Molecular Imaging最新文献

Positron-emitting nuclides have long been used as imaging agents in medical science to spatially trace processes non-invasively, allowing for real-time molecular imaging using low tracer concentrations. This ability to non-destructively visualize processes in real time also makes positron imaging uniquely suitable for probing various processes in plants and porous environmental media, such as soils and sediments. Here, we provide an overview of historical and current applications of positron imaging in environmental research. We highlight plant physiological research, where positron imaging has been used extensively to image dynamics of macronutrients, signalling molecules, trace elements, and contaminant metals under various conditions and perturbations. We describe how positron imaging is used in porous soils and sediments to visualize transport, flow, and microbial metabolic processes. We also address the interface between positron imaging and other imaging approaches, and present accompanying chemical analysis of labelled compounds for reviewed topics, highlighting the bridge between positron imaging and complementary techniques across scales. Finally, we discuss possible future applications of positron imaging and its potential as a nexus of interdisciplinary biogeochemical research.

Purpose: As stereotactic radiosurgery (SRS) and immunotherapy are increasingly used to treat brain metastases, incidence of radiation necrosis (RN) is consequently rising. Differentiating tumor regrowth (TR) from RN is vital in management but difficult to assess using MRI. We hypothesized that tumor methionine levels would be elevated given increased metabolism and high amino acid uptake, whereas RN would increase inflammation marked by upregulated translocator protein (PBR-TSPO), which can be quantified with specific PET tracers.

Procedures: We performed a feasibility study to prospectively evaluate [¹¹C]methionine and [¹¹C]PBR28 using PET in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate TR from RN.

Results: Sequential imaging with dual tracers was well-tolerated. [¹¹C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [¹¹C]PBR28 was only accurate in 3/7 lesions. Tumor PBR-TSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [¹¹C]PBR28-PET.

Conclusion: Sequential use of PET tracers is safe and effective. [¹¹C]Methionine was a reliable TR marker, but [¹¹C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging.

Background: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients, using ¹⁸F-PI 2620 dynamic PET acquisition.

Methods: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic ¹⁸F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions.

Results: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of ¹⁸F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups.

Conclusion: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

This meeting report summarizes a Consultants Meeting that was held at International Atomic Energy Agency headquarters in Vienna to provide an update on radionuclide imaging for neuroscience applications.

Breast cancer continues to be the most lethal cancer type in women and one of the most diagnosed. Understanding Breast cancer receptor status is one of the most vital processes for determining treatment options. One type of breast cancer, human epidermal growth factor receptor 2 (HER2) positive, has approved receptor-based therapies including trastuzumab and pertuzumab that can significantly increase the likelihood of survival. Current methods to determine HER2 status include biopsies with immunohistochemical staining and/or fluorescence in situ hybridization. However, positron emission tomography (PET) imaging techniques using ⁸⁹Zr-trastuzumab or ⁸⁹Zr-pertuzumab are currently in clinical trials for a non-invasive, full body diagnostic approach. Although the antibodies have strong specificity to the HER2 positive lesions, challenges involving long post-injection time for imaging due to the blood circulation of the antibodies and matching of long-live isotopes leading to increased dose to the patient leave opportunities for alternative PET imaging probes. Peptides have been shown to allow for shorter injection-to-imaging time and can be used with shorter lived isotopes. HER2 specific peptides under development will help improve the diagnosis and potentially therapy options for HER2 positive breast cancer. Peptides showing specificity for HER2 could start widespread development of molecular imaging techniques for HER2 positive cancers.

Heat shock protein expression can be induced by heat shock making it possible to artificially modulate their levels noninvasively in vivo in a spatially and temporally controlled manner. Here, we report the use of the major heat shock protein 70 (HSP70) as an inducible target by using the small molecule deoxyspergualin (DSG) conjugated to the near-infrared fluorophore (Cy5.5). We demonstrate that heat induction in the form of localized hyperthermia of normal tissue in living mice results in sufficient HSP70 overexpression for detection with DSG-Cy5.5 conjugate. This effect is dependent on total energy delivered and reaches maximum fluorescence signal in 6 to 8 hours post heat induction and declines over a period of up to 24 hours. These results suggest that DSG-Cy5.5 agent accumulates in tissue with elevated HSP70 by heat.

Although, superparamagnetic iron oxide nanoparticles (SPIONs) have extensively been used as a contrasting agent for magnetic resonance imaging (MRI), the lack of intrinsic fluorescence restricted their application as a multimodal probe, especially in combination with light microscopy. In Addition, the bigger size of the particle renders them incompetent for bioimaging of small organelles. Herein, we report, not only the synthesis of ultrasmall carbon containing magneto-fluorescent SPIONs with size ∼5 nm, but also demonstrate its capability as a multicolor imaging probe. Using MCF-7 and HeLa cell lines, we show that the SPIONs can provide high contrast mulicolor images of the cytoplasm from blue to red region. Further, single particle level photon count data revealed that the SPIONs could efficaciously be utilized in localization based super resolution microscopy in future.

Asn-Gly-Arg (NGR) motifs have vasculature-homing properties via interactions with the aminopeptidase N (CD13) expressed on tumor neovasculature. Numerous NGR peptides with different molecular scaffolds have been exploited for targeted delivery of different compounds for imaging and therapy. When conjugated with NGR, complexes recognize the CD13 receptor expressed on the tumor vasculature, which improves the specificity to tumor and avoids systematic toxic reactions. Both preclinical and clinical studies performed with these products suggest that NGR-mediated vascular targeting is an effective strategy for delivering bioactive amounts of cytokines to tumor endothelial cells. For molecular imaging, radiolabeled peptides have been the most successful approach and have been translated into clinic. This review describes current data on radiolabeled tumor vasculature-homing NGR peptides for imaging and therapy.

New platforms are enabling radiochemistry to be carried out in tiny, microliter-scale volumes, and this capability has enormous benefits for the production of radiopharmaceuticals. These droplet-based technologies can achieve comparable or better yields compared to conventional methods, but with vastly reduced reagent consumption, shorter synthesis time, higher molar activity (even for low activity batches), faster purification, and ultra-compact system size. We review here the state of the art of this emerging direction, summarize the radiotracers and prosthetic groups that have been synthesized in droplet format, describe recent achievements in scaling up activity levels, and discuss advantages and limitations and the future outlook of these innovative devices.

An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [⁶⁴Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with ¹⁸F-2-fluoro-2-deoxyglucose ([¹⁸F]FDG: 10 mCi), followed by [⁶⁴Cu]-DOTA-BFab ([⁶⁴Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [¹⁸F]FDG-PET scan. 4 weeks later the patient received of [⁶⁴Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [¹⁸F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [⁶⁴Cu]BFab at 1 and 24 hours after tracer administration. The [⁶⁴Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [⁶⁴Cu]BFab-PET signals.