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Gastric cancer (GC) is a common cancer worldwide, with high incidence and mortality rates. Therefore, early and precise diagnosis is critical to improving GC prognosis. Tumor-associated myeloid cells infiltrate the tumor microenvironment (TME) and can produce immunosuppressive effects in the early stage of the tumor. The surface integrin receptor CD11b is widely expressed in the specific subsets of myeloid cells, and it has the characteristics of high abundance, high specificity, and high potential for targeted immunotherapy. In this study, two strategies for labeling anti-CD11b, including 89Zr-DFO-anti-CD11b and pretargeted imaging (68Ga-NOTA-polypeptide-PEG11-Tz/anti-CD11b-TCO), were used to evaluate the value of early diagnosis of GC and confirm the advantages of the pretargeted strategy for the diagnosis of GC. Pretargeted molecular probe 68Ga-NOTA-polypeptide-PEG11-Tz was synthesized. The binding affinity of the Tz-radioligand to CD11b was evaluated in vitro, and its blood pharmacokinetic test was performed in vivo. Moreover, the anti-CD11b antibody was conjugated with a p-isothiocyanatobenzyl-desferrioxamine (SCN-DFO) chelator and radiolabeled with zirconium-89. Biodistribution and positron-emission computed tomography imaging experiments were performed in MGC-803 tumor-bearing model mice to evaluate the value of the early diagnosis of GC. Histological evaluation of MGC-803 tumors was conducted to confirm the infiltration of the GC TME with CD11b+ myeloid cells. 68Ga-NOTA-polypeptide-PEG11-Tz was successfully radiosynthesized, with the radiochemical purity above 95%, as confirmed by reversed-phase high-performance liquid chromatography. The radioligand showed favorable stability in normal saline and phosphate-buffered saline, good affinity to RAW264.7 cells, and rapid blood clearance in mice. The results of biodistribution and imaging experiments using the pretargeted method showed that the tumor/muscle ratios were 5.17 ± 2.98, 5.94 ± 1.46, and 4.46 ± 2.73 at the pretargeting intervals of 24, 48, and 72 h, respectively. The experimental results using the method of the directly labeling antibody (89Zr-DFO-anti-CD11b) showed that, despite radioactive accumulation in the tumor, there was a higher level of radioactive accumulation in normal tissues. The tumor/muscle ratios were 1.09 ± 0.67, 1.66 ± 0.95, 2.94 ± 1.24, 3.64 ± 1.21, and 3.55 ± 1.64 at 1, 24, 48, 72, and 120 h. The current research proved the value of 68Ga-NOTA-polypeptide-PEG11-Tz/anti-CD11b-TCO in the diagnosis of GC using the pretargeted strategy. Compared to 89Zr-DFO-anti-CD11b, the image contrast achieved by the pretargeted strategy was relatively improved, and the background accumulation of the probe was relatively low. These advantages can improve the diagnostic efficiency for GC and provide supporting evidence for radioimmunotherapy targeting CD11b receptors.

Image-guided combined chemo-thermal therapy assists in optimizing treatment time, enhancing therapeutic efficiency, and circumventing side effects. In the present study, we developed a chemo-photothermal theranostic platform based on polydopamine (PDA)-coated gold nanorods (GNRs). The PDA coating was thin; however, it significantly suppressed the cytotoxicity of the cetyltrimethylammonium bromide template and allowed high cisplatin loading efficiency, arginine-glycine-aspartic acid (RGD) peptide (c(RGDyC)) conjugation, and chelator-free iodine-125 labeling (RGD-125IPt-PDA@GNRs). While loaded cisplatin was released in a pH-sensitive manner, labeled 125I was outstandingly stable under biological conditions. RGD-125IPt-PDA@GNRs had a high specificity for αvβ3 integrin, and consequently, they could selectively accumulate in tumors, as revealed by single photon emission computed tomography/CT imaging, and in target tumor angiogenic vessels, as shown by high-resolution photoacoustic imaging. As RGD-125IPt-PDA@G...

Despite all the advances in multimodal imaging, it remains a significant challenge to acquire both magnetic resonance and nuclear imaging in a single dose because of the enormous difference in sensitivity. Indeed, nuclear imaging is almost 10(6)-fold more sensitive than magnetic resonance imaging (MRI); thus, repeated injections are generally required to obtain sufficient MR signals after nuclear imaging. Here, we show that strategically engineered magnetoferritin nanoprobes can image tumors with high sensitivity and specificity using SPECT and MRI in living mice after a single intravenous injection. The magnetoferritin nanoprobes composed of (125)I radionuclide-conjugated human H-ferritin iron nanocages ((125)I-M-HFn) internalize robustly into cancer cells via a novel tumor-specific HFn-TfR1 pathway. In particular, the endocytic recycling characteristic of TfR1 transporters solves the nuclear signal blocking issue caused by the high dose nanoprobes injected for MRI, thus enabling simultaneous functional and morphological tumor imaging without reliance on multi-injections.

In this work, we have developed multiple-armed DNA tetrahedral nanostructures (TDNs) for dual-modality in vivo imaging using near-infrared (NIR) fluorescence and single-photon emission computed tomography (SPECT). We found that the presence of arm strands in TDNs remarkably enhanced their in vitro stability, allowing them to stay intact for at least 12 h in serum. By using NIR fluorescence imaging, we evaluated in mice the pharmacokinetics of TDNs, which exhibited distinctly different in vivo biodistribution patterns compared with those of double-stranded (ds)DNA. We also noticed that TDNs had twofold longer circulation time in the blood system than that of dsDNA. With the use of multiple-armed TDNs, we could precisely anchor an exact number of functional groups including tumor-targeting folic acid (FA), NIR emitter Dylight 755, and radioactive isotope (99m)Tc on prescribed positions of TDNs, which showed the capability of targeted imaging ability in cancer cells. Furthermore, we realized noninvasive tumor-targeting imaging in tumor-bearing mice by using both NIR and SPECT modalities.

In this Letter, different from conventional pretargeting, an additional novel DNA polymer with multiple copies of a target was first designed to be administrated between the antitumor antibody, and the labeled effector served as an amplification pretargeting strategy. Two phosphorothioate DNA strands, a bridging and a target strand, were hybridized to form a polymer. Polymer size, as a function of molar ratios, was then monitored by size exclusion HPLC and electrophoretic mobility shift assay. Moreover, binding efficiency of polymers with the radiolabeled effector and polymer size after hybridization were measured by HPLC as well. As the polymer was expected to produce more binding sites that would be targeted by effectors, amplification pretargeting can greatly improve accumulation of effectors in tumor. This novel proof-of-concept was then well demonstrated by the in vitro test of signal amplification in antibody-binding protein L coated plate and LS174T cells. Compared to conventional pretargeting, significantly increasing radioactive signal was observed in this designed amplification pretargeting, which would serve as a useful paradigm of the potential of oligomer polymers to improve pretargeting and other related approaches.

Our objective was to compare the performance of a micro-single photon emission computed tomography (micro-SPECT) with that of a micro-positron emission tomography (microPET) in a Her2+ tumored mice using an anti-Her2 nanoparticle radiolabeled with (99m)Tc and (18)F. Camera performance was first compared using phantoms; then a tumored mouse administered the (99m)Tc-nanoparticle was imaged on a Bioscan NanoSPECT/CT, while another tumored mouse received the identical nanoparticle, labeled now with (18)F, and was imaged on a Philips Mosaic HP PET camera. The nanoparticle was radiolabeled with (99m)Tc via MAG(3) chelation and with (18)F via SFB as an intermediate. Phantom imaging showed that the resolution of the SPECT camera was clearly superior, but even with 4 heads and multipinhole collimators, detection sensitivity was 15-fold lower. Radiolabeling of the nanoparticle by chelation with (99m)Tc was considerably easier and safer than manual covalent attachment of (18)F. Both cameras provided accurate quantitation of radioactivity over a broad range. In conclusion, when deciding between (99m)Tc vs (18)F, an advantage rests with the chelation of (99m)Tc over covalent attachment of (18)F, achieved manually or otherwise, but with these small animal cameras, this choice also results in trading lower sensitivity for higher resolution.