Comparative analysis of positron emitters for theranostic applications based on small bioconjugates highlighting Sc, Cu and Ti.

Background: Targeted radionuclide therapy with Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with Ga, offering good imaging up to ≈2 h post-injection. However, the optimal tumor-to-background ratio is often reached later.

Rational design of NT-PSMA heterobivalent probes for prostate cancer theranostics.

Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions.

Palladium-103 (Pd/Rh), a promising Auger-electron emitter for targeted radionuclide therapy of disseminated tumor cells - absorbed doses in single cells and clusters, with comparison to Lu and Tb.

Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of Pd (T = 16.

Development of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode.

The neuropeptide-Y (NPY) family acts through four G protein-coupled receptor subtypes in humans, namely, Y, Y, Y, and Y. A growing body of evidence suggest the involvement of the NPY system in several cancers, notably the Y subtype, thus acting as a relevant target for the development of radiopharmaceuticals for imaging or targeted radionuclide therapy (TRT). Here, the [cPP(1-7),NPY(19-23),Ala,Aib,Gln]hPP scaffold, further referred to as sYago, was modified with a DOTA chelator and radiolabeled with Ga and In and investigated and using the MCF-7 model.

Membrane and Nuclear Absorbed Doses from Lu and Tb in Tumor Clusters: Effect of Cellular Heterogeneity and Potential Benefit of Dual Targeting-A Monte Carlo Study.

Early use of targeted radionuclide therapy to eradicate tumor cell clusters and micrometastases might offer cure. However, there is a need to select appropriate radionuclides and assess the potential impact of heterogeneous targeting. The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from Lu and Tb (β-emitter with additional conversion and Auger electrons) in a cluster of 19 cells (14-μm diameter, 10-μm nucleus).

Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers.

Bivalent ligands, i.e., molecules having two ligands covalently connected by a linker, have been gathering attention since the first description of their pharmacological potential in the early 80s.

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

Unlabelled: The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal.

Methods: First, we prospectively performed neurotensin receptor-1 (NTS) IHC in a series of patients receiving both [Ga]Ga-PSMA-617 and [Ga]Ga-RM2 before prostatectomy.

Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ.

Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2.

Neurotensin receptor 2 (NTS) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS.

Comparison of Ga-PSMA-617 PET/CT and Ga-RM2 PET/CT in Patients with Localized Prostate Cancer Who Are Candidates for Radical Prostatectomy: A Prospective, Single-Arm, Single-Center, Phase II Study.

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making.

Expression of neurotensin receptor-1 (NTS) in primary breast tumors, cellular distribution, and association with clinical and biological factors.

Purpose: Neurotensin receptor-1 (NTS) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS expression have not been fully clarified.

Methods: We studied NTS expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS expression and clinical, pathological, and biological parameters, as well as patient outcomes.

Ga-Radiolabeling and Pharmacological Characterization of a Kit-Based Formulation of the Gastrin-Releasing Peptide Receptor (GRP-R) Antagonist RM2 for Convenient Preparation of [Ga]Ga-RM2.

Background: [Ga]Ga-RM2 is a potent Gastrin-Releasing Peptide-receptor (GRP-R) antagonist for imaging prostate cancer and breast cancer, currently under clinical evaluation in several specialized centers around the world. Targeted radionuclide therapy of GRP-R-expressing tumors is also being investigated. We here report the characteristics of a kit-based formulation of RM2 that should ease the development of GRP-R imaging and make it available to more institutions and patients.

Silicon-Containing Neurotensin Analogues as Radiopharmaceuticals for NTS-Positive Tumors Imaging.

Several independent studies have demonstrated the overexpression of NTS in various malignancies, which make this receptor of interest for imaging and therapy. To date, radiolabeled neurotensin analogues suffer from low plasmatic stability and thus insufficient availability for high uptake in tumors. We report the development of Ga-radiolabeled neurotensin analogues with improved radiopharmaceutical properties through the introduction of the silicon-containing amino acid trimethylsilylalanine (TMSAla).

Radiation doses from Tb and Lu in single tumour cells and micrometastases.

Background: Targeted radionuclide therapy (TRT) is gaining importance. For TRT to be also used as adjuvant therapy or for treating minimal residual disease, there is a need to increase the radiation dose to small tumours. The aim of this in silico study was to compare the performances of Tb (a medium-energy β emitter with additional Auger and conversion electron emissions) and Lu for irradiating single tumour cells and micrometastases, with various distributions of the radionuclide.

Design, synthesis, and biological evaluation of a multifunctional neuropeptide-Y conjugate for selective nuclear delivery of radiolanthanides.

Background: Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA.

68Ga-PSMA-617 Compared With 68Ga-RM2 and 18F-FCholine PET/CT for the Initial Staging of High-Risk Prostate Cancer.

Ga-labeled prostate-specific membrane antigen inhibitors and Ga-labeled gastrin-releasing peptide receptor antagonists showed interesting results for staging biochemically recurrent prostate cancer. In this case, Ga-prostate-specific membrane antigen-617 PET/CT, Ga-RM2 PET/CT, and F-choline PET/CT were performed in a patient (66-year-old man, prostate-specific antigen = 6.7 ng/mL) with biopsy-proven Gleason 9 (5 + 4) prostate cancer, candidate for radical prostatectomy and lymph node dissection.

Comparison of the radiolabeled PSMA-inhibitor In-PSMA-617 and the radiolabeled GRP-R antagonist In-RM2 in primary prostate cancer samples.

Purpose: Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer.

Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases.

Neurotensin and its high-affinity receptor, NTR₁, are involved in the growth of various tumors. Few data are available regarding NTR₁ expression in normal and tumoral human prostate tissue samples. NTR₁ expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available).

Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression.