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Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development...
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Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development (Volume II)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 5645

Special Issue Editors

Prof. Dr. Vladimir Tolmachev

E-Mail Website
Guest Editor
Department of Immunology, Genetics and Pathology (IGP), Dag Hammarskjölds väg 20 Uppsala University, SE-751 85 Uppsala, Sweden
Interests: radionuclide; targeting; imaging; therapy; scaffold proteins; antibody; peptide; pretargeting
Special Issues, Collections and Topics in MDPI journals
Dr. Anzhelika Vorobyeva

E-Mail Website
Guest Editor
Department of Immunology, Genetics and Pathology (IGP), Dag Hammarskjölds väg 20 Uppsala University, Se-751 85 Uppsala, Sweden
Interests: radionuclide imaging; radionuclide therapy; targeted therapy; scaffold proteins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the previous one, “Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development”.

Radionuclide applications in medicine are advancing rapidly. Novel radionuclide imaging probes have been developed to visualize molecular therapeutic targets, paving the way for a new exciting area, theranostics. Novel, promising data suggest that radionuclide therapy might be efficient not only in hematologic malignancies but also in solid tumors. Progress in hardware development has improved the quantification accuracy of SPECT and enabled its use for patient-specific dosimetry, allowing for more personalized and, therefore, more efficient cancer treatment.

This Special Issue aims to highlight current progress in all aspects of methodology development for the application of radionuclides in therapy and diagnosing malignant tumors.

Prof. Dr. Vladimir Tolmachev
Dr. Anzhelika Vorobyeva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted radionuclide therapy
  • theranostics
  • molecular radionuclide imaging
  • response monitoring
  • predictive imaging

Published Papers (3 papers)

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Research

13 pages, 2471 KiB  
Article
A Theranostic Approach to Imaging and Treating Melanoma with 203Pb/212Pb-Labeled Antibody Targeting Melanin
by Rubin Jiao, Kevin J. H. Allen, Mackenzie E. Malo, Orhan Yilmaz, John Wilson, Bryce J. B. Nelson, Frank Wuest and Ekaterina Dadachova
Cancers 2023, 15(15), 3856; https://doi.org/10.3390/cancers15153856 - 29 Jul 2023
Cited by 1 | Viewed by 1386
Abstract
Metastatic melanoma is a deadly disease that claims thousands of lives each year despite the introduction of several immunotherapeutic agents into the clinic over the past decade, inspiring the development of novel therapeutics and the exploration of combination therapies. Our investigations target melanin [...] Read more.
Metastatic melanoma is a deadly disease that claims thousands of lives each year despite the introduction of several immunotherapeutic agents into the clinic over the past decade, inspiring the development of novel therapeutics and the exploration of combination therapies. Our investigations target melanin pigment with melanin-specific radiolabeled antibodies as a strategy to treat metastatic melanoma. In this study, a theranostic approach was applied by first labeling a chimeric antibody targeting melanin, c8C3, with the SPECT radionuclide 203Pb for microSPECT/CT imaging of C57Bl6 mice bearing B16-F10 melanoma tumors. Imaging was followed by radioimmunotherapy (RIT), whereby the c8C3 antibody is radiolabeled with a 212Pb/212Bi “in vivo generator”, which emits cytotoxic alpha particles. Using microSPECT/CT, we collected sequential images of B16-F10 murine tumors to investigate antibody biodistribution. Treatment with the 212Pb/212Bi-labeled c8C3 antibody demonstrated a dose-response in tumor growth rate in the 5–10 µCi dose range when compared to the untreated and radiolabeled control antibody and a significant prolongation in survival. No hematologic or systemic toxicity of the treatment was observed. However, administration of higher doses resulted in a biphasic tumor dose response, with the efficacy of treatment decreasing when the administered doses exceeded 10 µCi. These results underline the need for more pre-clinical investigation of targeting melanin with 212Pb-labeled antibodies before the clinical utility of such an approach can be assessed. Full article
(This article belongs to the Special Issue Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development (Volume II))
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15 pages, 5284 KiB  
Article
Direct Intra-Patient Comparison of Scaffold Protein-Based Tracers, [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3, for Imaging of HER2-Positive Breast Cancer
by Olga Bragina, Vladimir Chernov, Alexey Schulga, Elena Konovalova, Sophia Hober, Sergey Deyev, Jens Sörensen and Vladimir Tolmachev
Cancers 2023, 15(12), 3149; https://doi.org/10.3390/cancers15123149 - 11 Jun 2023
Cited by 3 | Viewed by 1779
Abstract
Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [99mTc]Tc-ADAPT6 and DARPin [99mTc]Tc-(HE)3-G3 in breast cancer patients have demonstrated their safety and indicated their capability to discriminate between HER2-positive and HER2-negative tumours. The objective of this [...] Read more.
Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [99mTc]Tc-ADAPT6 and DARPin [99mTc]Tc-(HE)3-G3 in breast cancer patients have demonstrated their safety and indicated their capability to discriminate between HER2-positive and HER2-negative tumours. The objective of this study was to compare the imaging of HER2-positive tumours in the same patients using [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3. Eleven treatment-naïve female patients (26–65 years) with HER2-positive primary and metastatic breast cancer were included in the study. Each patient was intravenously injected with [99mTc]Tc-ADAPT6, followed by an [99mTc]Tc-(HE)3-G3 injection 3–4 days later and chest SPECT/CT was performed. All primary tumours were clearly visualized using both tracers. The uptake of [99mTc]Tc-ADAPT6 in primary tumours (SUVmax = 4.7 ± 2.1) was significantly higher (p < 0.005) than the uptake of [99mTc]Tc-(HE)3-G3 (SUVmax = 3.5 ± 1.7). There was no significant difference in primary tumour-to-contralateral site values for [99mTc]Tc-ADAPT6 (15.2 ± 7.4) and [99mTc]Tc-(HE)3-G3 (19.6 ± 12.4). All known lymph node metastases were visualized using both tracers. The uptake of [99mTc]Tc-ADAPT6 in all extrahepatic soft tissue lesions was significantly (p < 0.0004) higher than the uptake of [99mTc]Tc-(HE)3-G3. In conclusion, [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 are suitable for the visualization of HER2-positive breast cancer. At the selected time points, [99mTc]Tc-ADAPT6 has a significantly higher uptake in soft tissue lesions, which might be an advantage for the visualization of small metastases. Full article
(This article belongs to the Special Issue Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development (Volume II))
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15 pages, 3545 KiB  
Article
Radionuclide Therapy of HER2-Expressing Xenografts Using [177Lu]Lu-ABY-027 Affibody Molecule Alone and in Combination with Trastuzumab
by Yongsheng Liu, Tianqi Xu, Anzhelika Vorobyeva, Annika Loftenius, Vitalina Bodenko, Anna Orlova, Fredrik Y. Frejd and Vladimir Tolmachev
Cancers 2023, 15(9), 2409; https://doi.org/10.3390/cancers15092409 - 22 Apr 2023
Cited by 3 | Viewed by 1727
Abstract
ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule ZHER2:2891, which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to ZHER2:2891 to reduce renal uptake and increase bioavailability. The [...] Read more.
ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule ZHER2:2891, which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to ZHER2:2891 to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide 177Lu using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [177Lu]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [177Lu]Lu-ABY-027 and the HER2-targeting antibody trastuzumab could enhance this effect. Balb/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts were used as in vivo models. A pre-injection of trastuzumab did not reduce the uptake of [177Lu]Lu-ABY-027 in tumors. Mice were treated with [177Lu]Lu-ABY-027 or trastuzumab as monotherapies and a combination of these therapies. Mice treated with vehicle or unlabeled ABY-027 were used as controls. Targeted monotherapy using [177Lu]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [177Lu]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [177Lu]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors. Full article
(This article belongs to the Special Issue Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development (Volume II))
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Surgery enhances the effectiveness of Peptide Receptor Radionuclide Therapy in Metastatic Gastroenteropancreatic Neuroendocrine Tumors
Authors: Joseph Tobias, Sara Abou Azar, Rushabh Gujarathi, Chih-Yi Liao and Xavier Keutgen*
Affiliation: Joseph Tobias, Sara Abou Azar, Rushabh Gujarathi, Chih-Yi Liao and Xavier Keutgen* University of Chicago, Chicago, Illinois 60637, USA
Abstract: Background: Resection of primary tumor and surgical debulking are part of the armamentarium to treat metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). With the advent of novel systemic therapies such as Peptide Receptor Radionuclide Therapy (PRRT, 177Lutetium-DOTATATE) the role and sequence of surgical therapy in metastatic GEP-NETs might be questioned. Drawn from our own anecdotal experience, we hypothesized that surgical resection prior to PRRT enhances its effectiveness in patients with metastatic GEP-NETs. Methods: This is a retrospective cohort study of 94 patients with metastatic well-differentiated GEP-NETs treated with 177Lutetium-DOTATATE PRRT at a quaternary care center between 2017 and 2023. We compared demographic, pathologic and outcome variables of 60 patients who underwent surgery (resection of primary tumor and/or surgical debulking), to those from 34 patients who never had surgery. The primary outcome was progression-free survival (PFS) according to RECIST. Pre-treatment 68Ga or 64Cu-DOTATATE PET CT were used to calculate tumor volumes (TV) using the MIM Encore workstation. Multivariable regression was used to model the effect of TV on response to PRRT. Results: Both the surgical and non-surgical cohorts were matched in terms of age, sex, tumor grade (I-III) and number of PRRT cycles completed. The surgery cohort had more small bowel NETs (31 vs. 6, p=0.03), but there were no differences in other primary sites between both cohorts. Within the surgery cohort, 58 patients had their primary tumors resected, of which 36 also underwent debulking of metastatic disease. Median TV was 182mL (IQR 86-451) in the surgery cohort compared to 620mL (IQR 380-958) in the no-surgery cohort (p<0.001) prior to initiation of PRRT. Kaplan Meier analysis of median PFS after PRRT was 26.47 months (95% CI, 18.2-30.53) in the surgery cohort compared to 14.97 months (95% CI, 11.50-21.03) in the no-surgery cohort [HR 0.62, p=0.06)]. On multivariable analysis, tumor volume > 300mL (HR = 1.93, p = 0.11), no surgery (HR = 0.51, p = 0.16), colorectal primary site (HR = 5.75, p = 0.03), and chromogranin A levels > 2ULN (HR 3.70, p = 0.005) were independent predictors for progression. Conclusion: Primary tumor resection and surgical debulking enhances the effectiveness of 177Lutetium-DOTATATE PRRT in the treatment of metastatic well-differentiated GEP-NETs. This favorable effect might be the result of lower overall tumor burden achieved through surgical resection.

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