Search

The combination of two imaging probes on the same biomolecule gives access to targeted bimodal imaging agents that can provide more accurate diagnosis, complementary information, or that may be used in different applications, such as nuclear imaging and fluorescence guided surgery. In this study, we demonstrate that dichlorotetrazine, a small, commercially available compound, can be used as a modular platform to easily assemble various imaging probes. Doubly labeled tetrazines can then be conjugated to a protein through a biorthogonal IEDDA reaction. A series of difunctionalized tetrazine compounds containing various chelating agents and fluorescent dyes was synthesized. As a proof of concept, one of these bimodal probes was conjugated to trastuzumab, previously modified with a constrained alkyne group, and the resulting dual-labeled antibody was evaluated in a mouse model, bearing a HER2-positive tumor. A significant uptake into tumor tissues was observed in vivo, by both SPECT-CT and fluorescence imaging, and confirmed ex vivo in biodistribution studies.

Background: Debio 1143, a potent orally available SMAC mimetic, targets inhibitors of apoptosis proteins (IAPs) members and is currently in clinical trials. In this study, nuclear imaging evaluated the effects of Debio 1143 on tumor cell death and metabolism in a triple-negative breast cancer (TNBC) cell line (MDA-MB-231)-based animal model., Methods: Apoptosis induced by Debio 1143 was assessed by FACS (caspase-3, annexin 5 (A5)), binding of 99m Tc-HYNIC-Annexin V, and a cell proliferation assay. 99m Tc-HYNIC-Annexin V SPECT and [ 18 F]-FDG PET were also performed in mice xenografted with MDA-MB-231 cells., Results: Debio 1143 induced early apoptosis both in vitro and in vivo 6 h after treatment. Debio 1143 inhibited tumor growth, which was associated with a decreased tumor [ 18 F]-FDG uptake when measured during treatment., Conclusions: This imaging study combining SPECT and PET showed the early proapoptotic effects of Debio 1143 resulting in a robust antitumor activity in a preclinical TNBC model. These imaging biomarkers represent valuable noninvasive tools for translational and clinical research in TNBC.

Multimodal nanoprobes are highly demanded for biomedical imaging applications to enhance the reliability of the diagnostic results. Among different types of nano-objects, ultrasmall silica gadolinium nanoparticle (SiGdNP) appears as a safe, effective, and versatile platform for this purpose. In this study, a new method to functionalize SiGdNP based on silane chemistry has been reported. Two types of chelating silanes (APTES-DOTAGA and APTES-NODAGA) have been synthesized and grafted on SiGdNP by a simple one-step protocol. This functionalization strategy requires no other reactants or catalyzers and does not compromise the ultrasmall size of the particles. NODAGA-functionalized particle has been labeled with 64 Cu isotope and injected intravenously to mice bearing TS/A carcinoma tumor for biodistribution study to demonstrate its potential as a bimodal MRI/PET imaging agent. A fully integrated MRI/PET system was used to simultaneously monitor the distribution of the particle. The results showed that the functionalized particle maintained properties of a renal clearable NP which could rapidly escape through kidneys and had low retention in other organs, especially liver, even though its accumulation in the tumor was modest.

We evaluated the performance characteristics of a prototype preclinical PET scanner available as an easy clippable assembly that can dock to an MRI system. The single ring version of the PET system consists of eight detectors, each of which comprises a 12  ×  12 silicon photomultipliers (SiPMs) array coupled with a dual layer of offset scintillation crystals to measure depth of interaction. The crystal arrays have 29  ×  29 (30  ×  30 for the outer layer) 4 mm long LYSO crystals (6 mm for the outer layer). The ring diameter is 119.2 mm and the axial field of view is 50.4 mm. The NEMA NU 4-2008 protocol was followed for studying the PET performance. Temperature stability of SiPMs was also investigated. The peak system absolute sensitivity was 4.70% with an energy window of 250-750 keV. The spatial resolution was 1.28/1.88/1.85 mm FWHM (radial/tangential/axial) at a distance of 5 mm from the center. Peak noise equivalent counting rate and scatter fraction for mouse phantom were 61.9 kcps at 14.9 MBq and 21.0%, respectively. The uniformity was 6.3% and the spill-over ratios in the images of the water-and air-filled chambers were 0.07 and 0.17, respectively. Recovery coefficients ranged from 0.13 to 0.96. Change in sensitivity as a function of ambient temperature was 0.3%/°C. These first results indicate excellent spatial resolution performance for use with animal studies. Moreover, the clippable assembly can be upgraded to accept a second ring of SiPMs modules, leading to improved sensitivity and axial coverage.

Unlabelled: The purpose of this study was to prospectively evaluate the relationship between tumor blood flow and glucose metabolism as evaluated by dynamic first-pass (18)F-FDG PET and by proliferation and endothelial pathologic markers in the setting of newly diagnosed breast cancer., Methods: Forty patients were prospectively included. Biopsy samples of each tumor were used to assess the Ki67 index of proliferation and immunostaining for CD34 (a panendothelial cell marker) and CD105 (a proliferation-related endothelial cell marker). All patients underwent (18)F-FDG PET/CT at least 1 wk after sample biopsy and before any treatment. A dynamic 2-min acquisition was performed immediately after intravenous injection of a 5 MBq/kg dose of (18)F-FDG; tumor blood flow was then calculated using a single-compartment kinetic model. A static acquisition was performed 90 min after injection for quantification of delayed (18)F-FDG tumor uptake (standardized uptake value maximal index [SUV(max)]), reflecting tumor metabolism., Results: Pathologic and PET/CT data were available for all patients. The SUV(max) measured on delayed PET images correlated strongly and positively with the expression of Ki67 (r = +0.69; P < 0.0001). In contrast, there was no significant correlation between SUV(max) and endothelial markers (CD34 and CD105). Tumor blood flow correlated positively with the expression of CD34 and CD105 (P = 0.016 and P = 0.007, respectively) and with the expression of Ki67 (P = 0.028). By logistic regression analysis, only expression of Ki67 remained an independent predictor of high (supramedian) SUV(max); CD105 score and histopathologic grade 3 were independently associated with a high (supramedian) tumor blood flow level., Conclusion: Tumor blood flow quantified by dynamic first-pass (18)F-FDG PET/CT is significantly associated with tumor angiogenesis as evaluated by immunohistochemistry in the setting of breast cancer, whereas tumor metabolism appears to be more associated with markers of proliferation. Thus, determination of tumor blood flow and metabolism with a single injection of (18)F-FDG could be an exciting alternative to more complex and less available techniques.