Novel Multifunctional NIR-II Aggregation-Induced Emission Nanoparticles Assisted Intraoperative Identification and Elimination of Residual Tumor

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

GdxFe3-xO4 nanoparticles with silane shell as potential theranostic agent for cancer treatment

In this study of GdxFe3-xO4 compound core silane shell nanoparticles method is represented.Samples were analyzed with SEM, EDA and FTIR spectroscopy. Further attaching of carborane compounds is discussed. Products can be used in biomedical applications for MRI imaging and drug delivery for NCT, so can be considered as potential theranostic agents for cancer treatment.

MOLECULAR DOCKING AND ADMET PREDICTION OF 5-BENZYLOXYTRYPTOPHAN AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER

Objective: This in silico study aims to determine the inhibition effect of 5-BOTP with various bifunctional chelating agents (BFCA); NOTA, DOTA, TETA, CTPA, H2CB-DO2A, H2CBTE2A against the antiporter site of the LAT1. Methods: The research method consisted of the binding mode of 5-BOTP and its derivatives with LAT1, the docking score, the analysis of preADMET, and the overview of Ro5 compatibility. Results: The results showed that 5-BOTP-NOTA and 5-BOTP-DOTA had interactions with the gating residue (Phe252, Trp257, Asn258, and Tyr259) on the antiporter site of LAT1. 5-BOTP-NOTA and 5-BOTP-DOTA affinity are around-11.50 and-9.14 kcal/mol, respectively. Conclusion: Based on this study, 5-BOTP-NOTA and 5-BOTP-DOTA are the new compounds that have the potential as a theranostic agent of cancer by inhibiting LAT1.

Feasibility Study of Copper-64 Radioisotope Production by Secondary Fast Neutron Bombardment

As a beta and positron emitter, copper-64 (Cu-64) has been coined a theranostic agent in nuclear medicine. Copper-64 is generally produced by bombarding a nickel-64 target with a proton beam via 64Ni(p,n)64Cu nuclear reaction. In this work, secondary fast neutrons are proposed to produce Cu-64 radioisotope via 64Zn(n,p)64Cu nuclear reaction. The secondary fast neutrons were produced by a 10 MeV proton-irradiated primary titanium (Ti) target simulated using the PHITS 3.16 code. In the simulation, the Ti target thickness was varied from 0.01 to 0.1 cm to obtain the optimum secondary fast neutron flux, which was calculated in the rear, radial, and front directions. The Cu-64 radioactivity yield was then computed using the TENDL 2019 nuclear cross-section data. Also, the expected radioactive impurities during Cu-64 production were predicted. The simulation results indicated that the total fast neutron flux resulted from the 10-MeV proton bombarded Be target was 1.70x1012 n/cm2s. The maximum integrated Cu-64 radioactivity yield was 2.33 MBq/µAh when 0.03 cm thick Ti target was shot with 10-MeV protons. The most significant impurities predicted during the bombardment were radioactive isotopes e.g., Co-61, and Zn-65, with the total radioactivity yield estimated to be 0.28 Bq/µAh.

Radiotheranostic Agents Targeting Neuroblastoma: State-of-the-Art and Emerging Perspectives

Neuroblastoma (NB) represents the most common extracranial tumor of childhood. Prognosis is quite variable, ranging from spontaneous regression to aggressive behavior with wide metastatization, high mortality, and limited therapeutic options. Radiotheranostics combines a radiopharmaceutical pair in a unique approach, suitable both for diagnosis and therapy. For many years, metaiodobenzylguanidine (MIBG), labeled with 123I for imaging or 131I for therapy, has represented the main theranostic agent in NB, since up to 90% of NB incorporates the aforementioned radiopharmaceutical. In recent years, novel theranostic agents hold promise in moving the field of NB radiotheranostics forward. In particular, SarTATE, consisting of octreotate targeting somatostatin receptors, has been applied with encouraging results, with 64Cu-SARTATE being used for disease detection and with 67Cu-SARTATE being used for therapy. Furthermore, recent evidence has highlighted the potential of targeted alpha therapy (TAT) for treating cancer by virtue of alpha particles’ high ionizing density and high probability of killing cells along their track. On this path, 211At-astatobenzylguanidine (MABG) has been developed as a potential agent for TAT and is actually under evaluation in preclinical NB models. In this review, we performed a web-based and desktop literature research concerning radiotheranostic approaches in NB, covering both the radiopharmaceuticals already implemented in clinical practice (i.e.,123/1311-MIBG) and those still in a preliminary or preclinical phase.