Effectiveness and Safety of Retreatment with Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of Lu-DOTATATE therapy in patients with progressive NETs.

Peptide Receptor Radionuclide Therapy in Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma is a rare, aggressive skin malignancy, also known as neuroendocrine carcinoma of the skin, with high rates of recurrence and distant metastasis. In refractory metastatic Merkel cell carcinoma (mMCC), besides immunotherapy, chemotherapy, and radiation, peptide receptor radionuclide therapy (PRRT) may be a viable option since this type of tumor can express somatostatin receptors. We performed a comprehensive review of the literature to evaluate the efficacy of PRRT in mMCC patients.

Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [Cu]Cu-DOTA-TOC.

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging.

Targeted -Emitter Therapy with Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial.

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the β-particle emitter Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy.

Safety of PSMA-Targeted Molecular Radioligand Therapy with Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312).

The purpose of this analysis was to report the safety evaluation of Lu-PSMA-617 derived from the cohort of 64 patients exposed to Lu-PSMA-617 in the RESIST-PC trial NCT03042312 RESIST-PC was a prospective multicenter phase 2 trial. Patients with progressive metastatic castration-resistant prostate cancer after ≥ 1 novel androgen-axis drug, either chemotherapy naïve or postchemotherapy, with sufficient bone marrow reserve, normal kidney function, sufficient PSMA expression by PSMA PET, and no PSMA-negative soft-tissue lesions were eligible. Patients were randomized (1:1) into 2 activity groups (6.

Nomograms to predict outcomes after Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study.

Background: Lutetium-177 (Lu) prostate-specific membrane antigen (Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after Lu-PSMA in patients with mCRPC.

Tumor Sink Effect in Ga-PSMA-11 PET: Myth or Reality?

We aimed to systematically determine the impact of tumor burden on Ga-prostate-specific membrane antigen-11 (Ga-PSMA) PET biodistribution by the use of quantitative measurements. This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm), low (quintile 2, 25-189 cm), moderate (quintile 3, 189-532 cm), high (quintile 4, 532-1,355 cm), or very high (quintile 5, ≥1,355 cm) total PSMA-positive tumor volume (PSMA-VOL).

Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with Lu-PSMA-617 for metastatic castration-reSISTant Prostate Cancer (RESIST-PC): efficacy results of the UCLA cohort.

The objective of this study was to determine prospectively the efficacy profile of 2 activity regimens of Lu-PSMA therapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC): 6.0 vs. 7.

Peptide receptor radionuclide therapy for treatment of metastatic neuroendocrine tumors in children.

Neuroendocrine tumors (NETs) of the pancreas and midgut are extremely rare in children, and patients presenting with metastatic disease have poor survival. Given this rarity, treatments are extrapolated from guidelines for adults with NET. Recent clinical trials in adults with NETs have shown that the addition of peptide receptor radionuclide therapy (PRRT) with Lu-DOTATATE resulted in a disease control rate of nearly 80%, with minimal side effects.

Efficacy and Safety of Lu-labeled Prostate-specific Membrane Antigen Radionuclide Treatment in Patients with Diffuse Bone Marrow Involvement: A Multicenter Retrospective Study.

The Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a "superscan" by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography.

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-Dotatate: an analysis of the NETTER-1 study.

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-Dotatate.

Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS).

Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First U.S. Prospective, Reader-Masked Clinical Trial.

Studies demonstrate that the investigational Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of Cu-DOTATATE that facilitates diagnostic-quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. A dose-ranging study was conducted on 12 patients divided into 3 dose groups (111 MBq [3.

Preclinical Investigation of Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model.

Somatostatin analogues have been examined as a treatment for somatostatin receptor overexpressing tumors for years; specifically, octreotate (TATE) and octreotide (TOC). Several versions of these analogues coupled to beta or gamma nuclides are currently used as imaging agents, as treatments with peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumors or are being explored in preclinical and clinical settings. Our study describes the use of Pb-DOTAMTATE, the octreotate analogue, in combination with Pb, the parent of an alpha emitter.

Safety and Effectiveness of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy After Regional Hepatic Embolization in Patients With Somatostatin-Expressing Neuroendocrine Tumors.

Purpose: Peptide receptor radionuclide therapy (PRRT) with Lu-DOTATATE is shown to be an effective therapeutic option for somatostatin-expressing neuroendocrine neoplasms. Some concerns are raised over safety of this modality in patients with a history of regional chemoembolization and radionuclide hepatic embolization (CRHE) and is cause of reluctance among some physicians for suggesting Lu-DOTATATE in this patient population.

Methods: We retrospectively reviewed 143 patients with somatostatin-expressing neuroendocrine tumors who underwent Lu-DOTATATE PRRT.

Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment.

Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium Lu, we now present further results of Lu DOTATATE therapy in managing NETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group.

Patients And Methods: One hundred forty-four consecutive patients (85 men and 59 women; age range, 11-87 years; mean age, 58.

Phase 3 Trial of Lu-Dotatate for Midgut Neuroendocrine Tumors.

Background: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors.

Methods: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-Dotatate (116 patients) at a dose of 7.

Radiosynthesis of clinical doses of ⁶⁸Ga-DOTATATE (GalioMedix™) and validation of organic-matrix-based ⁶⁸Ge/⁶⁸Ga generators.

Introduction: 68Ga-DOTATATE is a radiolabeled peptide-based agonist that targets somatostatin receptors overexpressed in neuroendocrine tumors. Here, we present our results on validation of organic matrix 68Ge/68Ga generators (ITG GmbH) applied for radiosynthesis of the clinical doses of 68Ga-DOTATATE (GalioMedixTM).

Methods: The clinical grade of DOTATATE (25 μg±5 μg) compounded in 1 M NaOAc at pH=5.

Assessment of vulnerable atherosclerotic and fibrotic plaques in coronary arteries using (68)Ga-DOTATATE PET/CT.

Activated macrophages which express somatostatin receptor-2 (SSTR-2) play a vital role in rupture of the vulnerable atherosclerotic plaques, which result in death. (68)Ga-DOTATATE binds to somatostatin receptors 2, and therefore, can serve as potential radiotracer to detect atherosclerotic plaques. The purpose of this study was to generate preliminary data with this agent in vulnerable or fibrotic atherosclerotic plaques in the coronary arteries.

The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature.

Neuroendocrine tumors (NETs) are rare group of neoplasms arising from nervous and endocrine systems. Somatostatin analogue imaging is a functional imaging modality of choice for evaluating the NETs. Recent availability of positron emitting radioisotope labeled somatostatin analogues to image neuroendocrine cancers, has raised the interests to use this new imaging modality in management of patients with NETs.

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience.

Objective: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs.

Methods: Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonrandomized, phase 2 clinical trial.

Pictorial review of SPECT/CT imaging applications in clinical nuclear medicine.

Integrated SPECT/CT scanners are gaining popularity as hybrid molecular imaging devices which can acquire SPECT and CT in a single exam. CT can be a low dose non-contrast enhanced scan for attenuation correction and anatomical localization, or a contrast enhanced diagnostic quality scan for additional anatomical characterization. We present a pictorial review highlighting the usefulness of this emerging technology.

Long-Term Survival, Toxicity Profile, and role of F-18 FDG PET/CT scan in Patients with Progressive Neuroendocrine Tumors Following Peptide Receptor Radionuclide Therapy with High Activity In-111 Pentetreotide.

Aim: To study the long term benefits, toxicity and survival rate in patients with neuroendocrine tumors receiving multiple cycles of high activity In-111 Pentetreotide therapy. Moreover, our secondary aim was to evaluate the value of F-18 FDG PET-CT scan as prognostic indicator in this group of patients.

Background: Neuroendocrine tumors are a heterogeneous group of malignancies which are usually metastatic at diagnosis.