scholarly journals Update on Preclinical Development and Clinical Translation of Cholecystokinin-2 Receptor Targeting Radiopharmaceuticals

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5776
Author(s):  
Elisabeth von Guggenberg ◽  
Petra Kolenc ◽  
Christof Rottenburger ◽  
Renata Mikołajczak ◽  
Alicja Hubalewska-Dydejczyk
Keyword(s):  
Clinical Trials ◽  
Radionuclide Therapy ◽  
Medullary Thyroid Cancer ◽  
Clinical Results ◽  
Targeted Imaging ◽  
Clinical Use ◽  
Targeted Radionuclide Therapy ◽  
Imaging Studies ◽  
Preclinical Development ◽  
Medullary Thyroid

The cholecystokinin-2 receptor (CCK2R) has been a target of interest for molecular imaging and targeted radionuclide therapy for two decades. However, so far CCK2R targeted imaging and therapy has not been introduced in clinical practice. Within this review the recent radiopharmaceutical development of CCK2R targeting compounds and the ongoing clinical trials are presented. Currently, new gastrin derivatives as well as nonpeptidic substances are being developed to improve the properties for clinical use. A team of specialists from the field of radiopharmacy and nuclear medicine reviewed the available literature and summarized their own experiences in the development and clinical testing of CCK2R targeting radiopharmaceuticals. The recent clinical trials with novel radiolabeled minigastrin analogs demonstrate the potential for both applications, imaging as well as targeted radiotherapy, and reinforce the clinical applicability within a theranostic concept. The intense efforts in optimizing CCK2R targeting radiopharmaceuticals has led to new substances for clinical use, as shown in first imaging studies in patients with advanced medullary thyroid cancer. The first clinical results suggest that the wider clinical implication of CCK2R-targeted radiopharmaceuticals is reasonable.

Radiolanthanides in endoradiotherapy: an overview

2007 ◽  
Vol 95 (6) ◽  
Author(s):  
Frank Rösch
Keyword(s):  
Radionuclide Therapy ◽  
Molecular Level ◽  
Interdisciplinary Approach ◽  
Clinical Use ◽  
Targeted Radionuclide Therapy ◽  
Nuclear Decay ◽  
Decay Products ◽  
Disease Site ◽  
Decay Parameters ◽  
Targeting Vector

Endoradiotherapy (targeted radionuclide therapy) is a systemic approach, involving a radiolabeled targeting vector with a well characterized biochemical strategy to selectively deliver a cytotoxic level of radiation to a disease site on a cellular/molecular level. The group of radiolanthanides has been considered both for imaging and therapy over many years. Some radiolanthanides have been and are increasingly applied for therapeutic purposes.However, the clinical use of endoradiotherapeuticals containing radiolanthanides requires a complex and interdisciplinary approach. It involves, among other factors, the choice of the most suitable lanthanide radionuclide (in terms of nuclear decay parameters such as type and energy of the particles emitted, half-life, decay products

External Beam and Nuclear Therapy of Medullary Thyroid Cancer

2021 ◽  
Vol 66 (1) ◽  
pp. 79-84
Author(s):  
I Pimonova ◽  
V. Krylov ◽  
P Isaev ◽  
T. Kochetova ◽  
E Borodavina
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Radionuclide Therapy ◽  
Medullary Thyroid Cancer ◽  
Combined Therapy ◽  
Somatostatin Analogs ◽  
Distant Metastases ◽  
Targeted Drugs ◽  
Medullary Thyroid ◽  
Peptide Receptor

The article reviews domestic and foreign literature on the use of radiation therapy in the treatment of medullary thyroid cancer. The possibilities of various radiation methods in the treatment of patients with distant metastases are shown. In addition to classical types of remote irradiation, data are presented on the possibilities of radionuclide therapy (peptide-receptor therapy with somatostatin analogs and radionuclide therapy with osteotropic drugs for bone metastases). Methods of combined therapy with the use of osteomodifying agents, targeted drugs and other methods are described, which make it possible to increase the effectiveness of treatment of patients with medullary thyroid cancer with bone metastases.

scholarly journals Comparison of 68Ga PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases

2018 ◽  
Vol 103 (9) ◽  
pp. 3250-3259 ◽  
Author(s):  
Luciana Audi Castroneves ◽  
George Coura Filho ◽  
Ricardo Miguel Costa de Freitas ◽  
Raphael Salles ◽  
Raquel Ajub Moyses ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Medullary Thyroid Cancer ◽  
Imaging Studies ◽  
Medullary Thyroid ◽  
Pet Ct

scholarly journals Clinical trials in molecular radiotherapy—Tribulations and Triumphs Report of the NCRI CTRad meeting held at the Lift Islington, 8 June 2018

2019 ◽  
Vol 92 (1100) ◽  
pp. 20190117 ◽  
Author(s):  
Nadia Falzone ◽  
Rebecca Gregory ◽  
Matthew Aldridge ◽  
Samantha YA Terry ◽  
Glenn Flux
Keyword(s):  
Clinical Trials ◽  
Nuclear Medicine ◽  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy ◽  
Molecular Radiotherapy ◽  
Challenges And Opportunities ◽  
The Uk

It has been almost a decade since the commentary Molecular radiotherapy — the radionuclide raffle? by Gaze and Flux (2010). The overarching feeling then was that no individual or organisation has taken up the challenge, nationally or internationally, of championing molecular targeted radionuclide therapy in all its aspects. Here, we report on the recent NCRI–CTRad (Clinical Trials in Molecular Radiotherapy–Tribulations and Triumphs) meeting, held in London on the 8 June 2018. The meeting was organized by the NCRI–CTRad to review the challenges and opportunities for clinical trials in molecular radiotherapy, particularly focussing on investigator-led trials that incorporate imaging and dosimetry, and to discuss how the community can move forward. This meeting was organised in conjunction with the British Nuclear Medicine Society and reflects the progress of Nuclear Medicine in the UK.

Is There a Role for Peptide Receptor Radionuclide Therapy in Medullary Thyroid Cancer?

2015 ◽  
Vol 40 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Fernanda Vaisman ◽  
Paulo Henrique Rosado de Castro ◽  
Flavia Paiva Proença Lobo Lopes ◽  
Daniel Barretto Kendler ◽  
Cencita H.N. Pessoa ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Radionuclide Therapy ◽  
Medullary Thyroid Cancer ◽  
Peptide Receptor Radionuclide Therapy ◽  
Medullary Thyroid ◽  
Peptide Receptor

scholarly journals Efficacy of vandetanib in the treatment of medullary thyroid cancer: literature review and case report

2019 ◽  
Vol 9 (3) ◽  
pp. 38-48
Author(s):  
А. М. Mudunov ◽  
Yu. V. Alymov ◽  
I. S. Romanov ◽  
S. О. Podvyaznikov ◽  
А. V. Ignatova
Keyword(s):  
Clinical Trials ◽  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Medullary Thyroid Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Individual Characteristics ◽  
Medullary Thyroid ◽  
Mechanisms Of Carcinogenesis ◽  
Thyroid Malignancies

Medullary thyroid cancer (MTC) is a rare disorder that accounts for approximately 1.7 % of all thyroid malignancies. MTC is usually detected at early stages; however, approximately 10–15 % of patients are diagnosed with locally advanced MTC and distant metastases. Treatment of such patients is challenging due to biological characteristics of the disease and very few effective treatment approaches available. The investigation of mechanisms of carcinogenesis, as well as advances in pharmacology, allowed the development of a new group of targeted drugs, namely tyrosine kinases, which efficacy against progressive unresectable locally advanced or metastatic MTC has been demonstrated in multiple clinical trials. Vandetanib has been registered for MTC treatment in the Russian Federation. MTC is very rare, thus, each case of vandetanib use for its treatment is particularly interesting. Moreover, since the approval of this drug in 2011 by the U. S. Food and Drug Administration (FDA), new data on the clinical use of vandetanib have been accumulated. Importantly, clinical trials are usually well designed and conducted in near-ideal conditions, whereas the real conditions can be different and patients may have individual characteristics. Therefore, the aim of this study was to update the information on the efficacy and safety of vandetanib by retrospective analysis of available publications and to report a case of MTC treated with vandetanib.

The Role of Radionuclide Therapy in Medullary Thyroid Cancer

2003 ◽  
Vol 89 (5) ◽  
pp. 560-562 ◽  
Author(s):  
Maria Rita Castellani ◽  
Alessandra Alessi ◽  
Giordano Savelli ◽  
Emilio Bombardieri
Keyword(s):  
Thyroid Cancer ◽  
Radionuclide Therapy ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

Improved detection of medullary thyroid cancer with radiolabeled antibodies to carcinoembryonic antigen.

1996 ◽  
Vol 14 (4) ◽  
pp. 1209-1217 ◽  
Author(s):  
M Juweid ◽  
R M Sharkey ◽  
T Behr ◽  
L C Swayne ◽  
A D Rubin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Carcinoembryonic Antigen ◽  
Medullary Thyroid Cancer ◽  
Imaging Studies ◽  
Medullary Thyroid ◽  
Primary Surgery ◽  
Occult Disease ◽  
Iodine 131 ◽  
Iodine 123 ◽  
Magnetic Resonance Imaging Mri

PURPOSE This investigation was undertaken to assess the targeting of established and occult medullary thyroid cancer (MTC) with radiolabeled monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). PATIENTS AND METHODS Twenty-six assessable patients with known (n = 17) or occult (n = 9) MTC were studied with radiolabeled anti-CEA MAbs. Scintigraphic images were collected to determine targeting of tumor lesions. RESULTS The targeting results of technetium 99m (99mTc)-,iodine 123 (123I)-, and iodine 131 (131I)-labeled anti-CEA antibodies (all directed against the same epitope of CEA) indicated that all these reagents were capable of detecting established and occult MTC. The sensitivity for detection of known sites of disease ranged from 76% to 100% for the various anti-CEA MAbs used, when compared with computed tomography (CT), magnetic resonance imaging (MRI), bone scan, or other imaging modalities. Moreover, the antibody scan was positive in seven of nine patients with occult disease (patients with negative conventional imaging studies, but who had elevated calcitonin and/or CEA levels). Three of seven patients underwent surgery and the disease was confirmed by histopathology in all three. CONCLUSION Anti-CEA MAbs are excellent agents for imaging recurrent, residual, or metastatic MTC. The high lesion sensitivity in patients with known lesions, combined with the ability to detect disease, may make these agents ideal for staging patients, monitoring disease pretherapy or posttherapy, and especially for evaluating patients with recurrent or persistent hypercalcitonemia or CEA elevations after primary surgery. Analogous to radioiodine in the evaluation of patients with differentiated thyroid cancer, radiolabeled anti-CEA MAbs may achieve a similar role in diagnosing and monitoring patients with MTC.

scholarly journals Advances in the Management of Medullary Thyroid Carcinoma: Focus on Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 9 (11) ◽  
pp. 3507
Author(s):  
Erika Grossrubatscher ◽  
Giuseppe Fanciulli ◽  
Luca Pes ◽  
Franz Sesti ◽  
Carlotta Dolci ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Radionuclide Therapy ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Peptide Receptor Radionuclide Therapy ◽  
Neuroendocrine Neoplasms ◽  
Medullary Thyroid ◽  
Peptide Receptor

Effective treatment options in advanced/progressive/metastatic medullary thyroid carcinoma (MTC) are currently limited. As in other neuroendocrine neoplasms (NENs), peptide receptor radionuclide therapy (PRRT) has been used as a therapeutic option in MTC. To date, however, there are no published reviews dealing with PRRT approaches. We performed an in-depth narrative review on the studies published in this field and collected information on registered clinical trials related to this topic. We identified 19 published studies, collectively involving more than 200 patients with MTC, and four registered clinical trials. Most cases of MTC were treated with PRRT with somatostatin analogues (SSAs) radiolabelled with 90 yttrium (90Y) and 177 lutetium (177Lu). These radiopharmaceuticals show efficacy in the treatment of patients with MTC, with a favourable radiological response (stable disease, partial response or complete response) in more than 60% of cases, coupled with low toxicity. As MTC specifically also expresses cholecystokinin receptors (CCK2Rs), PRRT with this target has also been tried, and some randomised trials are ongoing. Overall, PRRT seems to have an effective role and might be considered in the therapeutic strategy of advanced/progressive/metastatic MTC.

scholarly journals New drugs for medullary thyroid cancer: new promises?

2016 ◽  
Vol 23 (6) ◽  
pp. R287-R297 ◽  
Author(s):  
Christine Spitzweg ◽  
John C Morris ◽  
Keith C Bible
Keyword(s):  
Clinical Trials ◽  
Thyroid Cancer ◽  
Complex Disease ◽  
Medullary Thyroid Cancer ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Genetic Alterations ◽  
New Drugs ◽  
Targeted Agents ◽  
Medullary Thyroid

Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives.

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