Endocrine Abstracts

Abstract unavailable at the time of publishing...

Radiopharmaceuticals labelled with the positron emitter Gallium-68 have had an enormous impact on the diagnostic imaging of neuroendocrine tumors using somatostatin receptor ligands and in recent years on the diagnosis of prostate cancer using PSMA ligands and subsequently their application for radioendotherapy using Yttrium-90, Lutetium-177 or more recently Actinium-225. The release of the monographs for ‘Gallium-68 chloride solution for radiolabelling’ and ‘Ga...

A new radiopharmaceutical using the somatostatin analogue octreotide has been developed for use in humans. SARTATE consists of the novel bifunctional chelator, MeCOSar, conjugated to (Tyr3)-octreotate. MeCOSar is a superior chelator for copper over a wide pH range and at room temperature, which allows for SARTATE to be used as an imaging/therapy pair when radiolabelled with copper-64 and copper-67.4Cu-SARTATE was produced by radiola...

Introduction: DOTANOC is a largely used somatostatin analogue in NETs investigations. In NODAGANOC, the DOTA is replaced by NODAGA, a chelator derivative from NOTA which is the ‘gold standard’ for Ga3+ and Cu2+ chelation because it forms more stable complexes than DOTA.[1] The aim of our study is to evaluate the affinity of NODAGANOC for somatostatin receptors (sst) and to develop a 68Ga and 64Cu labelled NODAGANOC for a fu...

The common perception is that receptor targeting peptide radiopharmaceuticals of high affinity should be prepared and administered in high specific radioactivity and thus low peptide content in order to assure high contrast uptake in the target tissue. However, both pre-clinical and clinical studies have demonstrated complexity of the translation of the observations in vitro to in vivo pharmacokinetics. The investigation of the phenomenon for clinically used ...

Objectives: Radiation induces DNA double strand breaks (DSBs) that can be visualized and enumerated as microscopic γ-H2AX and 53BP1 foci. This study analysed the dose- and time-dependency of the DNA damage in blood lymphocytes in patients after a personalised high-activity 177Lu-DOTATATE treatment.Methods: We investigated multiple blood samples of three patients up to 96 h after personalised high-activity peptide receptor radionuclid...

Abstract unavailable at the time of publishing...

Background: Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy.Methods: NETTER-1 is the first phase III, randomized trial evaluating 177Lu-DOTA0-Tyr3-Octreotate (Lutathera®) in patients with progressive, somatostatin receptor positive midgut NETs. 230 patients were randomized to receive Lutathera 7.4...

A range of innovative treatment approaches present ‘difficult development situations’ for drug developers and decision makers including medicines regulators. Treatment concepts where conventional development pathways and evidence standards may be difficult to apply include some cell therapies, gene therapies, personalised treatments, personalised treatment combinations and theranostics.The recently elaborated concept of adaptive pathways (AP) m...

If you are unfortunate enough to get NETs, and with surgical options not on the table, then at least I thought I had a reasonable head start to access the only other demonstrable treatment regime…PRRT?The equation:Australian patient + Victorian patient + Under direct care of Peter Mac team + PET scans with tumours demonstrating strong take-up of GaTate = Early TreatmentInstead of a relatively short lead...

Background: 2016 marks the 20th anniversary of PRRT and may mark the year that a commercially available PRRT product is approved in the United States for the treatment of Neuroendocrine Tumors (NETs). During these 20+ years PRRT was available to many in either small institutional studies or via single center compassionate care programs. Many retrospective analysis were done on this data showing the extended progression free survival (PFS) compared to drugs approved for the tre...

Introduction: Determining the radiation dose to both the kidneys and malignant lesions from therapeutic administrations of Y-90 DOTATOC is critical for optimal management of neuroendocrine cancer patients. Here, a new dosimetric approach uses PET/CT to quantify the absolute activity of Y-90 immediately after administration to calibrate subsequent tissue clearance monitored with bremsstrahlung SPECT. The dosimetric information is used to personalize subsequent Y-90 DOTATOC dose...

Aim: It is common practice to administer peptide receptor radionuclide therapy (PRRT) at fixed injected activity (IA) per cycle. This results in highly variable radiation doses to critical organs and undertreatment of most patients. We conceived a personalized PRRT (P-PRRT) system enabling delivery of a prescribed dose to the kidney over four cycles. Our goal was to assess the potential of P-PRRT to safely increase radiation dose rate to tumors, by performing a simulation in a...

Introduction: Diagnostic imaging of neuroendocrine tumors (NETs) is the domain of somatostatin receptor (SSTR) agonists as well as FDG PET/CT in dedifferentiated tumors. SSTR also serves as target for receptor directed peptide therapy. More recently, specific ligands targeting the chemokine receptor 4 (CXCR4) were introduced potentially offering an additional theranostic option in NETs. Here we evaluated the CXCR4 expression using 68Ga-Pentixafor PET/CT in NET patie...

Background: Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis is observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed.Aims: In the present study the expression of the five somatostatin receptor (SSTR) subtypes as well as of the chemokine receptor CXCR4 and of the endothelin receptor A (ETA) was e...

Radiolabeled peptides that target with high affinity and specificity their receptors on tumor cells are being applied as nuclear tracers for both diagnostic imaging and targeted radionuclide therapy with great success. It is an extensive process to bring a newly designed radiolabelled peptide molecule from its design into the clinic however and from a vast number of newly designed and developed radiolabeled peptides only few will finally meet the conditions for clinical applic...

177Lu-labelled compounds show many advantages for dosimetry assessments due to the attractive physical properties of the isotope which comprise a clearly separated gamma peak at 208 keV and low abundance of photons which permits reliable quantitative imaging after therapy. In addition, the low range of beta particles is advantageous for radiation protection. This talk mainly focuses on dosimetry methodology which includes consideration of the number and time points ...