Targeted Therapies in Cancer: Radionuclides, Multi-Omics and Nanomedicine

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 6242

Special Issue Editor

Special Issue Information

Dear Colleagues,

Theragnostics utilizes the same active pharmaceutical in patient selection in both in vivo diagnosis and in active therapy. This is an essential part of precision oncology, which identifies new forms of cancer and guides individual treatments. Multiomics approaches include the use of genomics, transcriptomics, proteomics, metabolomics, epigenomics, and phenomics data to explore the complexity of a disease-associated biological network, to predict prognostic biomarkers, and to identify new targeted drugs for individual cancer patients. In this Special Issue, targeted radionuclide therapies will specifically be reviewed and new original research in this field will be presented. Similarly, new target selection in diseases without current effective management is warranted. Multidisciplinary approaches with multifunctional targeted nanomedicines combine carriers with active pharmaceuticals. These transport the drug to the target tissue and can release the payload in a controlled manner. Thus, nanomedicines that penetrate deep in cancer tissue and target specific cells have been adapted in clinical trials. All research within the abovementioned topics is welcome.

You may choose our Joint Special Issue in International Journal of Molecular Sciences.

Dr. Kalevi Kairemo
Guest Editor

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Keywords

  • theragnostics
  • targeted drug delivery
  • nanomedicine
  • target validation
  • radionuclide therapies
  • nanoparticles
  • precision oncology
  • clinical trials

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Published Papers (2 papers)

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Research

13 pages, 2263 KiB  
Article
Long-Term Survival and Value of 18F-FDG PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with Second Peptide Receptor Radionuclide Therapy Course with 177Lu-DOTATATE
by Margarida Rodrigues, Kevin-Klaus Winkler, Hanna Svirydenka, Bernhard Nilica, Christian Uprimny and Irene Virgolini
Life 2021, 11(3), 198; https://doi.org/10.3390/life11030198 - 4 Mar 2021
Cited by 7 | Viewed by 2820
Abstract
Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to [...] Read more.
Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to evaluate the long-term survival and efficacy of a second PRRT course with 177Lu-DOTATE in patients with advanced gastroenteropancreatic (GEP) NETs. Furthermore, the value of 18F-FDG PET/CT in these patients was evaluated. 40 patients with GEP NETs who underwent two PRRT courses with 177Lu-DOTATATE and combined examinations with 68Ga-DOTA-TOC and 18F-FDG PET/CT were evaluated. After the second PRRT course, two patients (5.0%) were in partial remission, 21 patients (52.5%) in stable disease and 17 patients (42.5%) had progressive disease. The median overall survival was 122.10 months. After the second PRRT course, the median overall survival was significantly higher (p = 0.033) in the 18F-FDG-negative group compared to the 18F-FDG-positive group (145.50 versus 95.06 months, respectively). The median time to progression was 19.37 months. In conclusion, a second PRRT course with 177Lu-DOTATE is an effective treatment approach for GEP NET patients with disease progression. A change in 18F-FDG status after PRRT may predict the disease course and survival. Patients who are 18F-FDG-negative have a significantly longer overall survival than those who are 18F-FDG-positive. Full article
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11 pages, 1166 KiB  
Article
Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer—A Model Based on Clinical Example
by Eve Kelk, Priit Ruuge, Kristi Rohtla, Anne Poksi and Kalevi Kairemo
Life 2021, 11(2), 170; https://doi.org/10.3390/life11020170 - 22 Feb 2021
Cited by 6 | Viewed by 2840
Abstract
177Lu-DOTAGA-(l-y)fk(Sub-KuE) a.k.a. 177Lu-PSMA I&T is currently used for radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) in several centers in Europe. Background: Dosimetry is mandatory according to EU guidelines, although routine methods for dosimetry, i.e., absorbed radiation dose calculations for [...] Read more.
177Lu-DOTAGA-(l-y)fk(Sub-KuE) a.k.a. 177Lu-PSMA I&T is currently used for radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) in several centers in Europe. Background: Dosimetry is mandatory according to EU guidelines, although routine methods for dosimetry, i.e., absorbed radiation dose calculations for radiopharmaceuticals, are missing. Methods: We created a model of dosimetric analysis utilizing voxel-based dosimetry and intra-lesion radiomics to assess their practicality in routine dosimetry. Results: As an example for the model, our patient with mCRPC had excellent therapy response; quantitatively more than 97% of the metastatic tumor burden in local and distant lymph nodes and skeleton was destroyed by four cycles of RLT. The absorbed radiation doses in metastases decreased towards later cycles of RLT. Besides the change of prostate-specific membrane antigen (PSMA) concentration and absorbed doses in the tumor, further response to RLT could be predicted from biomarker changes, such as LDH and PSA. Conclusions: Individual dosimetry is needed to understand large variations in tumor doses and mixed responses; for that purpose, routine tools should be developed. The Dosimetry Research Tool (DRT) fluently performed automated organ delineation and absorbed radiation dose calculations in normal organs, and the results in our patient were in good concordance with the published studies on 177Lu-PSMA dosimetry. At the same time, we experienced considerable challenges in voxel-based dosimetry of tumor lesions. Measurements of 177Lu-PSMA activity concentrations instead of absorbed radiation dose calculations could make routine dosimetry more flexible. The first cycle of RLT seems to have quantitatively the biggest impact on the therapy effect. Radiomics analyses could probably aid in the treatment optimization, but it should be tested in large patient populations. Full article
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