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The synthetic bis(zinc(II)-dipicolylamine) (DPAZn2) coordination complexes are known to have a high specific and selective affinity to target the exposed phosphatidylserine (PS) on the surface of dead and dying cells. An (18)F-labeled DPAZn2 complex (4-(18)F-Fluoro-benzoyl-bis(zinc(II)-dipicolylamine), (18)F-FB-DPAZn2) as positron emission tomography (PET) tracer was developed and evaluated for in vivo imaging of tumor treated with a chemical agent. The in vitro cell stain studies revealed that fluorescent DPAZn2 complexes (Dansyl-DPAZn2) stained the same cells (apoptotic and necrotic cells) as fluorescein isothiocyanate (FITC) labeled Annexin V (FITC-Annexin V). The radiosynthesis of (18)F-FB-DPAZn2 was achieved through the amidation the precursor bis(2,2'-dipicolylamine) derivative (DPA2) with the prosthetic group N-succinimidyl-4-[(18)F]-fluorobenzoate ((18)F-SFB) and chelation with zinc nitrate. In the biodistribution study, the fast clearance of (18)F-FB-DPAZn2 from blood and kidney was observed and high uptake in liver and intestine within 90 min postinjection was also found. For the PET imaging, significantly higher tumor uptake of (18)F-FB-DPAZn2 was observed in the adriamycin (ADM)-treated Hepa1-6 hepatocellular carcinoma-bearing mice than that in the untreated tumor-model mice, while a slightly decreased tumor uptake of (18)F-FDG was found in the ADM-treated tumor-bearing mice. The results indicate that (18)F-FB-DPAZn2 has the similar capability of apoptosis detection as FITC-Annexin V and seems to be a potential PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy. The high uptake of (18)F-FB-DPAZn2 in the abdomen needs to optimize the structure for improving its pharmacokinetics characteristics in the future work.

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Semiconductor quantum dots (QDs), after surface modification to provide water solubility and biocompatibility, have a promising future in biomedical applications. In this study, a dual receptortargeting dual-modality PET/near-infrared fluorescence (NIRF) probe was developed for accurate assessment of the pharmacokinetics and tumor-targeting efficacy of QDs. Methods: QDs were modified by b-Glu-RGD-BBN (RGD is arginine-glycine-aspartate acid, and BBN is bombesin) peptides and then labeled with 18 F via the 4-nitrophenyl-2-18 F-fluoropropionate prosthetic group. Cytotoxicity and cell-binding assay of QD-RGD-BBN were performed with PC-3 cells. In vivo dual-modality PET/NIRF imaging of prostate tumor-bearing mice was investigated using QD-RGD-BBN and 2-18 F-fluoropropionyl-QD-RGD-BBN ( 18 F-FP-QD-RGD-BBN). An in vivo biodistribution study of 18 F-FP-QD-RGD-BBN was performed on normal mice. Results: QD-RGD-BBN exhibited strong red luminescence (600-800 nm) with the same maximum fluorescence wavelength (705 nm) as QD705 and slightly lower toxicity than that of QD705 in PC-3 cells at concentrations of greater than 30 mg/mL. Uptake of QD-RGD-BBN in PC-3 cells showed no significant decrease in the presence of an excess amount of dimer arginineglycine-aspartate acid (RGD 2 ) or bombesin(7-14) (BBN) peptide but was blocked significantly in the presence of an excess amount of NH 2 -RGD-BBN. Dual-function PET/NIRF imaging is able to accurately assess the biodistribution and tumor-targeting efficacy of the 18 F-labeled functionalized QDs. Conclusion: The functionalized QD probe has great potential as a universal dual-targeting probe for detecting tumors in living subjects, opening up a new strategy for the development of multitargeting multimodality 18 F-labeled QD probes with improved tumor-targeting efficacy.