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Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for 18 F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, 18 F-labeled fluoroalkylphosphonium derivatives ( 18 F-FATPs), including (5-18 F-fluoropentyl)triphenylphosphonium cation ( 18 F-FPTP), (6-18 F-fluorohexyl)triphenylphosphonium cation ( 18 F-FHTP), and (2-(2-18 F-fluoroethoxy)ethyl)triphenylphosphonium cation ( 18 F-FETP), were synthesized. The myocardial extraction and image quality of the 18 F-FATPs were compared with those of 13 N-NH 3 in rat models. Methods: The first-pass extraction fraction (EF) values of the 18 F-FATPs ( 18 F-FPTP, 18 F-FHTP, 18 F-FETP) and 13 N-NH 3 were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of 18 F-FATPs and 13 N-NH 3. To determine pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of the 18 F-FATPs and 13 N-NH 3 were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of 18 F-FATPs and 13 N-NH 3. Results:The EF values of 18 F-FATPs and 13 N-NH 3 were comparable at low flow velocity (0.5 mL/min), whereas at higher flows EF values of 18 F-FATPs were significantly higher than those of 13 N-NH 3 (4.0, 8.0, and 16.0 mL/min, P , 0.05). Myocardium-to-liver ratios of 18 F-FPTP, 18 F-FHTP, 18 F-FETP, and 13 N-NH 3 were 2.10 ± 0.30, 4.36 ± 0.20, 3.88 ± 1.03, and 0.70 ± 0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00 ± 0.25, 4.33 ± 0.20, 7.98 ± 1.23, and 2.26 ± 0.14, respectively. Although 18 F-FATPs and 13 N-NH 3 sharply delineated myocardial perfusion defects, defect size on the 13 N-NH 3 images was significantly smaller than on the 18 F-FATP images soon after tracer injection (0-10 min, P 5 0.027). Conclusion: 18 F-FATPs exhibit higher EF values and more rapid clearance from the liver and lung than 13 N-NH 3 in normal rats, which led to excellent image quality in a rat model of coronary occlusion. Therefore, 18 FFATPs are promising new PET radiopharmaceuticals for myocardial perfusion imaging.

Monobodies are binding scaffold proteins originating from a human fibronectin domain III (Fn3) scaffold that can be easily engineered with specificity and affinity. Human EphA2 (hEphA2) is an early detection marker protein for various tumors including lung, breast, and colon cancer. In this study, we isolated two hEphA2-specific monobodies (E1 and E10) by screening a yeast surface display library. They showed the same amino acid sequence except in the DE loop and had high affinity (~2 nM Kd) against hEphA2. E1 bound only hEphA2 and mEphA2, although it bound hEphA2 with an affinity 2-fold higher than that of mEphA2. However, E10 also bound the mEphA6 and mEphA8 homologs as well as hEphA2 and mEphA2. Thus, E1 but not E10 was highly specific for hEphA2. E1 specifically bound human cells and xenograft tumor tissues expressing hEphA on the cell surface. In vivo optical imaging showed strong targeting of Cy5.5-labeled E1 to mouse tumor tissue induced by PC3 cells, a human prostate cancer cell line that expresses a high level of hEphA2. In conclusion, the highly specific monobody E1 is useful as a hEphA2 probe candidate for in vivo diagnosis and therapy.

X-ray-induced acoustic computed tomography (XACT) has shown great potential as a hybrid imaging modality for real-time non-invasive x-ray dosimetry and low-dose three-dimensional (3D) imaging. While promising, one drawback of the XACT system is the underlying low signal-to-noise ratio (SNR), limiting its in vivo clinical use. In this Letter, we propose the first use of a conventional x-ray computed tomography contrast agent, Gastrografin, for improving the SNR of in situ XACT imaging. We obtained 3D volumetric XACT images of a mouse's stomach with orally injected Gastrografin establishing the proposal's feasibility. Thus, we believe, in the future, our proposed technique will allow in vivo imaging and expand or complement conventional x-ray modalities, such as radiotherapy and accelerators.