Pandey, Mukesh K

Abstract A low-cost, easy-to-adopt noninvasive imaging modality for differentiating bacterial infection from inflammation is desirable to accurately diagnose bacterial infections. Herein, a bacteria-specific PET probe, [68Ga]Ga-BP, was developed and evaluated in rat models of foreign body-associated osteomyelitis induced by methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae and was directly compared with sterile inflammation and uninstrumented uninfected controls. [68Ga]Ga-BP-based imaging of MRSA-infected tibiae was also compared to [68Ga]Ga-citrate and [18F]FDG. After iron depletion, dynamic PET/CT imaging was performed at 15–120 min postinjection of radiotracers, followed by assessment of ex vivo biodistribution. [68Ga]Ga-BP successfully detected tibial infection and demonstrated >6-fold higher uptake in infected tibiae with all three bacterial species versus contralateral tibiae via PET imaging. [68Ga]Ga-BP outperformed [68Ga]Ga-citrate and [18F]FDG in identifying MRSA infection. [68Ga]Ga-BP represents a promising, noninvasive PET imaging agent for direct bacterial detection and bacterial infection treatment monitoring.

The dynamic field of radiopharmaceuticals is currently experiencing an explosion of growth due in part to excitement over the emerging field of theranostics (therapy and diagnostics). Radiopharmaceuticals use physiological targeting methods to deliver radionuclides with medically relevant decay properties to disease biomarkers for diagnosis and treatment, offering opportunities for early disease imaging and radiation therapy treatment in disease pathologies that are inoperable or refractory to other forms of radiotherapy. Sustaining this rapidly growing field depends heavily on the continued design and production of novel, effective radiopharmaceuticals. Effective therapeutic radiopharmaceuticals cause complex and varied cellular responses, and to choose radionuclides that maximize therapeutic response, researchers must understand radiation biology. Cellular radiation response depends heavily on factors including linear energy transfer (LET), dose, dose rate, targeted location, direct or indirect energy deposition mechanisms, the broader cellular matrix, cellular stress signaling pathways, and endogenous radiation protection mechanisms. Because of the extensive application of low-LET external beam radiation on clinical cancer treatments, biological responses to low-LET form the basis of radiation biology and are generally considered transferable to high-LET radiopharmaceuticals. However, increased focus on high-LET, radiopharmaceutical therapy-specific radiation biology is motivated by differences between low- and high-LET radiation, external beam versus radiopharmaceutical therapy-induced biological response, and the observed varied clinical responses to radiopharmaceutical therapies. This review article summarizes historical understanding of low- and high-LET radiation responses within cells, with emphasis on radiopharmaceutical-specific responses when available, and discusses current gaps in understanding in the radiation biology of radiotheranostic pharmaceuticals.

New solvent-free polymer electrolytes are proposed based on a linear perfluorinated copolymer synthesized by enzymatic methods. The system is biphasic and exhibits two distinct conductivity pathways for long-range Na + -cation migration.

This review delves into the realm of gallium-68 ( 68 Ga)-labeled radiopharmaceuticals.

Abstract The roles of nucleoplasm-residing nucleoporins (NUP) in solid tumors, including prostate cancer, remain unknown. In this study, we reveal the clinical significance and mechanistic role of the off-pore NUP, soluble POM121 (sPOM121), as a crucial transcriptional regulator that enhances the aggressiveness of metastatic prostate cancer. Using orthogonal methodologies in human samples, sPOM121 was identified as the predominantly expressed nucleoplasmic NUP in prostate cancer. Unbiased proteomic and epigenomic studies demonstrate that sPOM121, through its C-terminus, interacts with the chromatin remodeler SMARCA5 at gene promoter sites and localizes at nuclear condensates, reprogramming gene expression. Indeed, sPOM121 regulates a distinct oncogenic gene network, including β-catenin, leading to prostate cancer progression and immune evasion. Importantly, targeting the sPOM121/β-catenin axis in patient-derived preclinical and syngeneic mouse models halts prostate cancer aggressiveness and enhances antitumor immunity. Taken together, these findings reveal previously unknown actionable reprogramming functions of off-pore NUPs in solid tumors. Significance: This study uncovers how oncogenic signaling programs are transcriptionally heightened by the NUP sPOM121 in metastatic prostate cancer. Localization of sPOM121 at active transcriptional nuclear condensates propels disease progression and immune evasion, offering novel anticancer therapeutic opportunities.

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.

The radiotracer [ 68 Ga]Ga-NOTA-CTP was evaluated in healthy and diseased CD1 mice with myocardial infarction following ligation of the left anterior descending artery.