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Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies. Non‐invasive molecular imaging techniques, such as Positron Emission Tomography (PET), using radiolabeled mAbs provide useful information on the whole‐body distribution of the biomolecules, which may enable patient stratification, diagnosis, selection of targeted therapies, evaluation of treatment response, and prediction of dose limiting tissue and adverse effects. In addition, when mAbs are labeled with therapeutic radionuclides, the combination of immunological and radiobiological cytotoxicity may result in enhanced treatment efficacy. The pharmacokinetic profile of antibodies demands the use of long half‐life isotopes for longitudinal scrutiny of mAb biodistribution and precludes the use of well‐stablished short half‐life isotopes. Herein, we review the most promising PET radiometals with chemical and physical characteristics that make the appealing for mAb labeling, highlighting those with theranostic radioisotopes. [ABSTRACT FROM AUTHOR]

Nanomaterials with renal clearance from the body within a reasonable timescale have shown great promises in the area of nanomedicine recently. However, the integration of theranostic and renal clearance properties into a single ultrasmall nanostructure remains a great challenge. Herein, meso-tetra(4-carboxyphenyl)porphyrin (TCPP) structure is utilized as a model, for the first time using noninvasive dynamic positron emission tomography (PET) imaging to investigate the balance of the renal clearance and tumor uptake behaviors of polyethylene glycol (PEG)-modified porphyrin nanoparticles (TCPP-PEG) with various molecular weights. This study finds that TCPP-PEG nanoparticles with larger molecular weight show higher tumor uptake due to the enhanced permeability and retention effect, while the lower ones tend to be better for renal clearance. Based on dynamic PET and fluorescence dual-modal imaging modalities, the TCPP-PEG10K nanoparticles seem to be an excellent choice for the balance of renal clearance and tumor retention. In vitro and in vivo photodynamic therapy confirms an excellent therapeutic efficacy. Therefore, this work presents a simplified approach to fabricate and select biocompatible multifunctional TCPP-PEG-based theranostic agents with renal clearance behavior, which highlights the clinical application potential of TCPP-PEG nanoparticles as theranostic probes for imaging-guided cancer therapy. [ABSTRACT FROM AUTHOR]

Multifunctional theranostic agents have become rather attractive to realize image-guided combination cancer therapy. Herein, a novel method is developed to synthesize Bi2Se3 nanosheets decorated with mono-dispersed FeSe2 nanoparticles (FeSe2/Bi2Se3) for tetra-modal image-guided combined photothermal and radiation tumor therapy. Interestingly, upon addition of Bi(NO3)3, pre-made FeSe2 nanoparticles via cation exchange would be gradually converted into Bi2Se3 nanosheets, on which remaining FeSe2 nanoparticles are decorated. The yielded FeSe2/Bi2Se3 composite-nanostructures are then modified with polyethylene glycol (PEG). Taking advantages of the high r2 relaxivity of FeSe2, the X-ray attenuation ability of Bi2Se3, the strong near-infrared optical absorbance of the whole nanostructure, as well as the chelate-free radiolabeling of 64Cu on FeSe2/Bi2Se3-PEG, in vivo magnetic resonance/computer tomography/photoacoustic/position emission tomography multimodal imaging is carried out, revealing efficient tumor homing of FeSe2/Bi2Se3-PEG after intravenous injection. Utilizing the intrinsic physical properties of FeSe2/Bi2Se3-PEG, in vivo photothermal and radiation therapy to achieve synergistic tumor destruction is then realized, without causing obvious toxicity to the treated animals. This work presents a unique method to synthesize composite-nanostructures with highly integrated functionalities, promising not only for nano-biomedicine but also potentially for other different nanotechnology fields. [ABSTRACT FROM AUTHOR]

Abstract We present a simplified, automatable single-column radiochemical separation method using the extraction chromatographic branched-DGA resin for the production of no-carrier-added 86Y with a radiochemical yield higher than 95%, an apparent molar activity of 1.4 ± 0.4 Ci/μmol (DOTA) and 2.3 ± 0.7 Ci/μmol (DTPA), and a run-to-run recycling efficiency of the isotopically-enriched target of 98 ± 1%. These results enable the preparation of 86Y radiopharmaceuticals for 86Y/90Y-based cancer theranostic applications. Highlights • Simple radiochemical separation using single column extraction chromatography. • Separation strategy for production of high-quality theranostic Y-86 applications. • Process allows for high recycling efficiency of the enriched target material. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoshell (MSN) coating has been demonstrated as a versatile surface modification strategy for various kinds of inorganic functional nanoparticles, such as gold nanorods (GNRs), to achieve not only improved nanoparticle stability but also concomitant drug loading capability. However, limited drug loading capacity and low tumor accumulation rate in vivo are two major challenges for the biomedical applications of MSN-coated GNRs (GNR@MSN). In this study, by coating uniformly sized GNRs with MSN in an oil-water biphase reaction system, we have successfully synthesized a new bacteria-like GNR@MSN (i.e., bGNR@MSN) with a significantly enlarged pore size (4–8 nm) and surface area (470 m 2 /g). After PEGylation and highly efficient loading of doxorubicin (DOX, 40.9%, w/w), bGNR@MSN were used for positron emission tomography (PET, via facile and chelator-free 89 Zr-labeling) and photoacoustic imaging-guided chemo-photothermal cancer therapy in vivo . PET imaging showed that 89 Zr-labeled bGNR@MSN(DOX)-PEG can passively target to the 4T1 murine breast cancer-bearing mice with high efficiency (∼10 %ID/g), based on enhanced permeability and retention effect. Significantly enhanced chemo-photothermal combination therapy was also achieved due to excellent photothermal effect and near-infrared-light-triggered drug release by bGNR@MSN(DOX)-PEG at the tumor site. The promising results indicate great potential of bGNR@MSN-PEG nanoplatforms for future cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Although various types of imaging agents have been developed for photoacoustic (PA) imaging, relatively few imaging agents exhibit high selectivity/sensitivity to the tumor microenvironment for on-demand PA imaging and therapy. Herein, molybdenum-based polyoxometalate (POM) clusters with the highest oxidation state of Mo(VI) (denoted as Ox-POM) were designed as novel agents for redox-activated PA imaging-guided photothermal therapy. Capable of escaping from recognition and capture by the liver and spleen, these renal clearable clusters with ultrasmall size (hydrodynamic size: 1.9 nm) can accumulate in the tumor, self-assemble into larger nanoclusters at low pH, and are reduced to NIR absorptive agents in the tumor microenvironment. Studies in 4T1 tumor-bearing mice indicated that these clusters could be employed for bioresponsive PA imaging-guided tumor ablation in vivo. Our finding is expected to establish a new physicochemical paradigm for the design of PA imaging agents based on clusters, bridging the conventional concepts of "molecule" and "nano" in the bioimaging field. [ABSTRACT FROM AUTHOR]