Pub Date : 2023-10-26DOI: 10.3389/fnume.2023.1273967
Henri Pasquesoone, Aurélien Callaud, Thibaut Carsuzaa, Thomas Chalopin, Maria-Joao Santiago-Ribeiro
TEMPI syndrome (TEMPI) compounds telangiectasias and polycythemia with elevated erythropoietin levels, monoclonal gammopathy, perirenal fluid collections, and intrapulmonary shunt. Although the pathophysiology of this syndrome remains unclarified, prior research has been established that it is a plasma cell neoplasm, often containing less than 10% bone marrow plasma cells. 18 F-FDG PET serves as a valuable instrument for initial staging and treatment monitoring in multiple myeloma management. Thus, 18 F-FDG PET can be legitimately applied for TEMPI assessment. Here, we present the first 18 F-FDG PET images for the initial evaluation and treatment monitoring of TEMPI in a 51-year-old woman, who exhibited polycythemia (EPO:5,448 mIU/ml) without JAK2 mutation, telangiectasias, monoclonal IgG lambda gammopathy (13.9) g/L and 7% dysmorphic plasma cells (CD38 + CD138+), occasionally clustered, in favor of tumoral plasmacytomas. The first PET scan exhibited hypermetabolic diffuse bone marrow, potentially related to polycythemia, accompanied by non-lytic bone hypermetabolic lesions in the femoral and humeral diaphysis, and ametabolic peri-renal fluid collections, brown fat, and pleural talcoma. Post-treatment 18 F-FDG PET (Daratumumab Bortezomib Thalidomide Dexamethasone) revealed a completely reduced signal of bone lesions, suggesting a complete response, which was substantiated both clinically and biologically, with the concurrent disappearance of telangiectasia and the monoclonal component, and the normalization of the EPO level. In future, additional data will be required to confirm the added value of 18 F-FDG PET with TEMPI. Nevertheless, 18 F-FDG PET can be a preferred tool for the extension workup and therapeutic evaluation of TEMPI syndrome.
{"title":"First use of 18F-FDG PET in TEMPI syndrome: can it be used for treatment assessment? A case report","authors":"Henri Pasquesoone, Aurélien Callaud, Thibaut Carsuzaa, Thomas Chalopin, Maria-Joao Santiago-Ribeiro","doi":"10.3389/fnume.2023.1273967","DOIUrl":"https://doi.org/10.3389/fnume.2023.1273967","url":null,"abstract":"TEMPI syndrome (TEMPI) compounds telangiectasias and polycythemia with elevated erythropoietin levels, monoclonal gammopathy, perirenal fluid collections, and intrapulmonary shunt. Although the pathophysiology of this syndrome remains unclarified, prior research has been established that it is a plasma cell neoplasm, often containing less than 10% bone marrow plasma cells. 18 F-FDG PET serves as a valuable instrument for initial staging and treatment monitoring in multiple myeloma management. Thus, 18 F-FDG PET can be legitimately applied for TEMPI assessment. Here, we present the first 18 F-FDG PET images for the initial evaluation and treatment monitoring of TEMPI in a 51-year-old woman, who exhibited polycythemia (EPO:5,448 mIU/ml) without JAK2 mutation, telangiectasias, monoclonal IgG lambda gammopathy (13.9) g/L and 7% dysmorphic plasma cells (CD38 + CD138+), occasionally clustered, in favor of tumoral plasmacytomas. The first PET scan exhibited hypermetabolic diffuse bone marrow, potentially related to polycythemia, accompanied by non-lytic bone hypermetabolic lesions in the femoral and humeral diaphysis, and ametabolic peri-renal fluid collections, brown fat, and pleural talcoma. Post-treatment 18 F-FDG PET (Daratumumab Bortezomib Thalidomide Dexamethasone) revealed a completely reduced signal of bone lesions, suggesting a complete response, which was substantiated both clinically and biologically, with the concurrent disappearance of telangiectasia and the monoclonal component, and the normalization of the EPO level. In future, additional data will be required to confirm the added value of 18 F-FDG PET with TEMPI. Nevertheless, 18 F-FDG PET can be a preferred tool for the extension workup and therapeutic evaluation of TEMPI syndrome.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134906255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-25DOI: 10.3389/fnume.2023.1210982
N. E. Nyakale, C. Aldous, A. A. Gutta, X. Khuzwayo, L. Harry, M. M. Sathekge
Hepatocellular carcinoma (HCC) is a major global health problem. Theragnostic is a term that refers to the integration of diagnostic and therapeutic modalities into a single system for personalized medicine. Theragnostic in HCC involves the use of imaging techniques to diagnose the cancer and assess its characteristics, such as size, location, and extent of spread. Theragnostic involves the use of molecular and genetic tests to identify specific biomarkers that can help guide treatment decisions and post treatment assess the dosimetry and localization of the treatment, thus assisting to guide future treatment. This can be done through either positron emission tomography (PET) scanning or single photon emission tomography (SPECT) using radiolabelled tracers that target specific molecules expressed by HCC cells or radioembolization. This technique can help identify the location and extent of the cancer, as well as provide information on the tumour's metabolic activity and blood supply. In summary, theragnostic is an emerging field that holds promise for improving the diagnosis and treatment of HCC. By combining diagnostic and therapeutic modalities into a single system, theragnostic can help guide personalized treatment decisions and improve patient outcomes.
{"title":"Emerging theragnostic radionuclide applications for hepatocellular carcinoma","authors":"N. E. Nyakale, C. Aldous, A. A. Gutta, X. Khuzwayo, L. Harry, M. M. Sathekge","doi":"10.3389/fnume.2023.1210982","DOIUrl":"https://doi.org/10.3389/fnume.2023.1210982","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major global health problem. Theragnostic is a term that refers to the integration of diagnostic and therapeutic modalities into a single system for personalized medicine. Theragnostic in HCC involves the use of imaging techniques to diagnose the cancer and assess its characteristics, such as size, location, and extent of spread. Theragnostic involves the use of molecular and genetic tests to identify specific biomarkers that can help guide treatment decisions and post treatment assess the dosimetry and localization of the treatment, thus assisting to guide future treatment. This can be done through either positron emission tomography (PET) scanning or single photon emission tomography (SPECT) using radiolabelled tracers that target specific molecules expressed by HCC cells or radioembolization. This technique can help identify the location and extent of the cancer, as well as provide information on the tumour's metabolic activity and blood supply. In summary, theragnostic is an emerging field that holds promise for improving the diagnosis and treatment of HCC. By combining diagnostic and therapeutic modalities into a single system, theragnostic can help guide personalized treatment decisions and improve patient outcomes.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135218429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-13DOI: 10.3389/fnume.2023.1244660
Stephen Harris, James R. Crowley, Nancy Warden
Background The nuclear medicine community has stated that they are using best practices to gain venous access and administer radiopharmaceuticals, and therefore do not contribute to extravasations. We tested this hypothesis qualitatively and quantitatively by evaluating four different perspectives of current radiopharmaceutical administration practices: (1) clinical observations of nuclear medicine technologists on the job, (2) quality improvement (QI) projects, (3) a high-level survey of current practices in 10 acute care hospitals, (4) intravenous (IV) access site data for 29,343 procedures. These four areas were compared to the gold standard of pharmaceutical administration techniques. Results From clinical observations of radiopharmaceutical administrations in adult populations, technologists extensively used 24-gauge peripheral intravenous catheters (PIVCs) and butterfly needles. They also performed direct puncture (straight stick). Technologists predominantly chose veins in areas of flexion (hand, wrist, and antecubital fossa), rather than forearm vessels for IV access placement; in many circumstances, antecubital fossa vessels are chosen first, often without prior assessment for other suitable vessels. For selecting the injection vein, technologists sometimes used infrared vein finders but primarily performed blind sticks. Review of QI projects suggested that smaller gauge needles were contributing factors to extravasations. Additionally, the review of surveys from 10 hospitals revealed an absence of formalized protocols, training, knowledge, and skills necessary to ensure the safety/patency of IV devices prior to the administration of radiopharmaceuticals. Finally, findings from a review of IV access data for 29,343 procedures supported the observations described above. Conclusions We expect that nuclear medicine technologists have the best intentions when providing patient care, but many do not follow venous access best practices; they lack formal protocols, have not received the latest comprehensive training, and do not use the best placement tools and monitoring equipment. Thus, the presumption that most nuclear medicine technologists use best practices may not be accurate. In order to improve radiopharmaceutical administration and patient care, the nuclear medicine community should update technical standards to address the most recent peripheral IV access and administration best practices, provide technologists with vascular visualization tools and the proper training, develop and require annual vascular access competency, and provide active monitoring with center and patient-specific data to create ongoing feedback.
{"title":"Radiopharmaceutical administration practices—Are they best practice?","authors":"Stephen Harris, James R. Crowley, Nancy Warden","doi":"10.3389/fnume.2023.1244660","DOIUrl":"https://doi.org/10.3389/fnume.2023.1244660","url":null,"abstract":"Background The nuclear medicine community has stated that they are using best practices to gain venous access and administer radiopharmaceuticals, and therefore do not contribute to extravasations. We tested this hypothesis qualitatively and quantitatively by evaluating four different perspectives of current radiopharmaceutical administration practices: (1) clinical observations of nuclear medicine technologists on the job, (2) quality improvement (QI) projects, (3) a high-level survey of current practices in 10 acute care hospitals, (4) intravenous (IV) access site data for 29,343 procedures. These four areas were compared to the gold standard of pharmaceutical administration techniques. Results From clinical observations of radiopharmaceutical administrations in adult populations, technologists extensively used 24-gauge peripheral intravenous catheters (PIVCs) and butterfly needles. They also performed direct puncture (straight stick). Technologists predominantly chose veins in areas of flexion (hand, wrist, and antecubital fossa), rather than forearm vessels for IV access placement; in many circumstances, antecubital fossa vessels are chosen first, often without prior assessment for other suitable vessels. For selecting the injection vein, technologists sometimes used infrared vein finders but primarily performed blind sticks. Review of QI projects suggested that smaller gauge needles were contributing factors to extravasations. Additionally, the review of surveys from 10 hospitals revealed an absence of formalized protocols, training, knowledge, and skills necessary to ensure the safety/patency of IV devices prior to the administration of radiopharmaceuticals. Finally, findings from a review of IV access data for 29,343 procedures supported the observations described above. Conclusions We expect that nuclear medicine technologists have the best intentions when providing patient care, but many do not follow venous access best practices; they lack formal protocols, have not received the latest comprehensive training, and do not use the best placement tools and monitoring equipment. Thus, the presumption that most nuclear medicine technologists use best practices may not be accurate. In order to improve radiopharmaceutical administration and patient care, the nuclear medicine community should update technical standards to address the most recent peripheral IV access and administration best practices, provide technologists with vascular visualization tools and the proper training, develop and require annual vascular access competency, and provide active monitoring with center and patient-specific data to create ongoing feedback.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135854885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-09DOI: 10.3389/fnume.2023.1271208
Richard H. Kimura, Andrei Iagaru, H. Henry Guo
This mini review of clinically-evaluated integrin αvβ6 PET-tracers reveals distinct differences in human-biodistribution patterns between linear peptides, including disulfide-stabilized formats, compared to head-to-tail cyclized peptides. All PET tracers mentioned in this mini review were able to delineate disease from normal tissues, but some αvβ6 PET tracers are better than others for particular clinical applications. Each αvβ6 PET tracer was validated for its ability to bind integrin αvβ6 with high affinity. However, all the head-to-tail cyclized peptide PET-tracers reviewed here did not accumulate in the GI-tract, in striking contrast to the linear and disulfide-bonded counterparts currently undergoing clinical evaluation in cancer, IPF and long COVID. Multiple independent investigators have reported the presence of β6 mRNA as well as αvβ6 protein in the GI-tract. Currently, there remains further need for biochemical, clinical, and structural data to satisfactorily explain the state-of-the-art in human αvβ6-imaging.
{"title":"Mini review of first-in-human integrin αvβ6 PET tracers","authors":"Richard H. Kimura, Andrei Iagaru, H. Henry Guo","doi":"10.3389/fnume.2023.1271208","DOIUrl":"https://doi.org/10.3389/fnume.2023.1271208","url":null,"abstract":"This mini review of clinically-evaluated integrin αvβ6 PET-tracers reveals distinct differences in human-biodistribution patterns between linear peptides, including disulfide-stabilized formats, compared to head-to-tail cyclized peptides. All PET tracers mentioned in this mini review were able to delineate disease from normal tissues, but some αvβ6 PET tracers are better than others for particular clinical applications. Each αvβ6 PET tracer was validated for its ability to bind integrin αvβ6 with high affinity. However, all the head-to-tail cyclized peptide PET-tracers reviewed here did not accumulate in the GI-tract, in striking contrast to the linear and disulfide-bonded counterparts currently undergoing clinical evaluation in cancer, IPF and long COVID. Multiple independent investigators have reported the presence of β6 mRNA as well as αvβ6 protein in the GI-tract. Currently, there remains further need for biochemical, clinical, and structural data to satisfactorily explain the state-of-the-art in human αvβ6-imaging.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135095187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-04DOI: 10.3389/fnume.2023.1197397
Nicholas Hardcastle, Yang Liu, Shankar Siva, Steven David
Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [ 18 F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [ 18 F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [ 18 F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [ 18 F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUV max and SUV mean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUV mean in sub-volumes of non-tumour bone receiving doses of 0–20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUV max ; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUV max was observed with higher pre-treatment SUV max . One patient exhibited increased SUV max after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%–34% for non-tumour bone in each dose level.
{"title":"[18F]NaF PET/CT imaging of response to single fraction SABR to bone metastases from breast cancer","authors":"Nicholas Hardcastle, Yang Liu, Shankar Siva, Steven David","doi":"10.3389/fnume.2023.1197397","DOIUrl":"https://doi.org/10.3389/fnume.2023.1197397","url":null,"abstract":"Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [ 18 F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [ 18 F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [ 18 F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [ 18 F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUV max and SUV mean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUV mean in sub-volumes of non-tumour bone receiving doses of 0–20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUV max ; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUV max was observed with higher pre-treatment SUV max . One patient exhibited increased SUV max after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%–34% for non-tumour bone in each dose level.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135591625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-21DOI: 10.3389/fnume.2023.1225034
William Dobney, Louise Mols, Dhruti Mistry, Kevin Tabury, Bjorn Baselet, Sarah Baatout
Ionizing radiation and microgravity are two considerable health risks encountered during deep space exploration. Both have deleterious effects on the human body. On one hand, weightlessness is known to induce a weakening of the immune system, a delayed wound healing and musculoskeletal, cardiovascular, and sensorimotor deconditioning. On the other hand, radiation exposure can lead to long-term health effects such as cancer and cataract, as well as adverse effects to the central nervous and cardiovascular systems. Ionizing radiation originates from three main sources in space: galactic cosmic radiation, solar particle events and solar winds. Furthermore, inside the spacecraft and inside certain space habitats on Lunar and Martian surfaces, the crew is exposed to intravehicular radiation, which arises from nuclear reactions between space radiation and matter. Besides the approaches already in use, such as radiation shielding materials (such as aluminium, water or polyethylene), alternative shielding materials (including boron nanotubes, complex hybrids, composite hybrid materials, and regolith) and active shielding (using fields to deflect radiation particles) are being investigated for their abilities to mitigate the effects of ionizing radiation. From a biological point-of-view, it can be predicted that exposure to ionizing radiation during missions beyond Low Earth Orbit (LEO) will affect the human body in undesirable ways, e.g., increasing the risks of cataract, cardiovascular and central nervous system diseases, carcinogenesis, as well as accelerated ageing. Therefore, it is necessary to assess the risks related to deep space exploration and to develop mitigation strategies to reduce these risks to a tolerable level. By using biomarkers for radiation sensitivity, space agencies are developing extensive personalised medical examination programmes to determine an astronaut's vulnerability to radiation. Moreover, researchers are developing pharmacological solutions (e.g., radioprotectors and radiomitigators) to proactively or reactively protect astronauts during deep space exploration. Finally, research is necessary to develop more effective countermeasures for use in future human space missions, which can also lead to improvements to medical care on Earth. This review will discuss the risks space travel beyond LEO poses to astronauts, methods to monitor astronauts' health, and possible approaches to mitigate these risks.
{"title":"Evaluation of deep space exploration risks and mitigations against radiation and microgravity","authors":"William Dobney, Louise Mols, Dhruti Mistry, Kevin Tabury, Bjorn Baselet, Sarah Baatout","doi":"10.3389/fnume.2023.1225034","DOIUrl":"https://doi.org/10.3389/fnume.2023.1225034","url":null,"abstract":"Ionizing radiation and microgravity are two considerable health risks encountered during deep space exploration. Both have deleterious effects on the human body. On one hand, weightlessness is known to induce a weakening of the immune system, a delayed wound healing and musculoskeletal, cardiovascular, and sensorimotor deconditioning. On the other hand, radiation exposure can lead to long-term health effects such as cancer and cataract, as well as adverse effects to the central nervous and cardiovascular systems. Ionizing radiation originates from three main sources in space: galactic cosmic radiation, solar particle events and solar winds. Furthermore, inside the spacecraft and inside certain space habitats on Lunar and Martian surfaces, the crew is exposed to intravehicular radiation, which arises from nuclear reactions between space radiation and matter. Besides the approaches already in use, such as radiation shielding materials (such as aluminium, water or polyethylene), alternative shielding materials (including boron nanotubes, complex hybrids, composite hybrid materials, and regolith) and active shielding (using fields to deflect radiation particles) are being investigated for their abilities to mitigate the effects of ionizing radiation. From a biological point-of-view, it can be predicted that exposure to ionizing radiation during missions beyond Low Earth Orbit (LEO) will affect the human body in undesirable ways, e.g., increasing the risks of cataract, cardiovascular and central nervous system diseases, carcinogenesis, as well as accelerated ageing. Therefore, it is necessary to assess the risks related to deep space exploration and to develop mitigation strategies to reduce these risks to a tolerable level. By using biomarkers for radiation sensitivity, space agencies are developing extensive personalised medical examination programmes to determine an astronaut's vulnerability to radiation. Moreover, researchers are developing pharmacological solutions (e.g., radioprotectors and radiomitigators) to proactively or reactively protect astronauts during deep space exploration. Finally, research is necessary to develop more effective countermeasures for use in future human space missions, which can also lead to improvements to medical care on Earth. This review will discuss the risks space travel beyond LEO poses to astronauts, methods to monitor astronauts' health, and possible approaches to mitigate these risks.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136130261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20DOI: 10.3389/fnume.2023.1184309
Danae Efremia Bajwa, Evangelia-Alexandra Salvanou, Maria Theodosiou, Theodora S. Koutsikou, Eleni K. Efthimiadou, Penelope Bouziotis, Christos Liolios
Introduction Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m ( 99m Tc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99m Tc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.
{"title":"Radiolabeled iron oxide nanoparticles functionalized with PSMA/BN ligands for dual-targeting of prostate cancer","authors":"Danae Efremia Bajwa, Evangelia-Alexandra Salvanou, Maria Theodosiou, Theodora S. Koutsikou, Eleni K. Efthimiadou, Penelope Bouziotis, Christos Liolios","doi":"10.3389/fnume.2023.1184309","DOIUrl":"https://doi.org/10.3389/fnume.2023.1184309","url":null,"abstract":"Introduction Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m ( 99m Tc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99m Tc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136314063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-14DOI: 10.3389/fnume.2023.1234853
Robin Gutsche, Gizem Gülmüs, Felix M. Mottaghy, Florian Gärtner, Markus Essler, Dirk von Mallek, Hojjat Ahmadzadehfar, Philipp Lohmann, Alexander Heinzel
Objective The treatment with 177 Lutetium PSMA ( 177 Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help to tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomics parameters extracted from pretreatment 68 Ga-PSMA PET images for prediction of treatment response. Methods Forty-five mCRPC patients treated with 177 Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomics features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomics features, and combinations thereof. Further, overall survival was predicted by using the identified radiomics signature and compared to a Cox regression model based on age and PET parameters. Results The machine learning model based on a combined radiomics signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross validation and outperformed models based on age and PET parameters or radiomics features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomics signature showed the best performance to predict the overall survival (C-index, 0.67). Conclusion Our results demonstrate that a machine learning model to predict response to 177 Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomics signature based on pretreatment 68 Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making.
{"title":"Multicentric 68Ga-PSMA PET radiomics for treatment response assessment of 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer","authors":"Robin Gutsche, Gizem Gülmüs, Felix M. Mottaghy, Florian Gärtner, Markus Essler, Dirk von Mallek, Hojjat Ahmadzadehfar, Philipp Lohmann, Alexander Heinzel","doi":"10.3389/fnume.2023.1234853","DOIUrl":"https://doi.org/10.3389/fnume.2023.1234853","url":null,"abstract":"Objective The treatment with 177 Lutetium PSMA ( 177 Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC) has recently been approved by FDA and EMA. Since treatment success is highly variable between patients, the prediction of treatment response and identification of short- and long-term survivors after treatment could help to tailor mCRPC diagnosis and treatment accordingly. The aim of this study is to investigate the value of radiomics parameters extracted from pretreatment 68 Ga-PSMA PET images for prediction of treatment response. Methods Forty-five mCRPC patients treated with 177 Lu-PSMA-617 from two university hospital centers were retrospectively reviewed for this study. Radiomics features were extracted from the volumetric segmentations of metastases in the bone. A random forest model was trained and validated to predict treatment response based on age and conventionally used PET parameters, radiomics features, and combinations thereof. Further, overall survival was predicted by using the identified radiomics signature and compared to a Cox regression model based on age and PET parameters. Results The machine learning model based on a combined radiomics signature of three features and patient age achieved an AUC of 0.82 in 5-fold cross validation and outperformed models based on age and PET parameters or radiomics features (AUC, 0.75 and 0.76, respectively). A Cox regression model based on this radiomics signature showed the best performance to predict the overall survival (C-index, 0.67). Conclusion Our results demonstrate that a machine learning model to predict response to 177 Lu-PSMA treatment based on a combination of radiomics and patient age outperforms a model based on age and PET parameters. Moreover, the identified radiomics signature based on pretreatment 68 Ga-PSMA PET images might be able to identify patients with an improved outcome and serve as a supportive tool in clinical decision making.","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134911457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-12DOI: 10.3389/fnume.2023.1210931
Aliasghar Mortazi, Jayaram K. Udupa, Dewey Odhner, Yubing Tong, Drew A. Torigian
Purpose Tissue radiotracer activity measured from positron emission tomography (PET) images is an important biomarker that is clinically utilized for diagnosis, staging, prognostication, and treatment response assessment in patients with cancer and other clinical disorders. Using PET image values to define a normal range of metabolic activity for quantification purposes is challenging due to variations in patient-related factors and technical factors. Although the formulation of standardized uptake value (SUV) has compensated for some of these variabilities, significant non-standardness still persists. We propose an image processing method to substantially mitigate these variabilities. Methods The standardization method is similar for activity concentration (AC) PET and SUV PET images with some differences and consists of two steps. The calibration step is performed only once for each of AC PET or SUV PET, employs a set of images of normal subjects, and requires a reference object, while the transformation step is executed for each patient image to be standardized. In the calibration step, a standardized scale is determined along with 3 key image intensity landmarks defined on it including the minimum percentile intensity s min , median intensity s m , and high percentile intensity s max . s min and s m are estimated based on image intensities within the body region in the normal calibration image set. The optimal value of the maximum percentile β corresponding to the intensity s max is estimated via an optimization process by using the reference object to optimally separate the highly variable high uptake values from the normal uptake intensities. In the transformation step , the first two landmarks—the minimum percentile intensity p α ( I ), and the median intensity p m ( I )—are found for the given image I for the body region, and the high percentile intensity p β ( I ) is determined corresponding to the optimally estimated high percentile value β . Subsequently, intensities of I are mapped to the standard scale piecewise linearly for different segments. We employ three strategies for evaluation and comparison with other standardization methods: (i) comparing coefficient of variation (CV O ) of mean intensity within test objects O across different normal test subjects before and after standardization; (ii) comparing mean absolute difference (MD O ) of mean intensity within test objects O across different subjects in repeat scans before and after standardization; (iii) comparing CV O of mean intensity across different normal subjects before and after standardization where the scans came from different brands of scanners. Results Our data set consisted of 84 FDG-PET/CT scans of the body torso including 38 normal subjects and two repeat-scans of 23 patients. We utilized one of two objects—liver and spleen—as a reference object and the other for testing. The proposed standardization method reduced CV O and MD O by a factor of 3–8 in comparison to
{"title":"Post-acquisition standardization of positron emission tomography images","authors":"Aliasghar Mortazi, Jayaram K. Udupa, Dewey Odhner, Yubing Tong, Drew A. Torigian","doi":"10.3389/fnume.2023.1210931","DOIUrl":"https://doi.org/10.3389/fnume.2023.1210931","url":null,"abstract":"Purpose Tissue radiotracer activity measured from positron emission tomography (PET) images is an important biomarker that is clinically utilized for diagnosis, staging, prognostication, and treatment response assessment in patients with cancer and other clinical disorders. Using PET image values to define a normal range of metabolic activity for quantification purposes is challenging due to variations in patient-related factors and technical factors. Although the formulation of standardized uptake value (SUV) has compensated for some of these variabilities, significant non-standardness still persists. We propose an image processing method to substantially mitigate these variabilities. Methods The standardization method is similar for activity concentration (AC) PET and SUV PET images with some differences and consists of two steps. The calibration step is performed only once for each of AC PET or SUV PET, employs a set of images of normal subjects, and requires a reference object, while the transformation step is executed for each patient image to be standardized. In the calibration step, a standardized scale is determined along with 3 key image intensity landmarks defined on it including the minimum percentile intensity s min , median intensity s m , and high percentile intensity s max . s min and s m are estimated based on image intensities within the body region in the normal calibration image set. The optimal value of the maximum percentile β corresponding to the intensity s max is estimated via an optimization process by using the reference object to optimally separate the highly variable high uptake values from the normal uptake intensities. In the transformation step , the first two landmarks—the minimum percentile intensity p α ( I ), and the median intensity p m ( I )—are found for the given image I for the body region, and the high percentile intensity p β ( I ) is determined corresponding to the optimally estimated high percentile value β . Subsequently, intensities of I are mapped to the standard scale piecewise linearly for different segments. We employ three strategies for evaluation and comparison with other standardization methods: (i) comparing coefficient of variation (CV O ) of mean intensity within test objects O across different normal test subjects before and after standardization; (ii) comparing mean absolute difference (MD O ) of mean intensity within test objects O across different subjects in repeat scans before and after standardization; (iii) comparing CV O of mean intensity across different normal subjects before and after standardization where the scans came from different brands of scanners. Results Our data set consisted of 84 FDG-PET/CT scans of the body torso including 38 normal subjects and two repeat-scans of 23 patients. We utilized one of two objects—liver and spleen—as a reference object and the other for testing. The proposed standardization method reduced CV O and MD O by a factor of 3–8 in comparison to ","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135884210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05eCollection Date: 2023-01-01DOI: 10.3389/fnume.2023.1258960
Timothy L Bartholow
Extravasation, as distinct from infiltration, is when a potentially toxic agent (e.g., radiographic contrast, chemotherapy, anesthesia or radionuclide) is unintentionally administered to the surrounding tissue instead of directly into the vein. There is an expectation for vascular access in interventional medicine across nearly all specialties that this high frequency, study/treatment critical procedure needs to occur with rare failure and that this failure rate should be characterized in quality assurance. This opinion piece, written by a family practitioner who has served as the chief medical officer for a not-for-profit payer, reflects on our responsibility to be aware as clinicians of known potential harm and disclose to patients before a risk has occurred and if harm has occurred. In this paper, clinical obligations of reporting will be reviewed, which are necessary to maintain and enhance our trust with our patients. In the second half, the perspectives of a not-for-profit payer chief medical officer will be considered.
{"title":"To tell or not to tell … the patient about potential harm.","authors":"Timothy L Bartholow","doi":"10.3389/fnume.2023.1258960","DOIUrl":"10.3389/fnume.2023.1258960","url":null,"abstract":"<p><p>Extravasation, as distinct from infiltration, is when a potentially toxic agent (e.g., radiographic contrast, chemotherapy, anesthesia or radionuclide) is unintentionally administered to the surrounding tissue instead of directly into the vein. There is an expectation for vascular access in interventional medicine across nearly all specialties that this high frequency, study/treatment critical procedure needs to occur with rare failure and that this failure rate should be characterized in quality assurance. This opinion piece, written by a family practitioner who has served as the chief medical officer for a not-for-profit payer, reflects on our responsibility to be aware as clinicians of known potential harm and disclose to patients before a risk has occurred and if harm has occurred. In this paper, clinical obligations of reporting will be reviewed, which are necessary to maintain and enhance our trust with our patients. In the second half, the perspectives of a not-for-profit payer chief medical officer will be considered.</p>","PeriodicalId":73095,"journal":{"name":"Frontiers in nuclear medicine (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48587052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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