Advances in Peptide Receptor Radionuclide Therapy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Radiopharmaceutical Sciences".

Deadline for manuscript submissions: closed (25 March 2022) | Viewed by 9636

Special Issue Editor


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Guest Editor
Department of Radiology, Marienhospital Bonn, 53127 Bonn, Germany
Interests: neuroendocrine tumours; PRRT in NET; nuclear oncology; nuclear medicine; medical imaging

Special Issue Information

Dear Colleagues,

In recent years, peptide receptor radionuclide therapy (PRRT) has gained increasing interest since the NETTER-1 Phase III trial showed that patients with midgut neuroendocrine tumors (NETs) achieved better outcomes with PRRT compared to a group treated with a somatostatin receptor analog: longer progression-free survival (p < 0.001), better overall response and, presumably, better overall survival (median not reached; p = 0.004). Currently, a large randomized multicenter study, the COMPETE trial, is exploring the survival of patients with gastro-entero-pancreatic NETs after PRRT compared to treatment with everolimus (ClinicalTrials.gov Identifier: NCT03049189). There are also currently several approaches to increasing the effectiveness of PRRT, for example, alpha-targeted treatment instead of PRRT with beta particles, antagonists SSTR-targeting instead of agonists, intra-arterial PRRT instead of intravenous application and PRRT combined with other therapies. Furthermore, the targeting of somatostatin receptors can also be applied for some disorders and tumors other than NETs, such as thyroid cancer, refractory meningioma and sarcoidosis. In this special issue of Pharmaceuticals, we would like to present articles focusing on current promising modifications of PRRT for the therapy of NETs, recent reports from prospective trials, novel combination therapies and examples of PRRT applications for non-NET diseases.

Dr. Anna Yordanova
Guest Editor

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Keywords

  • PRRT
  • prospective trails
  • phase III
  • alpha therapy
  • intra-arterial PRRT
  • combined PRRT
  • NET
  • non-NET

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Published Papers (3 papers)

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Research

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7 pages, 497 KiB  
Communication
Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE
by Amir Sabet, Nicolai Mader, Jörg Thomas Bittenbring, Fadi Khreish, Frank Grünwald, Hans Jürgen Biersack and Samer Ezziddin
Pharmaceuticals 2021, 14(10), 1022; https://doi.org/10.3390/ph14101022 - 5 Oct 2021
Cited by 2 | Viewed by 1871
Abstract
Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we [...] Read more.
Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity. Full article
(This article belongs to the Special Issue Advances in Peptide Receptor Radionuclide Therapy)
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Review

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13 pages, 1135 KiB  
Review
Combination Therapies with PRRT
by Anna Yordanova and Hojjat Ahmadzadehfar
Pharmaceuticals 2021, 14(10), 1005; https://doi.org/10.3390/ph14101005 - 30 Sep 2021
Cited by 10 | Viewed by 3711
Abstract
Peptide receptor radionuclide therapy (PRRT) is a successful targeted radionuclide therapy in neuroendocrine tumors (NETs). However, complete responses remain elusive. Combined treatments anticipate synergistic effects and thus better responses by combining ionizing radiation with other anti-tumor treatments. Furthermore, multimodal therapies often have a [...] Read more.
Peptide receptor radionuclide therapy (PRRT) is a successful targeted radionuclide therapy in neuroendocrine tumors (NETs). However, complete responses remain elusive. Combined treatments anticipate synergistic effects and thus better responses by combining ionizing radiation with other anti-tumor treatments. Furthermore, multimodal therapies often have a balanced toxicity profile. To date, few studies have evaluated the effect of combination therapies with PRRT, some of them phase I/II trials. This review will focus on several clinically tested, tailored approaches to improving the effects of PRRT. The aim is to help clinicians in the treatment planning of NETs to choose the most effective and safe treatment for each patient in the sense of personalized medicine. Current promising combination partners of PRRT are somatostatin analogues (SSAs), chemotherapy, molecular targeted treatment, liver radioembolization, and dual radionuclide PRRT (Lutetium-177-PRRT combined with Yttrium-90-PRRT). Full article
(This article belongs to the Special Issue Advances in Peptide Receptor Radionuclide Therapy)
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16 pages, 1210 KiB  
Review
Peptide Receptor Radionuclide Therapy and Primary Brain Tumors: An Overview
by Andrea Cimini, Maria Ricci, Francesca Russo, Martina Egidi, Ferdinando Calabria, Antonio Bagnato, Orazio Schillaci and Agostino Chiaravalloti
Pharmaceuticals 2021, 14(9), 872; https://doi.org/10.3390/ph14090872 - 29 Aug 2021
Cited by 9 | Viewed by 3188
Abstract
Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or [...] Read more.
Primary brain tumors (PBTs) are some of the most difficult types of cancer to treat, and despite advancements in surgery, chemotherapy and radiotherapy, new strategies for the treatment of PBTs are needed, especially for those with poor prognosis such as inoperable/difficult-to-reach lesions or relapsing disease. In regard to the last point, malignant primary brain tumors remain some of the most lethal types of cancer. Nuclear medicine may provide exciting new weapons and significant contributions in the treatment of PBTs. In this review, we performed literature research in order to highlight the possible role of peptide receptor radionuclide therapy (PRRT) in the treatment of PBTs with radiolabeled molecules that bind with high-affinity transmembrane receptors such as somatostatin receptors (SSTRs), neurokinin type-1 receptor and prostate-specific membrane antigen (PSMA). These receptors are overexpressed in some cancer types such as gliomas, meningiomas, pituitary tumors and medulloblastomas. A comprehensive overview of possible applications in this field will be shown, providing knowledge about benefits, feasibility, developments and limitations of PRRT in this type of tumor, also revealing new advantages in the management of the disease. Full article
(This article belongs to the Special Issue Advances in Peptide Receptor Radionuclide Therapy)
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