Towards Optimal Automated Ga-Radiolabeling Conditions of the DOTA-Bisphosphonate BPAMD Without Pre-Purification of the Generator Eluate.

DOTA-functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with Ga. Moreover, the versatility of DOTA allows the complexation of radiometals with therapeutic applications (e.g.

Biophysical insights into sugar-dependent medium acidification promoting YfaL protein-mediated self-aggregation, biofilm formation and acid stress resistance.

The ability of bacteria to interact with their environment is crucial to form aggregates and biofilms, and develop a collective stress resistance behavior. Despite its environmental and medical importance, bacterial aggregation is poorly understood and mediated by few known adhesion structures. Here, we identified a new role for a surface-exposed protein, YfaL, which can self-recognize and induce bacterial autoaggregation.

New Drugs for Targeted Radionuclide Therapy in Metastatic Prostate Cancer.

Metastatic prostate cancer is a frequent and fatal disease. Targeted radionuclide therapy (TRT) has become a readily available therapeutic option since the approval of [Lu]Lu-PSMA-617. Various molecules are currently being studied for TRT in prostate cancer.

Prognostic Value of F-FDG PET/CT Assessment After Radiotherapy of Squamous Cell Carcinoma of the Anus in Patients from the National Multicentric Cohort FFCD-ANABASE.

This study aimed to evaluate the prognostic value of F-FDG PET/CT qualitative assessment in terms of recurrence-free survival (RFS), colostomy-free survival (CFS), and overall survival (OS) after radiation therapy (RT) of squamous cell carcinoma of the anus (SCCA). Secondary objectives were to evaluate the prognostic value of baseline and posttherapeutic quantitative F-FDG PET/CT parameters in terms of RFS, CFS, and OS. We included all consecutive patients from the French multicentric cohort FFCD-ANABASE who had undergone F-FDG PET/CT at baseline and 4-6 mo after RT or chemoradiotherapy for a localized SCCA.

LYMPHOSCORE (Lymphoscintigraphy Scoring Reliability) Reliability of a New Qualitative and Semiquantitative Lymphoscintigraphy Scoring System for Primary Lymphedema.

Purpose Of The Report: Primary lymphedema (PLE) is a rare chronic disorder. Extremity lymphoscintigraphy offers access for dynamic and functional information on peripheral lymphatics and lymph nodes. We aimed to assess intraobserver and interobserver reliability of a new lymphoscintigraphy quantitative and qualitative scoring system in a homogeneous population of adult patients followed for PLE of the lower limb(s).

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from Lu. The objective of this work was to explore how postinfusion [Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity.

"One Method to Label Them All": A Single Fully Automated Protocol for GMP-Compliant Ga Radiolabeling of PSMA-11, Transposable to PSMA-I&T and PSMA-617.

Background: Prostate-specific membrane antigen (PSMA) is an ideal target for molecular imaging and targeted radionuclide therapy in prostate cancer. Consequently, various PSMA ligands were developed. Some of these molecules are functionalized with a chelator that can host radiometals, such as Ga for PET imaging.

[Ga]Ga-FAPI-46 synthesis on a GAIA® module system: Thorough study of the automated radiolabeling reaction conditions.

The influence of several parameters involved in the Ga radiolabeling of FAPI-46 was studied at the scale of the automated reaction. Among the buffers tested, HEPES 0.3 M pH 4 allowed both high radiochemical purity (RCP) and radiochemical yield (RCY), without prepurification of Ga but after final purification of [Ga]Ga-FAPI-46 on a C cartridge.

Bisphosphonates as Radiopharmaceuticals: Spotlight on the Development and Clinical Use of DOTAZOL in Diagnostics and Palliative Radionuclide Therapy.

Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as Tc-radiolabelled oxidronate and medronate remain first-line bone scintigraphic imaging agents for both oncology and non-oncology indications. In line with the growing interest in theranostic molecules, bifunctional bisphosphonates bearing a chelating moiety capable of complexing a variety of radiometals were designed.

GRECCAR 14 - a multicentric, randomized, phase II-III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol.

Aim: Total neoadjuvant treatment (TNT) is becoming standard in patients with locally advanced rectal carcinoma (LARC). Preoperative chemoradiotherapy (CRT) has proven side effects on bowel and genitourinary function. An early tumoral response to induction chemotherapy demonstrates its high prognostic value.

Fc-engineered monoclonal antibodies to reduce off-target liver uptake.

Background: Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; FcγR).

Identification of F-FDG PET/CT Parameters Associated with Weight Loss in Patients with Esophageal Cancer.

F-FDG PET-CT is routinely performed as part of the initial staging of numerous cancers. Other than having descriptive, predictive and prognostic values for tumors, F-FDG PET-CT provides full-body data, which could inform on concurrent pathophysiological processes such as malnutrition. To test this hypothesis, we measured the F-FDG uptake in several organs and evaluated their association with weight loss in patients at diagnosis of esophageal cancer.

Immunomodulatory effects of targeted radionuclide therapy.

It is now clear that conventional radiation therapy can reinstate cell death immunogenicity. Recent preclinical data indicate that targeted radionuclide therapy that irradiate tumors at continuous low dose rate also can elicit immunostimulatory effects and represents a promising strategy to circumvent immune checkpoint inhibitor resistance. In this perspective, we discuss the accumulating preclinical and clinical data suggesting that activation of the immune system through the cGAS-STING axis and the release of extracellular vesicles by irradiated cells, participate to this antitumor immunity.

Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices.

Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years.

Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera) Case.

Background And Objective: Lu-177 DOTATATE (Lutathera) is a radiolabeled analog of somatostatin administered intravenously in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Biodistribution of Lu-177 DOTATATE in tumor and healthy tissues can be monitored by serial post-injection scintigraphy imaging. Patient exposure to the drug is variable with the recommended fixed dosage, and hence there is a variable response to treatment.

Ac-Labeled Somatostatin Analogs in the Management of Neuroendocrine Tumors: From Radiochemistry to Clinic.

The widespread use of peptide receptor radionuclide therapy (PRRT) represents a major therapeutic breakthrough in nuclear medicine, particularly since the introduction of Lu-radiolabeled somatostatin analogs. These radiopharmaceuticals have especially improved progression-free survival and quality of life in patients with inoperable metastatic gastroenteropancreatic neuroendocrine tumors expressing somatostatin receptors. In the case of aggressive or resistant disease, the use of somatostatin derivatives radiolabeled with an alpha-emitter could provide a promising alternative.

Prevention of post-hepatectomy liver failure after major resection of colorectal liver metastases: is hepato-biliary scintigraphy the optimal tool?

Background: Liver failure is the most threatening complication after hepatectomy for colorectal liver metastases. Recent studies indicate that liver functional evaluation by hepatobiliary scintigraphy (HBS) could be more sensitive than volumetry to predict the risk of post-hepatectomy liver failure (PHLF). The aim of this study was to evaluate the performance of Tc-mebrofenin HBS, when used as the main preoperative assessment before major hepatectomy in patients with liver metastases from colorectal cancer.

A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera® in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH).

Background: Although neuroendocrine tumors (NET) are classed as rare, they have a high prevalence and their incidence is increasing. Effective treatment with lutetium -[177Lu]Lu-oxodotreotide (Lutathera®) is possible in patients with well-differentiated NET, improving progression-free survival (PFS), overall survival (OS), and quality of life (QoL). However, progression does occur.

Development and Implementation of a Professional Practices Evaluation during Radiopharmaceuticals Administration.

Securing both the patient and radiopharmaceuticals (RPs) circuit is an essential concern in nuclear medicine (NM). These circuits converge at the RP administration phase, a key step in patient management in NM. In a continuous quality improvement approach, we developed and implemented an evaluation of professional practices (EPPs) methodology focused on RPs injection to identify and correct deviations from good practices.

Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods.

Objectives: Lu-oxodotreotide (Lutathera) is an intravenous peptide receptor radionuclide therapy to treat unresectable metastatic digestive neuroendocrine tumours. The recommended method for Lutathera administration is gravity infusion; however, other appropriate and safe techniques are possible. This work compares two infusion methods from a medico-economic, radiation protection, efficiency and practicality point of view.

Unusual Focal Lung Uptake without CT Abnormality on a Bone Scan: What Might It Mean?

A 48-year-old woman was referred for a bone scan as an assessment of bone metastasis from breast cancer. Surprisingly, two hot spots of lung uptake were present in the left lung without any abnormality on CT slices. No history of pulmonary disease was observed.

AAZTA-Derived Chelators for the Design of Innovative Radiopharmaceuticals with Theranostic Applications.

With the development of Ga and Lu radiochemistry, theranostic approaches in modern nuclear medicine enabling patient-centered personalized medicine applications have been growing in the last decade. In conjunction with the search for new relevant molecular targets, the design of innovative chelating agents to easily form stable complexes with various radiometals for theranostic applications has gained evident momentum. Initially conceived for magnetic resonance imaging applications, the chelating agent AAZTA features a mesocyclic seven-membered diazepane ring, conferring some of the properties of both acyclic and macrocyclic chelating agents.

Myocardial perfusion quantification with Rb-82 PET: good interobserver agreement of Carimas software on global, regional, and segmental levels.

Purpose: To estimate the interobserver agreement of the Carimas software package (SP) on global, regional, and segmental levels for the most widely used myocardial perfusion PET tracer-Rb-82.

Materials And Methods: Rest and stress Rb-82 PET scans of 48 patients with suspected or known coronary artery disease (CAD) were analyzed in four centers using the Carimas SP. We considered values to agree if they simultaneously had an intraclass correlation coefficient (ICC) > 0.

Tailored Media-Fill Test Protocols Inspired by Ga Kit-Based Radiopharmaceuticals.

Gallium-68 radiolabeling is an increasingly common activity in radiopharmacy. Single vial cold kits to radiolabel DOTATOC and PSMA-11 with Ga were developed, either for manual or automated preparation. Both approaches are very specific and require aseptic compounding skills, raising the need for dedicated training.