scholarly journals Dosimetric Analysis of the Short-Ranged Particle Emitter 161Tb for Radionuclide Therapy of Metastatic Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2011
Author(s):  
Peter Bernhardt ◽  
Johanna Svensson ◽  
Jens Hemmingsson ◽  
Nicholas P. van der Meulen ◽  
Jan Rijn Zeevaart ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Formation Rate ◽  
Prostate Specific Membrane Antigen ◽  
Targeted Radionuclide Therapy ◽  
Absorbed Doses ◽  
Iodine 131 ◽  
Low Energy Electron ◽  
Dosimetric Analysis ◽  
Specific Membrane ◽  
Yttrium 90

The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.

scholarly journals The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 560 ◽  
Author(s):  
Eline A.M. Ruigrok ◽  
Wytske M. van Weerden ◽  
Julie Nonnekens ◽  
Marion de Jong
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Strategies ◽  
Prostate Specific Membrane Antigen ◽  
Targeted Radionuclide Therapy ◽  
Tumor Uptake ◽  
Research Projects ◽  
Major Focus ◽  
Preclinical Research ◽  
Specific Membrane ◽  
Focus Point

Prostate specific membrane antigen (PSMA) has become a major focus point in the research and development of prostate cancer (PCa) imaging and therapeutic strategies using radiolabeled tracers. PSMA has shown to be an excellent target for PCa theranostics because of its high expression on the membrane of PCa cells and the increase in expression during disease progression. Therefore, numerous PSMA-targeting tracers have been developed and (pre)clinically studied with promising results. However, many of these PSMA-targeting tracers show uptake in healthy organs such as the salivary glands, causing radiotoxicity. Furthermore, not all patients respond to PSMA-targeted radionuclide therapy (TRT). This created the necessity of additional preclinical research studies in which existing tracers are reevaluated and new tracers are developed in order to improve PSMA-TRT by protecting the (PSMA-expressing) healthy organs and improving tumor uptake. In this review we will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers, which will give an indication of where the PSMA-TRT research movement is going and what we can expect in future clinical trials.

scholarly journals Spotlight on PSMA as a new theranostic biomarker for bladder cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Maddalena Tumedei ◽  
Sara Ravaioli ◽  
Federica Matteucci ◽  
Monica Celli ◽  
Ugo De Giorgi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Diagnostic Tests ◽  
Radionuclide Therapy ◽  
Tumor Type ◽  
Prostate Specific Membrane Antigen ◽  
Bladder Tissue ◽  
Tissue Samples ◽  
Specific Membrane ◽  
Psma Expression ◽  
Degree Of Extension

AbstractBladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.

Targeted radionuclide therapy for lung cancer with iodine-131-labeled peptide in a nude-mouse model

2017 ◽  
Vol 28 (5) ◽  
pp. 480-488 ◽  
Author(s):  
Zhenzhu Chen ◽  
Hongyi Gao ◽  
Man Li ◽  
Shun Fang ◽  
Guiping Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Nude Mouse ◽  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy ◽  
Nude Mouse Model ◽  
Iodine 131

scholarly journals Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Michele Iori ◽  
Pier C. Capponi ◽  
Sara Rubagotti ◽  
Luca Rosario Esposizione ◽  
Johanna Seemann ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Radionuclide Therapy ◽  
Automated Synthesis ◽  
Targeted Radionuclide Therapy ◽  
The Mean ◽  
Radiochemical Yields ◽  
Yttrium 90

In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02±0.008 mSv/GBq, 0.01±0.03 mSv/GBq, and 0.01±0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

Phase I Trial of Yttrium-90—Labeled Anti—Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (13) ◽  
pp. 2522-2531 ◽  
Author(s):  
Matthew I. Milowsky ◽  
David M. Nanus ◽  
Lale Kostakoglu ◽  
Shankar Vallabhajosula ◽  
Stanley J. Goldsmith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monoclonal Antibody ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Prostate Specific Membrane Antigen ◽  
Life Threatening ◽  
Indium 111 ◽  
Specific Membrane ◽  
Yttrium 90 ◽  
Androgen Independent

Purpose To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 (90Y-J591) in patients with androgen-independent prostate cancer (PC). Patients and Methods Patients with androgen-independent PC and evidence of disease progression received indium-111–J591 for pharmacokinetic and biodistribution determinations followed 1 week later by 90Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m2. Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Results Twenty-nine patients with androgen-independent PC received 90Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m2, with two patients experiencing thrombocytopenia with non–life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m2 dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. Conclusion The recommended dose for 90Y-J591 is 17.5 mCi/m2. Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of 90Y-J591 in the treatment of patients with PC.

scholarly journals Combination Therapies with PRRT

2021 ◽  
Vol 14 (10) ◽  
pp. 1005
Author(s):  
Anna Yordanova ◽  
Hojjat Ahmadzadehfar
Keyword(s):  
Radionuclide Therapy ◽  
Synergistic Effects ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Targeted Radionuclide Therapy ◽  
Toxicity Profile ◽  
Combination Therapies ◽  
Combined Treatments ◽  
Peptide Receptor ◽  
Yttrium 90

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).

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