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Dosimetry Applied to Peptide Radionuclide Receptor Therapy
Published in Marco Chinol, Giovanni Paganelli, Radionuclide Peptide Cancer Therapy, 2016
The interrelated aspects of molecular biology, radiochemistry, nuclear medicine, and radiobiology have played an essential role in the evolution of new radiolabeled molecules for the diagnosis and therapy of positive somatostatin receptor tumors. The experience acquired in the diagnosis of neuroendocrine tumors represented the basis for the development of peptide radionuclide receptor therapy (PRRT), with a constantly increasing spectrum of applications. The clinical trials carried out over the last few years represented not only a promising new option in the management of patients with inoperable or metastasized neuroendocrine tumors but also a source of essential data for further PRRT developments. In such challenging perspectives, the efforts of dosimetrists have been focused on providing useful information for treatment planning and toxicity prevention. Many important results have been obtained, but many new or unsolved problems still require solution, with the final aim of finding a dose–effect relationship.
Breast Imaging with Radiolabeled Peptides
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Eric P. Krenning, Marion de Jong, Roelf Valkema, Casper H.J. van Eijck
It is clear from the above-mentioned information that radiolabeled peptides are new radioligands for scintigraphy of breast cancer. In the opinion of the authors, their future application in breast cancer scintigraphy has to be aimed at their in vivo use as prognostic predictors and not necessarily for localization per se, since other powerful alternatives are already available in nuclear medicine. An exception might be the demonstration or localization of the presence of recurrence of breast cancer, since up to now it is questionable whether sensitive technique(s) exist(s) to show the recurrence of disease in an early phase [99,100]. Somatostatin receptor scintigraphy might be an exception for this objective [77; see above]. Also, peptide receptor radionuclide therapy using radionuclides with appropriate particle ranges may become an new treatment modality. One might consider the use of radiolabeled somatostatin analogs first in an adjuvant setting after surgery of somatostatin receptor-positive primary breast cancer to eradicate occult metastases and, second, for breast cancer recurrence at a later stage. Studies with the aim to find compounds which upregulate in vivo the density of somatostatin receptors on tumors were not successful up to now. Thus, the only way to obtain the highest accumulation of a radiolabeled somatostatin analog in a tumor is by selecting an analog showing the highest binding and a concomitant appropriate biodistribution. New developments in this area, especially for somatostatin analogs, have been mentioned here. Also, the use of radiosensitizers may enhance the radiobiologic effect of peptide receptor radionuclide therapy.
Non-Obstructing Small Bowel Neuroendocrine Tumor with Liver Metastasis
Published in Savio George Barreto, Shailesh V. Shrikhande, Dilemmas in Abdominal Surgery, 2020
Mufaddal Kazi, Manish S. Bhandare, Vikram A. Chaudhari, Shailesh V. Shrikhande
In the case discussed above, surgery for the primary bowel lesion was not offered to begin with because of absence of symptoms such as pain, obstruction, or bleeding. After complete evaluation, the diagnosis of grade 1, functional small bowel neuroendocrine tumor with liver-limited metastasis (bilobar unresectable) was made. Since somatostatin receptor expression was present, long-acting release octreotide was offered as first-line treatment for control of symptoms as well a disease burden. For achieving downsizing and offering a possible future curative resection (for small bowel as well as liver), transarterial embolization of right lobe lesions was also performed. For control of liver disease, options range from resection, cytoreduction, ablation, and transarterial therapies besides octreotide and peptide receptor radionuclide therapy. The choice is based on the possibility of achieving R0 resection with surgery with anatomical and size criteria. Subsequently, peptide receptor radionuclide therapy was offered in view of disease progression. Although peptide receptor radionuclide therapy was also an option in the beginning, considering the dramatic responses and upcoming evidence in favor of the same, the exact sequence of peptide receptor radionuclide therapy and long-acting release somatostatin analogues is still uncertain. As of today, peptide receptor radionuclide therapy can be used as reserve therapy in refractory disease as well as first-line therapy in cases with high disease burden. Later, small bowel surgery had to be performed in emergency as he developed symptoms of obstruction, which he tolerated well. He went on to complete the planned peptide receptor radionuclide therapy and finally as there was a complete response in left lobe liver lesions, making it a right limited liver disease, liver resection (right hepatectomy) is planned with curative intent.
Myelosuppression in patients treated with 177Lutetium-lilotomab satetraxetan can be predicted with absorbed dose to the red marrow as the only variable
Published in Acta Oncologica, 2021
Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Anne Catrine Martinsen, Arne Kolstad, Caroline Stokke
Absorbed dose to red marrow enabled identification of high-risk patients for myelotoxicity after therapy with [177Lu]Lu-lilotomab satetraxetan as it could be calculated as early as 7 days post-treatment, before the onset of neutropenia and thrombocytopenia. Severe myelosuppression was uncommon for our patient group [25] who received a single dose of radioimmunotherapy. However, the prediction of hematologic toxicity might become particularly interesting for repeated administrations. Dosimetry after the first treatment cycle can then, in a multi-cycle treatment protocol, be used to predict the toxicity of future cycles, and thus be used to tailor the number and size of the cycles. Such an approach has been explored in peptide receptor radionuclide therapy [38]. Results in a murine model have suggested that fractionated therapy is a possible treatment strategy for [177Lu]Lu-lilotomab satetraxetan [39]. In such a treatment setting, patients could benefit from being stratified into groups that can allow for more intensive treatment for those that have a more favorable therapeutic index.
Theranostic approaches in nuclear medicine: current status and future prospects
Published in Expert Review of Medical Devices, 2020
Luca Filippi, Agostino Chiaravalloti, Orazio Schillaci, Roberto Cianni, Oreste Bagni
In the panorama of personalized medicine, the theranostic approach aims to identify specific targets in patients in order to define customized pathways of therapy and also monitor the response to treatment. Targeted therapy represents a crucial role for the management of neuroendocrine tumors (NET) through the peptide receptor radionuclide therapy (PRRT) [7]. Furthermore, theranostics is providing promising results in patients affected by metastatic castration-resistant prostate cancer (mCRPC) [8]. In the following, we will review the more consolidated applications of targeted imaging and therapy in nuclear medicine, also providing an overview of the more innovative applications that are moving the theranostic field forward. Table 1 summarizes the main manuscripts on the clinical application of theranostics.
Hepatic micrometastases outside macrometastases are present in all patients with ileal neuroendocrine primary tumour at the time of liver resection
Published in Scandinavian Journal of Gastroenterology, 2019
Reidar Fossmark, Tine M. Balto, Tom C. Martinsen, Jon E. Grønbech, Bjørn Munkvold, Patricia G. Mjønes, Helge L. Waldum
Several non-surgical treatment modalities improve the overall prognosis of patients with metastatic SI-NET, as well as of patients with disease recurrence after surgery. Somatostatin analogues are the mainstay of SI-NET treatment and have anti-tumour as well as symptom-reducing effects and prolong progression-free survival [12,13]. In addition, Peptide Receptor Radionuclide Therapy (PRRT) increases progression free survival rates and may also increase overall survival [14,15]. Therapy directed against focal liver metastases, such as embolisation or radiofrequency ablation of liver metastases, also has a role in selected patients [4,16]. Considering the mentioned treatment modalities, the rationale for surgical resection of SI-NET liver metastasis could be re-evaluated if it was demonstrated that most patients have multiple hepatic micrometastases at the time of liver resection.