunoPET imaging of IGF1R in prostate cancer.

Insulin-like growth factor 1 receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. The expression level of IGF1R is related to resistance to several targeted therapies. The goal of this study was to develop an immunoPET tracer for imaging of IGF1R in prostate cancer. Murine antibodies against human IGF1R were generated in BALB/c mice, which were screened in IGF1R-positive MCF-7 cells using flow cytometry as well as biodistribution studies with multiple (64)Cu-labeled antibody clones. The antibody production method we adopted could readily produce milligram quantities of anti-IGF1R antibodies for in vivo studies. One antibody clone (1A2G11) with the highest affinity for IGF1R was selected and conjugated to NOTA for (64)Cu-labeling. NOTA-1A2G11 maintained IGF1R specificity/avidity based on flow cytometry. (64)Cu-labeling was achieved with good yield (>50%) and high specific activity (>1 Ci/µmol). Serial PET imaging revealed that uptake of (64)Cu-NOTA-1A2G11 was 2.8 ± 0.7, 10.2 ± 2.6, and 9.6 ± 1.7 %ID/g in IGF1R-positive DU-145 tumors at 4, 24, and 48 h postinjection, respectively (n = 3), significantly higher than that in IGF1R-negative LNCaP tumors (<3 %ID/g at each time point) except at 4 h postinjection. Histology studies showed strong correlations between IGF1R expression level in the prostate cancer tumor tissues and tumor uptake of (64)Cu-NOTA-1A2G11. Prominent, persistent, and IGF1R-specific uptake of (64)Cu-NOTA-1A2G11 in IGF1R-positive prostate tumors holds strong potential for future cancer diagnosis, prognosis, and therapy using this antibody.