Theranostic prostate

Rationale: 225 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 225 Ac, and limitations in radiolabeling methods. In a prior study evaluating the effectiveness of CD46-targeted radioimmunotherapy, we found great therapeutic efficacy but also significant toxicity at higher doses...

A comprehensive investigation of the Hg2+ coordination chemistry and 197m/g Hg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, p -SCN-Bn-DOTA and p -SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the 197m/g Hg2+ theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%-6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10-4  M)...

For the improved delivery of cancer therapeutics and imaging agents, the conjugation of cell-penetrating peptides (CPPs) increases the cellular uptake and water solubility of agents. Among the various CPPs, arginine-rich peptides have been the most widely used. Combining CPPs with enzyme-responsive peptides presents an innovative strategy to target specific intracellular enzymes in cancer cells and when combined with the appropriate click chemistry can enhance theranostic drug delivery through the formation of intracellular self-assembled nanostructures...

Breast cancer is the most common cancer in women. Although chemotherapy is still broadly used in its treatment, adverse effects remain a challenge. In this scenario, aptamers emerge as a promising alternative for theranostic applications. Studies using breast cancer cell lines provide useful information in laboratory and preclinical investigations, most of which use cell lines established from metastatic sites. However, these cell lines correspond to cell populations of the late stage of tumor progression. On the other hand, studies using breast cancer cells established from primary sites make it possible to search for new theranostic approaches in the early stages of the disease...

Estrogen receptor (ER) β and histone deacetylases (HDACs), when overexpressed, are associated closely with the occurrence and development of prostate cancer and are, therefore, considered important targets and biomarkers used in the clinical treatment of prostate cancer. The present study involved the design and synthesis of the first ERβ and HDAC dual-target near-infrared fluorescent probe with both imaging capacity and antitumor activity for prostate cancer. Both P1 and P2 probes exhibited excellent ERβ selectivity, with P1 being almost exclusively selective for ERβ compared to ERα...

BACKGROUND: The gastrin-releasing peptide receptor (GRPR) has been extensively studied as a biomolecular target for peptide-based radiotheranostics. However, the lack of metabolic stability and the rapid clearance of peptide radioligands, including radiolabeled GRPR-antagonists, often impede clinical application. Aiming at circumventing these drawbacks, we have designed three new GRPR-antagonist radioligands using [99m Tc]Tc-DB15 ([99m Tc]Tc-N4 -AMA-DIG-D Phe-Gln-Trp-Ala-Val-Sar-His-Leu-NHEt; AMA: p-aminomethylaniline; DIG: diglycolate) as a motif, due to its high GRPR-affinity and stability to neprilysin (NEP)...

PURPOSE: To assess the prognostic value of pre-treatment [68 Ga]Ga-PSMA-11 PET/CT and other baseline clinical characteristics in predicting prostate cancer (PCa) patients response to [177 Lu]Lu-PSMA (PSMA-I&T), as well as patient survival. PROCEDURES: In this retrospective study, 81 patients who received [177 Lu]Lu-PSMA-I&T between October 2018 and January 2023 were reviewed. Eligible patients had metastatic castration-resistant PCa, underwent pre-treatment [68 Ga]Ga-PSMA-11 PET/CT, and had serum prostate-specific antigen (PSA) levels available...

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment...

We report on an adrenocortical carcinoma (ACC) patient, which has exhausted previous treatment options and was scheduled for prostate-specific membrane antigen (PSMA)- and C-X-C motif chemokine receptor 4 (CXCR4)-targeted PET/CT. We identified PSMA-avid pulmonary metastases exhibiting modest radiotracer accumulation, while chemokine receptor PET/CT provided intense uptake. This dual-tracer molecular imaging approach revealed that chemokine receptor PET appears to be more suitable in patients with advanced ACC, indicating that CXCR4-directed radioligand therapy may be considered in such patients suffering from end-stage disease...

Injectable colloidal solutions of lanthanide oxides (nanoparticles between 10 and 100 nm in size) have demonstrated high biocompatibility and no toxicity when the nanoparticulate units are functionalized with specific biomolecules that molecularly target various proteins in the tumor microenvironment. Among the proteins successfully targeted by functionalized lanthanide nanoparticles are folic receptors, fibroblast activation protein (FAP), gastrin-releasing peptide receptor (GRP-R), prostate-specific membrane antigen (PSMA), and integrins associated with tumor neovasculature...

To assess the diagnostic accuracy of 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18 F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68 Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68 Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68 Ga-FAPI and 18 F-FDG PET and had adequate lesion validation for accuracy analysis...

BACKGROUND AND AIM: Prostate-specific membrane antigen (PSMA) is ubiquitously expressed in tumor-associated neovasculature and may be a potential theranostic in many solid cancers, including breast carcinoma (BC). Herein, we analyzed the presence of PSMA in BC, through qualitative and quantitative parameters on 68 Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT), across various hormonal subtypes. METHODS: This study examined 41 female patients of BC...

Lipid-shelled nanobubbles (NBs) can be visualized and activated using noninvasive ultrasound (US) stimulation, leading to significant bioeffects. Prior work demonstrates that active targeting of NBs to prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) results in enhanced cellular internalization and prolongs NB retention with persistent, cancer-cell specific acoustic activity. In this work, we hypothesized that tumor-accumulated PSMA-NBs combined with low frequency unfocused therapeutic US (TUS) will lead to selective damage and induce a specific therapeutic effect in PSMA-expressing tumors compared to PSMA-negative tumors...

BACKGROUND: The current generation of radiolabeled PSMA-targeting therapeutic agents is limited by prominent salivary gland binding, which results in dose-limiting xerostomia from radiation exposure. JB-1498 is a urea-based small molecule with a highly negatively charged linker targeting prostate specific membrane antigen (PSMA). Prior work on a similar tracer with the same negatively charged linker demonstrated low normal organ/soft tissue background uptake compared to [68 Ga]Ga-PSMA-11...

AIM: In addition to significant improvements in sensitivity and image quality, the recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has enabled dynamic whole-body imaging for the first time. We aim herein to determine an appropriate acquisition time range for static low-dose [18 F]PSMA-1007 PET imaging and to investigate the whole-body pharmacokinetics of [18 F]PSMA-1007 by dynamic PET with the LAFOV Biograph Vision Quadra PET/CT in a group of prostate cancer patients...

Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization...

BACKGROUND: Prostate cancer (PCa) remains one of the most complex tumors in men. The assessment of gene expression is expected to have a profound impact on cancer diagnosis, prognosis, and treatment decisions. The aim of this study was to determine the utility of the epithelial-mesenchymal transition (EMT) transcription factors Twist and Snai1 in the treatment of naïve prostate cancer. METHODS AND RESULTS: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt  methods for Twist and Snail gene expression...

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Spine pain is highly prevalent and costly, but evaluation with clinical features and anatomic imaging remain limited. Fat-suppressed MR imaging and molecular imaging (MI) may help identify inflammatory, lesional, and malignant causes. Numerous MI agents are available, each with advantages and disadvantages. Herein, FDG PET, prostate-specific membrane antigen (PSMA), bone radiotracers, and others are highlighted. No specific pain MI agents have been identified, but mechanisms of key agents are shown in video format, and the mechanism of PSMA as a theranostic agent is displayed...

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted PET/CT is a well-established imaging method in prostate cancer (PC) for both staging and restaging, and also for theranostic applications. An alternative imaging method is crucial for 15% PSMA-negative cases. We aimed to investigate the contribution of 68 Ga-DOTA-FAPI-04 PET/CT to PC imaging. PATIENTS AND METHODS: Thirty-six patients diagnosed with PC were included. Patients underwent both 68 Ga-PSMA PET/CT and 68 Ga-DOTA-FAPI-04 PET/CT imaging within 1 week...