DH-Mammo PET: a dual-head positron emission mammography system for breast imaging.

Objective. To develop a simultaneous positron emission tomography-Optical (OPET) breast imaging dual-head PET subsystem, called DH-Mammo PET, for accurate, early diagnosis and efficacy assessment of breast cancer with high resolution and sensitivity.Approach. We developed a breast-dedicated PET based on LYSO crystal, silicon photomultiplier array and multi-voltage threshold sampling technique. It consists of two detector heads, each with a detection area of 216 mm × 145.5 mm. The distance between the detector heads is fixed at 120 mm. In order to extract coincidences and correct data, GPU-based software coincidence processing, random, scatter, normalization, gap-filling and attenuation corrections were applied in turn. The images were reconstructed using maximum likelihood expectation maximization with depth of interaction (DOI) modeling. The performance of DH-Mammo PET was evaluated referring to NEMA NU 4-2008, NU 2-2007 and Chinese industry recommended standard YY/T 1835-2022. Besides, several clinical patient images of DH-Mammo PET were compared with those of a whole-body PET/CT.Main results. The energy resolution was 14.5%, and time resolution was < 1.31 ns. Indicated by the22Na point source imaging, its spatial resolution was 2.60 mm (5.40 mm), 1.00 mm (1.04 mm), and 0.96 mm (0.93 mm) in theX,YandZdirections, respectively, using the system response matrix with (without) DOI modeling. Indicated by the Derenzo phantom imaging, the spatial resolution was ∼3.0 mm, <1.2 mm, and <1.2 mm in theX,YandZdirections. The system sensitivity was 6.87%, 4.89% and 3.37% with an energy window of 100-800, 250-750 and 350-650 keV, respectively. The scatter fraction was 26.43%, and the peak NECR was 162.6 kcps at 24.1 MBq for the modified rat-like phantom. As for the recovery coefficients, they ranged from 0.15 to 1.04 for rods between 1 and 5 mm obtained with a NEMA image quality phantom. The spill-over ratio for the air-filled and water-filled chamber was 0.05 and 0.11, respectively. DH-Mammo PET can provide more image details in clinical experiments and fulfil a fast scan with 60-120 s acquisition time.Significance. Good spatial resolution and high sensitivity of DH-Mammo PET would enable fast and accurate PET imaging of the breast. Besides, combining the DH-Mammo PET with the diffuse optical tomography would make full use of tumor metabolic imaging and tissue endogenous optical imaging, which would improve the accuracy of early clinical diagnosis of small lesions of breast cancers.

18F-Labeled BODIPY Dye: A Potential Prosthetic Group for Brain Hybrid PET/Optical Imaging Agents.

There are few hybrid positron emission tomography (PET)/fluorescence imaging agents available for brain imaging. For this purpose, BODIPY dye is very attractive because one of its fluorine atoms can be readily exchanged with 18F, and it can be modified to produce red-shifted fluorescence. In this study, therefore, we synthesized and investigated a 18F-labeled red-shifted BODIPY dye as a prosthetic group for brain hybrid PET/optical imaging agents and determined the optimal dose of this radioligand for hybrid imaging. The red-shifted BODIPY dye (1) was synthesized, and one of its fluorine atoms was exchanged with 18F using SnCl4 in high yield. Partition coefficients of 18F-labeled BODIPY dye ([18F]1) and 1 were measured using its radioactivity and fluorescence, respectively, which were shown to be suitable for brain penetration. Optimal dose for hybrid imaging was determined by analysis of PET/CT and optical images of Balb/C nude mice injected with [18F]1 and 1, respectively. Hybrid PET/optical images of mice injected with optimal dose of [18F]1 showed strong radioactivity and fluorescence signal in the brain at 2 min after injection, with rapid clearance by 30 min. Tissue distribution data confirmed the in vivo and ex vivo PET/optical imaging data, indicating desirable brain pharmacokinetics of the radioligand. Taken together, the results of this study suggest that [18F]1 can be widely used as a prosthetic group for brain hybrid PET/optical imaging agents.

Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). (64)Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than (64)Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but (64)Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates.

Hybrid PET/optical imaging of integrin αVß3 receptor expression using a (64)Cu-labeled streptavidin/biotin-based dimeric RGD peptide.

BACKGROUND: Hybrid PET/optical imaging provides quantitative and complementary information for diagnosis of tumors. Herein, we developed a (64)Cu-labeled AlexaFluor 680-streptavidin ((AF)SAv)/biotin-based dimeric cyclic RGD peptide (RGD2) for hybrid PET/optical imaging of integrin αVß3 expression. METHODS: (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-(AF)SAv/biotin-PEG-RGD2 was prepared by formation of a complex comprising DOTA-(AF)SAv and biotin-PEG-RGD2, followed by radiolabeling with (64)Cu. Receptor binding studies of DOTA-(AF)SAv/biotin-PEG-RGD2 were performed using U87MG cells and (125)I-RGDyK as the radioligand, and cellular uptake studies of (64)Cu-DOTA-(AF)SAv/biotin-PEG-RGD2 were also performed. MicroPET imaging followed by optical imaging of U87MG tumor-bearing mice was acquired after injection of the hybrid probe, and region of interest (ROI) analysis of tumors was performed. Ex vivo PET/optical imaging and biodistribution studies of the major tissues were performed after the in vivo imaging, and immunofluorescence staining of the tumor tissue sections was carried out. RESULTS: (64)Cu-DOTA-(AF)SAv/biotin-PEG-RGD2 was prepared in 52.1 ± 5.4 % radiochemical yield and with specific activity of 1.0 ± 0.1 GBq/mg. Receptor binding studies showed that DOTA-(AF)SAv/biotin-PEG-RGD2 had higher binding affinity for integrin αVß3 than RGD2, reflecting a possible polyvalency effect. Moreover, the hybrid probe revealed time-dependent uptake by U87MG cells. In a microPET/optical imaging study, the hybrid probe demonstrated high accumulation in tumors; ROI analysis revealed 2.7 ± 0.2 % ID/g at 1 h and 4.7 ± 0.2 % ID/g at 21 h after injection, and subsequently acquired optical images showed tumors with strong fluorescence intensity. Ex vivo PET/optical images of the major tissues confirmed the in vivo imaging data, and biodistribution studies demonstrated high and specific uptake in tumors (4.8 ± 0.1 % ID/g). Immunofluorescence staining showed the formation of new blood vessels in tumor tissues, suggesting that the tumor uptake was due to specific binding of the hybrid probe to integrin αVß3 expressed on tumor cells. CONCLUSIONS: These results indicate that a (64)Cu-DOTA-(AF)SAv/biotin-PEG-RGD2 is able to provide quantitative information on hybrid PET/optical imaging of integrin αVß3 expression.