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Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) is under continuous evaluation as a potential treatment for ovarian cancer. The purpose of this study was to evaluate the effect of chemotherapy, drug concentration and temperature. Materials and Methods: We examined the combined effects of hyperthermia and taxane chemotherapy on the clonogenic survival of the human ovarian carcinoma SHIN-3 cell line in vitro. Results: When hyperthermia was combined with chemotherapy, the median lethal dose (LD50) was equivalent regardless of the duration of exposure, and was independent of the exposure temperature. Taxanes showed a similar LD50 over the temperature range tested. Conclusions: In our study, hyperthermia does not increase the cytotoxic effects of taxanes, at least for the concentrations and durations tested. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Astatine is a rare radioelement belonging to the halogen group. Considering the trace amounts of astatine produced in cyclotrons, its chemistry cannot be evaluated by spectroscopic tools. Analytical tools, provided that they are coupled with a radioactive detection system, may be an alternative way to study its chemistry. In this research work, high performance anion exchange chromatography (HPAEC) coupled to a gamma detector (γ) was used to evaluate astatine species under reducing conditions. Also, to strengthen the reliability of the experiments, a quantitative analysis using a reactive transport model has been done. The results confirm the existence of one species bearing one negative charge in the pH range 2–7.5. With respect to the other halogens, its behavior indicates the existence of negative ion, astatide At−. The methodology was successfully applied to the speciation of the astatine in human serum. Under fixed experimental conditions (pH 7.4–7.5 and redox potential of 250mV) astatine exists mainly as astatide At− and does not interact with the major serum components. Also, the method might be useful for the in vitro stability assessment of 211At-labeled molecules potentially applicable in nuclear medicine. [Copyright &y& Elsevier]

Although peptide radionuclide therapy (PRRT) using a somatostatin analog (SSA) radiolabeled with a beta- emitter: [ 177 Lu]Lu-DOTATATE has shown a good clinical efficacy in neuroendocrine tumors (NETs), most of the patients only achieved tumoral stabilization and rare but severe long-term hematological toxicities have been reported. One of the promising options to improve PRRT is targeted alpha therapy. It is therefore essential to propose animal models that can mimic systemic spread disease, especially microscopic disease such as early stage of NET liver metastases to explore targeted alpha therapy. Herein, we report the evaluation of efficacy and toxicity of [ 225 Ac]Ac-DOTATOC in an original preclinical murine model simulating the development of well-characterized liver metastases of pancreatic NETs with SSTR overexpression., Methods: A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [ 68  Ga]Ga-DOTATOC and [ 18 F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [ 225 Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [ 225 Ac]Ac-DOTATOC 10 days after intraportal graft., Results: Liver tumors showed a high uptake of [ 68  Ga]Ga-DOTATOC and no uptake of [ 18 F]F-FDG confirming the well-differentiated phenotype. All groups treated with [ 225 Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53 days with 240 kBq (p = 0.0001), and 58 days with 2 × 120 kBq (p < 0.0001) vs 28 days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings., Conclusion: [ 225 Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Glioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 ( 211 At-9E7.4)., Methods: We orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistribution, efficacy, toxicity, local and systemic responses were assessed following application of this protocol. The 9E7.4 monoclonal antibody was labelled with iodine-125 ( 125 I) for biodistribution and with astatine-211 ( 211 At) for the other experiments., Findings: The 211 At-9E7.4 TAT demonstrated robust efficacy in reducing orthotopic tumours and achieved improved survival rates in the C57BL/6JRj model, reaching up to 70% with a minimal activity of 100 kBq. Targeting SDC1 ensured the cerebral retention of 211 At over an optimal time window, enabling low-activity administration with a minimal toxicity profile. Moreover, TAT substantially reduced the occurrence of secondary tumours and provided resistance to new tumour development after contralateral rechallenge, mediated through the activation of central and effector memory T cells., Interpretation: The locoregional 211 At-9E7.4 TAT stands as one of the most efficient TAT across all preclinical GB models. This study validates SDC1 as a pertinent therapeutic target for GB and underscores 211 At-9E7.4 TAT as a promising advancement to improve the treatment and quality of life for patients with GB., Funding: This work was funded by the French National Agency for Research (ANR) "France 2030 Investment Plan" Labex Iron [ANR-11-LABX-18-01], The SIRIC ILIAD [INCa-DGOS-INSERM-18011], the French program "Infrastructure d'Avenir en Biologie-Santé" (France Life Imaging) [ANR-11-INBS-0006], the PIA3 of the ANR, integrated to the "France 2030 Investment Plan" [ANR-21-RHUS-0012], and support from Inviscan SAS (Strasbourg, France). It was also related to: the ANR under the frame of EuroNanoMed III (project GLIOSILK) [ANR-19-ENM3-0003-01]; the "Région Pays-de-la-Loire" under the frame of the Target'In project; the "Ligue Nationale contre le Cancer" and the "Comité Départemental de Maine-et-Loire de la Ligue contre le Cancer" (CD49) under the frame of the FusTarG project and the "Tumour targeting, imaging and radio-therapies network" of the "Cancéropôle Grand-Ouest" (France). This work was also funded by the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Nantes, and the University of Angers., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The fifteenth edition of the international workshop organized by the "Tumour Targeting and Radiotherapies network" of the Cancéropôle Grand-Ouest focused on the latest advances in internal and external radiotherapy from different disciplinary angles: chemistry, biology, physics, and medicine. The workshop covered several deliberately diverse topics: the role of artificial intelligence, new tools for imaging and external radiotherapy, theranostic aspects, molecules and contrast agents, vectors for innovative combined therapies, and the use of alpha particles in therapy., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β + and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [ 64 Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [ 64 Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [ 64 Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM.

Using different tracers in positron emission tomography (PET) imaging can bring complementary information on tumor heterogeneities. Ideally, PET images of different tracers should be acquired simultaneously to avoid the bias induced by movement and physiological changes between sequential acquisitions. Previous studies have demonstrated the feasibility of recovering separated PET signals or parameters of two or more tracers injected (quasi-)simultaneously in a single acquisition. In this study, a generic framework in the context of dual-tracer PET acquisition is proposed where no strong kinetic assumptions nor specific tuning of parameters are required. The performances of the framework were assessed through simulations involving the combination of [ 18 F]FCH and [ 18 F]FDG injections, two protocols (90 and 60 min acquisition durations) and various activity ratios between the two injections. Preclinical experiments with the same radiotracers were also conducted. Results demonstrate the ability of the method both to extract separated arterial input functions (AIF) from noisy image-derived input function and to separate the dynamic signals and further estimate kinetic parameters. The compromise between bias and variance associated with the estimation of net influx rate K i shows that it is preferable to use the second injected radiotracer with twice the activity of the first for both 90 min [ 18 F]FCH+[ 18 F]FDG and 60 min [ 18 F]FDG+[ 18 F]FCH protocols. In these optimal settings, the weighted mean-squared-error of the estimated AIF was always less than 7%. The K i bias was similar to the one of single-tracer acquisitions; below 5%. Compared to single-tracer results, the variance of K i was twice more for 90 min dual-tracer scenario and four times more for the 60 min scenario. The generic design of the method makes it easy to use for other pairs of radiotracers and even for more than two tracers. The absence of strong kinetic assumptions and tuning parameters makes it suitable for a possible use in clinical routine., (Creative Commons Attribution license.)

Radioimmunoconjugates have been used for over 30 years in nuclear medicine applications. In the last few years, advances in cancer biology knowledge have led to the identification of new molecular targets specific to certain patient subgroups. The use of these targets in targeted therapies approaches has allowed the developments of specifically tailored therapeutics for patients. As consequence of the PET-imaging progresses, nuclear medicine has developed powerful imaging tools, based on monoclonal antibodies, to in vivo characterization of these tumor biomarkers. This imaging modality known as immuno-positron emission tomography (immuno-PET) is currently in fastest-growing and its medical value lies in its ability to give a non-invasive method to assess the in vivo target expression and distribution and provide key-information on the tumor targeting. Currently, immuno-PET presents promising probes for different nuclear medicine topics as staging/stratification tool, theranostic approaches or predictive/prognostic biomarkers. To develop a radiopharmaceutical drug that can be used in immuno-PET approach, it is necessary to find the best compromise between the isotope choice and the immunologic structure (full monoclonal antibody or derivatives). Through some clinical applications, this paper review aims to discuss the most important aspects of the isotope choice and the usable proteic structure that can be used to meet the clinical needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lugat, Bailly, Chérel, Rousseau, Kraeber-Bodéré, Bodet-Milin and Bourgeois.)

Background: Glioblastoma (GB) is the most common and most aggressive malignant brain tumor. In understanding its resistance to conventional treatments, iron metabolism and related pathways may represent a novel avenue. As for many cancer cells, GB cell growth is dependent on iron, which is tightly involved in red-ox reactions related to radiotherapy effectiveness. From new observations indicating an impact of RX radiations on the expression of ceruloplasmin (CP), an important regulator of iron metabolism, the aim of the present work was to study the functional effects of constitutive expression of CP within GB lines in response to beam radiation depending on the oxygen status (21% O 2 versus 3% O 2 )., Methods and Results: After analysis of radiation responses (Hoechst staining, LDH release, Caspase 3 activation) in U251-MG and U87-MG human GB cell lines, described as radiosensitive and radioresistant respectively, the expression of 9 iron partners (TFR1, DMT1, FTH1, FTL, MFRN1, MFRN2, FXN, FPN1, CP) were tested by RTqPCR and western blots at 3 and 8 days following 4 Gy irradiation. Among those, only CP was significantly downregulated, both at transcript and protein levels in the two lines, with however, a weaker effect in the U87-MG, observable at 3% O 2 . To investigate specific role of CP in GB radioresistance, U251-MG and U87-MG cells were modified genetically to obtain CP depleted and overexpressing cells, respectively. Manipulation of CP expression in GB lines demonstrated impact both on cell survival and on activation of DNA repair/damage machinery (γH2AX); specifically high levels of CP led to increased production of reactive oxygen species, as shown by elevated levels of superoxide anion, SOD1 synthesis and cellular Fe2 + ., Conclusions: Taken together, these in vitro results indicate for the first time that CP plays a positive role in the efficiency of radiotherapy on GB cells., (© 2022. The Author(s).)

The International Myeloma Working Group recently fully incorporated 18 F-FDG PET into multiple myeloma (MM) diagnosis and response evaluation. Moreover, a few studies demonstrated the prognostic value of several biomarkers extracted from this imaging at baseline. Before these 18 F-FDG PET biomarkers could be fully endorsed as risk classifiers by the hematologist community, further characterization of underlying molecular aspects was necessary. Methods: Reported prognostic biomarkers ( 18 F-FDG avidity, SUV max , number of focal lesions, presence of paramedullary disease [PMD] or extramedullary disease) were extracted from 18 F-FDG PET imaging at baseline in a group of 139 patients from CASSIOPET, a companion study of the CASSIOPEIA cohort (ClinicalTrials.gov identifier NCT02541383). Transcriptomic analyses using RNA sequencing were realized on sorted bone marrow plasma cells from the same patients. An association with a high-risk gene expression signature (IFM15), molecular classification, progression-free survival, a stringent clinical response, and minimal residual disease negativity were explored. Results: 18 F-FDG PET results were positive in 79.4% of patients; 14% and 11% of them had PMD and extramedullary disease, respectively. Negative 18 F-FDG PET results were associated with lower levels of expression of hexokinase 2 ( HK2 ) (fold change, 2.1; adjusted P = 0.04) and showed enrichment for a subgroup of patients with a low level of bone disease. Positive 18 F-FDG PET results displayed 2 distinct signatures: either high levels of expression of proliferation genes or high levels of expression of GLUT5 and lymphocyte antigens. PMD and IFM15 were independently associated with a lower level of progression-free survival, and the presence of both biomarkers defined a group of "double-positive" patients at very high risk of progression. PMD and IFM15 were related neither to minimal residual disease assessment nor to a stringent clinical response. Conclusion: Our study confirmed and extended the association between imaging biomarkers and transcriptomic programs in MM. The combined prognostic value of PMD and a high-risk IFM15 signature may help define MM patients with a very high risk of progression., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)