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Zaknun J.J.,International Atomic Energy Agency | Zaknun J.J.,Center for Molecular Radiotherapy and Molecular Imaging | Bodei L.,Italian National Cancer Institute | Mueller-Brand J.,University of Basel | And 6 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours. PRRNT employing the radiotagged somatostatin receptor agonists 90Y-DOTATOC ([90Y-DOTA0,Tyr 3]-octreotide) or 177Lu-DOTATATE ([177Lu- DOTA0,Tyr3,Thr8]-octreotide or [ 177Lu-DOTA0,Tyr3]-octreotate) have been successfully used for the past 15 years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving 177Lu-DOTATATE or 90Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations. This guidance was formulated based on recent literature and leading experts' opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency. © 2013 Springer-Verlag Berlin Heidelberg.

Bodei L.,Italian National Cancer Institute | Bodei L.,Yale University | Kidd M.,Yale University | Baum R.P.,Center for Molecular Radiotherapy and Molecular Imaging | Modlin I.M.,Yale University
Journal of Nuclear Medicine | Year: 2014

Peptide receptor radionuclide therapy is a treatment for inoperable or metastatic neuroendocrine tumors. A key issue is the need to standardize the treatment and develop randomized controlled trials. Standardization would help define the characteristics of response, including progressionfree survival; provide homogeneous phase II and III studies; delineate the position of peptide receptor radionuclide therapy in the therapeutic algorithm for neuroendocrine tumors; and establish the basis for approval by the regulatory authorities. Standardization of treatments is the starting point to redefine the treatment paradigm from a one-size-fits-all to a personalized treatment. To delineate the treatment paradigm, treatments should be optimized for efficacy and minimization of long-term toxicity, through dosimetry, and adapted to each individual, including relevant patient characteristics. Although differences in therapy outcomes may be explained by the specific absorbed dose (or biologically effective dose), they may also be related to discrete tumor- and patient-specific features. In this respect, a particular area of investigation is the assessment of genetic elements regulating tumor cell proliferation, especially those involved in the response to cytotoxic therapies. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Grabowski P.,Charite - Medical University of Berlin | Briest F.,Charite - Medical University of Berlin | Briest F.,Free University of Berlin | Baum R.P.,Center for Molecular Radiotherapy and Molecular Imaging | And 3 more authors.
Drugs of Today | Year: 2012

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Kulkarni H.R.,Center for Molecular Radiotherapy and Molecular Imaging | Baum R.P.,Center for Molecular Radiotherapy and Molecular Imaging
PET Clinics | Year: 2014

Neuroendocrine tumors are malignant solid tumors originating from neuroendocrine cells dispersed throughout the body. Differentiated neuroendocrine tumors overexpress somatostatin receptors (SSTRs), which enable the diagnosis using radiolabeled somatostatin analogues. Internalization and retention within the tumor cell are important for peptide receptor radionuclide therapy using the same peptide. The use of the same DOTA-peptide for SSTR PET/CT using 68Ga and for peptide receptor radionuclide therapy using therapeutic radionuclides like 177Lu and 90Y offers a unique theranostic advantage. © 2014 Elsevier Inc.

Kulkarni H.R.,Center for Molecular Radiotherapy and Molecular Imaging | Baum R.P.,Center for Molecular Radiotherapy and Molecular Imaging
PET Clinics | Year: 2014

Peptide receptor radionuclide therapy involves selective targeting of neuroendocrine tumors through the somatostatin receptors, the aim being to increase radiation dose to the tumors and spare the normal tissue. The advantage of this internal radiation therapy is the ability to selectively target multiple metastases throughout the body. Early and accurate assessment of therapy response helps not only to identify the poor responders but also to personalize the treatment regimes with the aim of achieving maximum treatment benefit. This is the basis of theranostics. © 2014 Elsevier Inc.

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