PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer.

The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery.

3D small-scale dosimetry and tumor control of Ac radiopharmaceuticals for prostate cancer.

Radiopharmaceutical therapy using -emitting Ac is an emerging treatment for patients with advanced metastatic cancers. Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with -sensitive detection devices can measure radioactivity distributions at 20-40 resolution, but anatomical characterization is typically limited to 2D.

Impact of Posttreatment SPECT/CT on Patient Management During Lu-PSMA-617 Radiopharmaceutical Therapy.

Lu can be imaged after administration using SPECT/CT. Most work to date has focused on using posttreatment imaging to measure normal organ and tumor dose. We aimed to assess the impact of posttreatment SPECT/CT on the management of patients undergoing Lu-prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT).

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers.

Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called "flip-flop" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed.

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes.

Protocol for producing hyperpolarized C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule C-glycerol carbonate (C-GLC), the post-dissolution reaction, and converting HP C-GLC to an injectable HP C-bicarbonate solution.

Enhanced Prostate-specific Membrane Antigen Targeting by Precision Control of DNA Scaffolded Nanoparticle Ligand Presentation.

Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects. The design of actively targeted nanoparticles requires the grafting of a ligand that specifically binds to a highly expressed receptor on the surface of the targeted cell population. Optimizing the interactions between the targeting ligand and the receptor can maximize the cellular uptake of the nanoparticles and subsequently improve their activity.

Actinium-225 targeted alpha particle therapy for prostate cancer.

Targeted alpha particle therapy (TAT) has emerged as a promising strategy for the treatment of prostate cancer (PCa). Actinium-225 (Ac), a potent alpha-emitting radionuclide, may be incorporated into targeting vectors, causing robust and in some cases sustained antitumor responses. The development of radiolabeling techniques involving EDTA, DOTA, DOTPA, and Macropa chelators has laid the groundwork for advancements in this field.

Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized.

Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with F-FDG and FAPI compounds. Patients were administered 219 ± 43 MBq of Ga-FAP-2286 and scanned after 60 min.

Peptidoglycan-Targeted [F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection.

Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([In]-WBC SPECT, [F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall.

F-FDG Dedicated Breast PET Complementary to Breast MRI for Evaluating Early Response to Neoadjuvant Chemotherapy.

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 (F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points.

A Technique to Quantify Very Low Activities in Regions of Interest With a Collimatorless Detector.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan.

Development of CD46 targeted alpha theranostics in prostate cancer using Ce/Ac-Macropa-PEG-YS5.

Ac, a long-lived α-emitter with a half-life of 9.92 days, has garnered significant attention as a therapeutic radionuclide when coupled with monoclonal antibodies and other targeting vectors. Nevertheless, its clinical utility has been hampered by potential off-target toxicity, a lack of optimized chelators for Ac, and limitations in radiolabeling methods.

CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma.

Purpose: Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [89Zr]Zr-DFO-YS5 for imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer.

Imaging the Bacterial Cell Wall Using -Acetyl Muramic Acid-Derived Positron Emission Tomography Radiotracers.

Imaging infections in patients is challenging using conventional methods, motivating the development of positron emission tomography (PET) radiotracers targeting bacteria-specific metabolic pathways. Numerous techniques have focused on the bacterial cell wall, although peptidoglycan-targeted PET tracers have been generally limited to the short-lived carbon-11 radioisotope ( = 20.4 min).

Clinically Translatable Hyperpolarized C Bicarbonate pH Imaging Method for Use in Prostate Cancer.

Solid tumors such as prostate cancer (PCa) commonly develop an acidic microenvironment with pH 6.5-7.2, owing to heterogeneous perfusion, high metabolic activity, and rapid cell proliferation.

Chemoenzymatic Syntheses of Fluorine-18-Labeled Disaccharides from [F] FDG Yield Potent Sensors of Living Bacteria .

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[F]-fluoro-d-glucose ([F]FDG), the most common tracer used in clinical imaging, to form [F]-labeled disaccharides for detecting microorganisms based on their bacteria-specific glycan incorporation.

Covalent Proteins as Targeted Radionuclide Therapies Enhance Antitumor Effects.

Molecularly targeted radionuclide therapies (TRTs) struggle with balancing efficacy and safety, as current strategies to increase tumor absorption often alter drug pharmacokinetics to prolong circulation and normal tissue irradiation. Here we report the first covalent protein TRT, which, through reacting with the target irreversibly, increases radioactive dose to the tumor without altering the drug's pharmacokinetic profile or normal tissue biodistribution. Through genetic code expansion, we engineered a latent bioreactive amino acid into a nanobody, which binds to its target protein and forms a covalent linkage via the proximity-enabled reactivity, cross-linking the target irreversibly , on cancer cells, and on tumors .

Chemoenzymatic syntheses of fluorine-18-labeled disaccharides from [ F]FDG yield potent sensors of living bacteria .

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach, that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[ F]-fluoro-D-glucose ([ F]FDG), the most common tracer used in clinical imaging, to form [ F]-labeled disaccharides for detecting microorganisms based on their bacteria-specific glycan incorporation.

PSMA-Targeted Nanotheranostics for Imaging and Radiotherapy of Prostate Cancer.

Targeted nanotheranostic systems offer significant benefits due to the integration of diagnostic and therapeutic functionality, promoting personalized medicine. In recent years, prostate-specific membrane antigen (PSMA) has emerged as an ideal theranostic target, fueling multiple new drug approvals and changing the standard of care in prostate cancer (PCa). PSMA-targeted nanosystems such as self-assembled nanoparticles (NPs), liposomal structures, water-soluble polymers, dendrimers, and other macromolecules are under development for PCa theranostics due to their multifunctional sensing and therapeutic capabilities.

Evaluation of Ce/La as a PET Imaging Theranostic Pair for Ac α-Radiotherapeutics.

Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator Ce/La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides Ac and Th.

Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

Purpose: Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody.