The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu 2+-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu 2+ into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing 64 Cu 2+ , positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an "ideal" PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy.

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Vascular endothelial growth factor receptors (VEGFRs) are well recognized as significant biomarkers of tumor angiogenesis. Herein, we have developed a first-of-its-kind peptide-based VEGFR positron emission tomography (PET) tracer. The novel [ 64 Cu]VEGF 125−136 peptide possessed satisfactory radio-characteristics and showed good specificity for the visualization of VEGFR in various mouse models, in which the tumorspecific radioactivity uptake was highly correlated to the VEGFR expression level. Moreover, the tracer showed high tumor uptake (ca. 5.89 %ID/g at 20 min postinjection in B16F10 mice) and excellent pharmacokinetics, achieving the maximum imaging quality within 1 h after injection. These features convey [ 64 Cu]VEGF 125−136 as a promising, clinically translatable PET tracer for the imaging of tumor angiogenesis.

Native peptide-based PET tracers were developed for PD-L1 imaging. The pegylation of the peptide improves the pharmacokinetics and biodistribution of the tracers.

To introduce the 3-[ F]fluoro-2-hydroxypropyl moiety into positron emission tomography (PET) radiotracers, we performed automated synthesis of (rac)-, (R)-, and (S)-[ F]epifluorohydrin ([ F]1) by nucleophilic displacement of (rac)-, (R)-, or (S)-glycidyl tosylate with F and purification by distillation. The ring-opening reaction of (R)- or (S)-[ F]1 with phenol precursors gave enantioenriched [ F]fluoroalkylated products without racemisation. We then synthesised (rac)-, (R)-, and (S)- 2-{5-[4-(3-[ F]fluoro-2-hydroxypropoxy)phenyl]-2-oxobenzo[d]oxazol-3(2H)-yl}-N-methyl-N-phenylacetamide ([ F]6) as novel radiotracers for the PET imaging of translocator protein (18 kDa) and showed that (R)- and (S)-[ F]6 had different radioactivity uptake in mouse bone and liver. Thus, (rac)-, (R)-, and (S)-[ F]1 are effective radiolabelling reagents and can be used to develop PET radiotracers by examining the effects of chirality on their in vitro binding affinities and in vivo behaviour.

Leveraging interface peptides in PD-L1 for PET imaging of PD-1, providing a new paradigm for radiotracer development.

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BackgroundHistamine H3 receptor (H3R) is a potential therapeutic target of sleep- and cognition-related disorders. The purpose of the present study is to develop a novel positron emission tomography (PET) ligand for H3Rs from dihydroquinolinone derivatives, which we previously found to have high affinity with these receptors.MethodsSix compounds were selected from a dihydroquinolinone compound library based on structural capability for 11C labeling and binding affinity for H3Rs. Their in vivo kinetics in the rat brain were examined in a comparative manner by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Chemicals with appropriate kinetic properties were then labeled with 11C and evaluated in rats and monkeys using PET.ResultsOf the six compounds, TASP0410457 (also diminutively called TASP457) and TASP0434988 exhibited fast kinetics and relatively high brain uptakes in ex vivo LC-MS/MS and were selected as candidate PET imaging agents. PET data in rat brains were mostly consistent with LC-MS/MS findings, and rat and monkey PET scans demonstrated that [11C]TASP0410457 was superior to [11C]TASP0434988 for high-contrast H3R PET imaging. In the monkey brain PET, distribution volume for [11C]TASP0410457 could be quantified, and receptor occupancy by a nonradioactive compound was measurable using this radioligand. The specific binding of [11C]TASP0410457 to H3Rs was confirmed by autoradiography using rat and monkey brain sections.ConclusionsWe developed [11C]TASP0410457 as a radioligand enabling a robust quantification of H3Rs in all brain regions and demonstrated the utility of ex vivo LC-MS/MS and in vivo PET assays for selecting appropriate imaging tracers. [11C]TASP0410457 will help to examine the implication of H3Rs in neuropsychiatric disorders and to characterize emerging therapeutic agents targeting H3Rs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0170-2) contains supplementary material, which is available to authorized users.