We report the direct synthesis of strong, highly conducting, and transparent single-walled carbon nanotube (SWNT) films. Systematically, tests reveal that the directly synthesized films have superior electrical and mechanical properties compared with the films made from a solution-based filtration process: the electrical conductivity is over 2000 S/cm and the strength can reach 360 MPa. These values are both enhanced by more than 1 order. We attribute these intriguing properties to the good and long interbundle connections. Moreover, by the help of an extrapolated Weibull theory, we verify the feasibility of reducing the interbundle slip by utilizing the long-range intertube friction and estimate the ultimate strength of macroscale SWNTs without binding agent.Because of their optical transparency and unique electric properties together with mechanical flexibility, film-like single-walled carbon nanotubes (SWNTs) are attractive not only for fundamental researches but also potential applications. For example, large optical nonlinearity, 1 subpicosecond optical response 2,3 and bolometric infrared photoresponse 4 have been observed in SWNT films, and the feasibilities of using SWNT films or networks as sensors, 5,6 diodes, 7 and field effect transistors 8 have already been demonstrated. Recently, highly conducting transparent SWNT films (tSWNTs) have also been fabricated by a kind of controlled filtration-deposition process, 9 which could be used as transparent electrodes for GaN/InGaN or flexible organic lightemitting diodes. 10,11 However, almost all of the above reports focused on the post-treated SWNT films, which are obtained through solution-based filtration processes. As known, to obtain high conductivity, SWNTs must be well purified and dispersed from sootlike morphology, which usually costs several days and leaves unrecyclable chemical residues. Besides, the comparative low strength of these films is one of the challenges for their applications, especially in the field of high-strength enforcement sheets.Here we report the direct synthesis of strong, highly conducting, and transparent films through a further developed floating catalyst CVD (FCCVD) technique that is based on the methods of producing large-scale nonwoven SWNTs. 12 As catalyst source, ferrocene/sulfur powder is heated to 65-85°C and flowed into a reaction zone by the mixture of 1000 sccm argon and 1-8 sccm methane. The growth rates of the films are mainly determined by the sublimation rate of the catalysts. Under typical conditions, after 30 min growth, thin films with a thickness of 100 nm will form in the high-temperature zone (over 600°C) of the quartz tube and can be easily peeled off. This type of large-area freestanding film can be easily handled for further researches. Raman scattering and HRTEM images show that most CNTs in the films are single-walled carbon nanotubes. In this paper, we systematically investigated the properties of the directly

It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle4-cyclo[Asp5-His-D-Phe7-Arg-Trp-Lys10]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT). The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET). We designed and synthesized three peptides, DOTA-PEG2-Nle-CycMSHhex (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSHhex (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSHhex (CCZ01056). All three peptides exhibited high binding affinity to MC1R with sub-nanomolar Ki values, rapid internalization into B16F10 melanoma cells and high in vivo stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma. All three 68Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048). Due to high accumulation at tumor sites and rapid background clearance of 68Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased. Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively. A blocking study was also performed by co-injection of excess amount of non-radioactive Ga-coupled of CCZ01048, which confirmed that the tumor uptake was MC1R mediated. In conclusion, the introduction of a cationic Pip linker to Nle-CycMSHhex, CCZ01048, not only improved tumor uptake, but also generated high tumor-to-normal tissue contrast with PET imaging in a preclinical melanoma model. Therefore, CCZ01048 is a promising candidate for PET imaging of melanoma, and potentially as a theranostic agent for radionuclide therapy of melanoma when labeled with α or β emitters.

We designed and evaluated a novel albuminbinder-conjugated 177 Lu-PSMA-617 derivative, 177 Lu-HTK01169, with an extended blood retention time to maximize the radiation dose delivered to prostate tumors expressing prostate-specific membrane antigen (PSMA). PSMA-617 and HTK01169 that contained N-[4-(p-iodophenyl)butanoyl]-Glu as an albuminbinding motif were synthesized using the solid-phase approach. Binding affinity to PSMA was determined by in vitro competition-binding assay. 177 Lu labeling was performed in acetate buffer (pH 4.5) at 90 °C for 15 min. SPECT/CT imaging, biodistribution, and endoradiotherapy studies were conducted in mice bearing PSMA-expressing LNCaP tumor xenografts. Radiation dosimetry was calculated using OLINDA software. Lu-PSMA-617 and Lu-HTK01169-bound PSMA with high affinity (K i values = 0.24 and 0.04 nM, respectively). SPECT imaging and biodistribution studies showed that 177 Lu-PSMA-617 and 177 Lu-HTK01169 were excreted mainly via the renal pathway. With fast blood clearance (0.68%ID/g at 1 h postinjection), the tumor uptake of 177 Lu-PSMA-617 peaked at 1 h postinjection (15.1%ID/g) and gradually decreased to 7.91%ID/g at 120 h postinjection. With extended blood retention (16.6 and 2.10%ID/g at 1 and 24 h, respectively), the tumor uptake of 177 Lu-HTK01169 peaked at 24 h postinjection (55.9%ID/g) and remained at the same level by the end of the study (120 h). Based on dosimetry calculations, 177 Lu-HTK01169 delivered an 8.3-fold higher radiation dose than 177 Lu-PSMA-617 to LNCaP tumor xenografts. For the endoradiotherapy study, the mice treated with 177 Lu-PSMA-617 (18.5 MBq) all reached humane end point (tumor volume >1000 mm 3 ) by Day 73 with a median survival of 58 days. Mice treated with 18.5, 9.3, 4.6, or 2.3 MBq of 177 Lu-HTK01169 had a median survival of >120, 103, 61, and 28 days, respectively. With greatly enhanced tumor uptake and treatment efficacy compared to 177 Lu-PSMA-617 in preclinical studies, 177 Lu-HTK01169 warrants further investigation for endoradiotherapy of prostate cancer.

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Unsolvated, trinuclear, homometallic, rare-earth-metal multimethyl methylidene complexes [{(NCN)Ln(μ(2)-CH(3))}(3)(μ(3)-CH(3))(μ(3)-CH(2))] (NCN = L = [PhC{NC(6)H(4)(iPr-2,6)(2)}(2)](-); Ln = Sc (2a), Lu (2b)) have been synthesized by treatment of [(L)Ln{CH(2)C(6)H(4)N(CH(3))(2)-o}(2)] (Ln = Sc (1a), Lu (1b)) with two equivalents of AlMe(3) in toluene at ambient temperature in good yields. Treatment of 1 with three equivalents of AlMe(3) gives the heterometallic trinuclear complexes [(L)Ln(AlMe(4))(2)] (Ln = Sc (3a), Lu (3b)) in good yields. Interestingly, 2 can also be generated by recrystallization of 3 in THF/toluene, thereby indicating that the THF molecule can also induce C-H bond activation of 2. Reaction of 2 with one equivalent of ketones affords the trinuclear homometallic oxo-trimethyl complexes [{(L)Ln(μ(2) -CH(3))}(3) (μ(3)-CH(3))(μ(3)-O)] (Ln = Sc(4a), Lu(4b)) in high yields. Complex 4b reacts with one equivalent of cyclohexanone to give the methyl abstraction product [{(L)Lu(μ(2) -CH(3) )}(3) (μ(3) -OC(6)H(9))(μ(3)-O)] (5b), whereas reaction of 4b with acetophenone forms the insertion product [{(L)Lu(μ(2)-CH(3))}(3){μ(3)-OCPh(CH(3))(2)}(μ(3)-O)] (6b). Complex 4a is inert to ketone under the same conditions. All these new complexes have been characterized by elemental analysis, NMR spectroscopy, and confirmed by X-ray diffraction determination.

Carbonic anhydrase IX (CA-IX), a transmembrane enzyme, mediates cell survival under hypoxic conditions and is overexpressed in solid malignancies. In this study, we synthesized four 18 F sulfonamide derivatives and evaluated their potential for imaging CA-IX expression with PET. Methods: Azide derivatives of 2 carbonic anhydrase inhibitors, 4-(2-aminoethyl)benzenesulfonamide (AEBS) and 4-aminobenzensulfonamide (ABS), were coupled to radiosynthons with either 1 or 3 alkynes and a pendent ammoniomethyltrifluoroborate (AmBF 3 ) to generate monovalent or trivalent enzyme inhibitors. Binding affinity to CA-IX and other CA isoforms was determined via a stopped-flow, CA-catalyzed CO 2 hydration assay. Tracers were radiolabeled via 18 F-19 F isotope exchange reactions. Imaging/biodistribution studies were performed using HT-29 tumor-bearing immunocompromised mice. Results: Monomeric AmBF 3 -AEBS and AmBF 3 -ABS were obtained in 41% and 40% yields, whereas trimeric AmBF 3 -(AEBS) 3 and AmBF 3 -(ABS) 3 were obtained in 47% and 55% yields, respectively. Derivatives bound CA-I, -II, -IX, and -XII with good affinity (0.49-100.3 nM). 18 F-labeled sulfonamides were obtained in 16.3%-36.8% non-decay-corrected radiochemical yields, with 40-207 GBq/ mmol specific activity and greater than 95% radiochemical purity. Biodistribution/imaging studies showed that the tracers were excreted through both renal and hepatobiliary pathways. At 1 h after injection, HT-29 tumor xenografts were clearly visualized in PET images with modest contrast for all 4 tracers. Tumor uptake was 2-fold higher for monovalent tracers (∼0.60 percentage injected dose per gram [%ID/g]) than for trivalent tracers (∼0.30 %ID/g); however, tumor-to-background ratios were significantly better for 18 F-AmBF 3 -(ABS) 3 . Preblocking with acetazolamide reduced more than 80% uptake of 18 F-AmBF 3 -(ABS) 3 in HT-29 tumors. Conclusion: Our data suggest that trimerization of an otherwise nonspecific CA inhibitor greatly enhances the selectivity for CA-IX in vivo and represents a promising strategy for creating multivalent enzyme inhibitors for selectively imaging extracellular enzyme activity by PET.

Bradykinin B1 receptor (B1R) is involved in pain and inflammation pathways and is upregulated in inflamed tissues and cancer. Due to its minimal expression in healthy tissues, B1R is an attractive target for the development of therapeutic agents to treat inflammation, chronic pain, and cancer. The goal of this study is to synthesize and compare two (18)F-labeled peptides derived from potent B1R antagonists B9858 and B9958 for imaging B1R expression with positron emission tomography (PET). Azidoacetyl-B9858 2 and azidoacetyl-B9958 3 were synthesized by a solid-phase approach and subsequently clicked to ammoniomethyl-trifluoroborate (AmBF3)-conjugated alkyne 1 to obtain AmBF3-B9858 and AmBF3-B9958, respectively. AmBF3-B9858 and AmBF3-B9958 bound B1R with high affinity, with Ki values at 0.09 ± 0.08 and 0.46 ± 0.03 nM, respectively, as measured by in vitro competition binding assays. (18)F labeling was performed via an (18)F-(19)F isotope exchange reaction. The radiofluorinated tracers were obtained within a synthesis time of 30 min and with 23-32% non-decay-corrected radiochemical yield, >99% radiochemical purity, and 43-87 GBq/μmol specific activity at the end of the synthesis. PET imaging and biodistribution studies were carried out in mice bearing both B1R-positive (B1R(+)) HEK293T::hB1R and B1R-negative (B1R(-)) HEK293T tumors. Both tracers cleared rapidly from most organs/tissues, mainly through the renal pathway. High uptake in B1R(+) tumors ((18)F-AmBF3-B9858: 3.94 ± 1.24% ID/g, tumor-to-muscle ratio 21.3 ± 4.33; (18)F-AmBF3-B9958: 4.20 ± 0.98% ID/g, tumor-to-muscle ratio 48.6 ± 10.7) was observed at 1 h postinjection. These results indicate that (18)F-AmBF3-B9858 and (18)F-AmBF3-B9958 are promising agents for the in vivo imaging of B1R expression with PET.