Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.

Background: Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors.

First preclinical SPECT/CT imaging and biodistribution of [Er]ErCl and [Er]Er-PSMA-617.

Background: Er (t = 10.4 h, E = 47.1 keV (59.

Long-term follow-up of bulky classic Hodgkin lymphoma managed with ABVD and PET-guided RT demonstrates excellent outcomes in PET-negative cases.

The outcome of 221 patients with bulky (≥10 cm) classic Hodgkin lymphoma (cHL) treated with doxorubicin, bleomycin, vinblastine, dacarbazine and consolidative radiotherapy (RT) only in those with a positive end-of-treatment (EOT) positron emission tomography (PET) scan was evaluated. With a median follow-up of 9.6 years, 5- and 10-year progression-free survival (PFS) in EOT PET-negative cases were 94.

Synthesis and Evaluation of Ga- and Lu-Labeled [Pro]bombesin(8-14) Derivatives for Detection and Radioligand Therapy of Gastrin-Releasing Peptide Receptor-Expressing Cancer.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of cancers and represents a promising target for diagnosis and therapy. However, the extremely high accumulation in the pancreas observed for most of the clinically evaluated GRPR-targeted radiopharmaceuticals could limit their applications. In this study, we synthesized one GRPR antagonist (ProBOMB5) and two GRPR agonists (LW02056 and LW02057) by replacing the 4-thiazolidinecarboxylic acid (Thz) residue in our previously reported GRPR-targeted tracers with Pro.

Preclinical evaluation of [Ac]Ac-crown-TATE - An alpha-emitting radiopharmaceutical for neuroendocrine tumors.

Background: Targeted alpha therapy (TAT) of somatostatin receptor-2 (SSTR2) positive neuroendocrine tumors (NETs) involving Ac-225 ([Ac]Ac-DOTA-TATE) has previously demonstrated improved therapeutic efficacy over conventional beta particle-emitting peptide receptor radionuclide therapy agents. DOTA-TATE requires harsh radiolabeling conditions for chelation of [Ac]Ac, which can limit the achievable molar activities and thus therapeutic efficacy of such TAT treatments. Macropa-TATE was recently highlighted as a potential alternative to DOTA-TATE, owing to the mild radiolabeling conditions and high affinity toward [Ac]Ac; however, elevated liver and kidney uptake were noted as a major limitation and a suitable imaging radionuclide is yet to be reported, which will be required for patient dosimetry studies and assessment of therapeutic benefit.

Synthesis and Evaluation of the First Ga-Labeled -Terminal Hydroxamate-Derived Gastrin-Releasing Peptide Receptor-Targeted Tracers for Cancer Imaging with Positron Emission Tomography.

Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a -terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized -terminal hydroxamate-derived [Ga]Ga-LW02075 ([Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [Ga]Ga-LW02050 ([Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [Ga]Ga-SB3 ([Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt).

Preclinical evaluation of MC1R targeting theranostic pair [Tb]Tb-crown-αMSH and [Tb]Tb-crown-αMSH.

Background: Targeted radionuclide therapy is established as a highly effective strategy for the treatment of metastatic tumors; however, the co-development of suitable imaging companions to therapy remains significant challenge. Theranostic isotopes of terbium (Tb, Tb, Tb, Tb) have the potential to provide chemically identical radionuclidic pairs, which collectively encompass all modes of nuclear decay relevant to nuclear medicine. Herein, we report the first radiochemistry and preclinical studies involving Tb- and Tb-labeled crown-αMSH, a small peptide-based bioconjugate suitable for targeting melanoma.

Synthesis and Evaluation of Novel Ga-Labeled [D-Phe,LeuψThz]bombesin(6-14) Analogs for Cancer Imaging with Positron Emission Tomography.

Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [Ga]Ga-TacsBOMB2 ([Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-LeuψThz-NH), which showed a minimal pancreas uptake in a preclinical mouse model.

Heterogeneous PSMA ligand uptake inside parotid glands.

Unlabelled: The purpose of this investigation is to quantify the spatial heterogeneity of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) uptake within parotid glands. We aim to quantify patterns in well-defined regions to facilitate further investigations. Furthermore, we investigate whether uptake is correlated with computed tomography (CT) texture features.

Neural blind deconvolution for deblurring and supersampling PSMA PET.

. To simultaneously deblur and supersample prostate specific membrane antigen (PSMA) positron emission tomography (PET) images using neural blind deconvolution..

Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training.

Synthesis and Preclinical Evaluation of Two Novel Ga-Labeled Bispecific PSMA/FAP-Targeted Tracers with 2-Nal-Containing PSMA-Targeted Pharmacophore and Pyridine-Based FAP-Targeted Pharmacophore.

Some bispecific radiotracers have been developed to overcome the limitations of monospecific tracers and improve detection sensitivity for heterogeneous tumor lesions. Here, we aim to synthesize two bispecific tracers targeting prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are key markers expressed in prostate cancer. A pyridine-based FAP-targeted ligand was synthesized through multi-step organic synthesis and then connected to the 2-Nal-containing PSMA-targeted motif.

Exploration of commercial cyclen-based chelators for mercury-197 m/g incorporation into theranostic radiopharmaceuticals.

A comprehensive investigation of the Hg coordination chemistry and Hg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, -SCN-Bn-DOTA and -SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the Hg 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 M). In contrast, -SCN-Bn-TCMC and -SCN-Bn-DOTA demonstrated significantly higher Hg radiochemical yields (100% ± 0.

Development, preclinical evaluation and preliminary dosimetry profiling of SB03178, a first-of-its-kind benzo[h]quinoline-based fibroblast activation protein-α-targeted radiotheranostic for cancer imaging and therapy.

Fibroblast activation protein-α (FAP) is a marker of cancer-associated fibroblasts (CAFs) that constitute a significant portion of most carcinomas. Since it plays a critical role in tumor growth and metastasis, its timely detection to identify tumor lesions in early developmental stages using targeted radiopharmaceuticals has gained significant impetus. In the present work, two novel FAP-targeted precursors SB03178 and SB04033 comprising of an atypical benzo[h]quinoline construct were synthesized and either chelated to diagnostic radionuclide gallium-68 or therapeutic radionuclide lutetium-177, with ≥90% radiochemical purities and 22-76% decay-corrected radiochemical yields.

Development of the quantitative PET prostate phantom (Q3P) for improved quality assurance of F-PSMA PET imaging in metastatic prostate cancer.

Background: Phantoms are commonly used to evaluate and compare the performance of imaging systems given the known ground truth. Positron emission tomography (PET) scanners are routinely validated using the NEMA image quality phantom, in which lesions are modeled using 10 to 37 mm fillable spheres. The NEMA phantom neglects, however, to model focal (3-10-mm), high-uptake lesions that are increasingly observed in prostate-specific membrane antigen (PSMA) PET images.

5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II.

With peptides increasingly favored as drugs, natural product motifs, namely the tryptathionine staple, found in amatoxins and phallotoxins, and the 2,2'-bis-indole found in staurosporine represent unexplored staples for unnatural peptide macrocycles. We disclose the efficient condensation of a 5-hydroxypyrroloindoline with either a cysteine-thiol or a tryptophan-indole to form a tryptathionine or 2-2'-bis-indole staple. Judicious use of protecting groups provides for chemoselective stapling using α-MSH, which provides a basis for investigating both chemoselectivity and affinity.

PSMA PET/CT as a predictive tool for subregional importance estimates in the parotid gland.

. Xerostomia and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the heterogeneity of the dose response within parotid glands. Prostate Specific Membrane Antigen (PSMA) ligands have demonstrated high uptake in salivary glands, which has been shown to correlate with gland functionality.

Toward tryptathionine-stapled one-bead-one-compound (OBOC) libraries: solid phase synthesis of a bioactive octretoate analog.

New somatostatin analogs are highly desirable for diagnosing and treating neuroendocrine tumors (NETs). Here we describe the solid-phase synthesis of a new octreotate (TATE) analog where the disulfide bond is replaced with a tryptathionine (Ttn) staple as part of an effort to prototyping a one-bead-one-compound (OBOC) library of Ttn-stapled peptides. Library design provides the potential for on- and off-bead screening.

Rearmed Bifunctional Chelating Ligand for Ac/Tb Precision-Guided Theranostic Radiopharmaceuticals─HnoneunpaX.

Superior bifunctional chelating ligands, which can sequester both α-emitting radionuclides (Ac, Bi) and their diagnostic companions (Tb, In), remain a formidable challenge to translating targeted alpha therapy, with complementary diagnostic imaging, to the clinic. HnoneupaX, a chelating ligand with an unusual diametrically opposed arrangement of pendant donor groups, has been developed to this end. HnoneunpaX preferentially complexes Ln and An ions, forming thermodynamically stable (pLa = 17.

Accuracy in Polyp Size Measurement Among Surgeons, Gastroenterologists, Trainees, and Experts: A Prospective Video-Based Study.

Introduction: Polyp size determination plays an important role in endoscopic decision making and follow-up determination. However, there is a lack of knowledge of endoscopist accuracy for polyp sizing and efficacy of available tools for size measurement. Our aim was to compare the accuracy of visual assessment, snare, forceps, and virtual scale endoscope (VSE) in estimating polyp size among a diverse group of endoscopists.