Pub Date : 2024-08-01Epub Date: 2024-06-20DOI: 10.1007/s00259-024-06791-x
Tessa Buckle, Daphne D D Rietbergen, Linda de Wit-van der Veen, Margret Schottelius
To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent's pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.
{"title":"Lessons learned in application driven imaging agent design for image-guided surgery.","authors":"Tessa Buckle, Daphne D D Rietbergen, Linda de Wit-van der Veen, Margret Schottelius","doi":"10.1007/s00259-024-06791-x","DOIUrl":"10.1007/s00259-024-06791-x","url":null,"abstract":"<p><p>To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent's pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-24DOI: 10.1007/s00259-023-06522-8
Bianca Michalik, Svenja Engels, Maximilian C Otterbach, Jorina Frerichs, Paula E Suhrhoff, Matthias N van Oosterom, Martin H Maurer, Friedhelm Wawroschek, Alexander Winter
Purpose: To obtain initial data on sentinel lymph node (SLN) visualisation by pre-operative magnetic resonance imaging (MRI) and intra-operative bimodal SLN identification using a new magnetic fluorescent hybrid tracer in prostate cancer (PCa) patients.
Methods: Ten patients at > 5% risk for lymph node (LN) invasion were included. The day before surgery, a magnetic fluorescent hybrid tracer consisting of superparamagnetic iron oxide nanoparticles (SPION) and indocyanine green was transrectally injected into the prostate. Five hours after injection, transversal pelvic MRI scans were recorded and T2*-weighed images were screened for pelvic LNs with SPION uptake. Intra-operatively, magnetically active and/or fluorescent SLNs were detected by a handheld magnetometer and near-infrared fluorescence imaging (FI). Extended pelvic lymph node dissection (PLND) and radical prostatectomy completed the surgery. All resected specimens were checked ex situ for magnetic activity and fluorescence and were histopathologically examined.
Results: Pre-operative MRI identified 145 pelvic LNs with SPION uptake. In total, 75 (median 6, range 3‒13) magnetically active SLNs were resected, including 14 SLNs not seen on MRI. FI identified 89 fluorescent LNs (median 8.5, range 4‒13) of which 15 LNs were not magnetically active. Concordance of the different techniques was 70% for pre-operative MRI vs. magnetometer-guided PLND and 88% for magnetic vs. fluorescent SLN detection.
Conclusion: These are the first promising results of bimodal, magnetic fluorescent SLN detection in PCa patients. Our magnetic fluorescent hybrid approach provides the surgeon a pre-operative lymphatic roadmap by using MRI and intra-operative visual guidance through the application of a fluorescent lymphatic agent. The diagnostic accuracy of our new hybrid approach has to be evaluated in further studies.
Trial registration: DRKS00032808. Registered 04 October 2023, retrospectively registered.
{"title":"A new bimodal approach for sentinel lymph node imaging in prostate cancer using a magnetic and fluorescent hybrid tracer.","authors":"Bianca Michalik, Svenja Engels, Maximilian C Otterbach, Jorina Frerichs, Paula E Suhrhoff, Matthias N van Oosterom, Martin H Maurer, Friedhelm Wawroschek, Alexander Winter","doi":"10.1007/s00259-023-06522-8","DOIUrl":"10.1007/s00259-023-06522-8","url":null,"abstract":"<p><strong>Purpose: </strong>To obtain initial data on sentinel lymph node (SLN) visualisation by pre-operative magnetic resonance imaging (MRI) and intra-operative bimodal SLN identification using a new magnetic fluorescent hybrid tracer in prostate cancer (PCa) patients.</p><p><strong>Methods: </strong>Ten patients at > 5% risk for lymph node (LN) invasion were included. The day before surgery, a magnetic fluorescent hybrid tracer consisting of superparamagnetic iron oxide nanoparticles (SPION) and indocyanine green was transrectally injected into the prostate. Five hours after injection, transversal pelvic MRI scans were recorded and T2*-weighed images were screened for pelvic LNs with SPION uptake. Intra-operatively, magnetically active and/or fluorescent SLNs were detected by a handheld magnetometer and near-infrared fluorescence imaging (FI). Extended pelvic lymph node dissection (PLND) and radical prostatectomy completed the surgery. All resected specimens were checked ex situ for magnetic activity and fluorescence and were histopathologically examined.</p><p><strong>Results: </strong>Pre-operative MRI identified 145 pelvic LNs with SPION uptake. In total, 75 (median 6, range 3‒13) magnetically active SLNs were resected, including 14 SLNs not seen on MRI. FI identified 89 fluorescent LNs (median 8.5, range 4‒13) of which 15 LNs were not magnetically active. Concordance of the different techniques was 70% for pre-operative MRI vs. magnetometer-guided PLND and 88% for magnetic vs. fluorescent SLN detection.</p><p><strong>Conclusion: </strong>These are the first promising results of bimodal, magnetic fluorescent SLN detection in PCa patients. Our magnetic fluorescent hybrid approach provides the surgeon a pre-operative lymphatic roadmap by using MRI and intra-operative visual guidance through the application of a fluorescent lymphatic agent. The diagnostic accuracy of our new hybrid approach has to be evaluated in further studies.</p><p><strong>Trial registration: </strong>DRKS00032808. Registered 04 October 2023, retrospectively registered.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1007/s00259-024-06628-7
Luigi Mansi, Carlo Cavaliere
{"title":"The world of functional and molecular imaging is not only based on radiopharmaceuticals: may EJNMMI become the house of all the images' interpreters?","authors":"Luigi Mansi, Carlo Cavaliere","doi":"10.1007/s00259-024-06628-7","DOIUrl":"10.1007/s00259-024-06628-7","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1007/s00259-024-06847-y
Timo F W Soeterik, Joris G Heetman, Rick Hermsen, Lieke Wever, Jules Lavalaye, Maarten Vinken, Clinton D Bahler, Courtney Yong, Mark Tann, Claudia Kesch, Robert Seifert, Tugce Telli, Peter Ka-Fung Chiu, Kwan Kit Wu, Fabio Zattoni, Laura Evangelista, Emma Segalla, Antonio Barone, Francesco Ceci, Pawel Rajwa, Giancarlo Marra, Elio Mazzone, Jean-Paul A Van Basten, Harm H E Van Melick, Roderick C N Van den Bergh, Giorgio Gandaglia
Purpose: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading.
Methods: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4.
Results: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6).
Conclusion: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.
{"title":"The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.","authors":"Timo F W Soeterik, Joris G Heetman, Rick Hermsen, Lieke Wever, Jules Lavalaye, Maarten Vinken, Clinton D Bahler, Courtney Yong, Mark Tann, Claudia Kesch, Robert Seifert, Tugce Telli, Peter Ka-Fung Chiu, Kwan Kit Wu, Fabio Zattoni, Laura Evangelista, Emma Segalla, Antonio Barone, Francesco Ceci, Pawel Rajwa, Giancarlo Marra, Elio Mazzone, Jean-Paul A Van Basten, Harm H E Van Melick, Roderick C N Van den Bergh, Giorgio Gandaglia","doi":"10.1007/s00259-024-06847-y","DOIUrl":"https://doi.org/10.1007/s00259-024-06847-y","url":null,"abstract":"<p><strong>Purpose: </strong>To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading.</p><p><strong>Methods: </strong>PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUV<sub>max</sub>, PSMA<sub>volume</sub>, and total PSMA accumulation (PSMA<sub>total</sub>) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4.</p><p><strong>Results: </strong>A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUV<sub>max</sub>, PSMA<sub>volume</sub> and PSMA<sub>total</sub> were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUV<sub>max</sub>, 72% (95%CI 67 - 76) for PSMA<sub>volume</sub>, 74% (70 - 79) for PSMA<sub>total</sub> and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUV<sub>max</sub> 0-6.5, 6.5-15, 15-28, > 28, PSMA<sub>vol</sub> 0-2, 2-9, 9-20 and > 20 and PSMA<sub>total</sub> 0-12, 12-98 and > 98). PSMA<sub>volume</sub> was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMA<sub>volume</sub> ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMA<sub>volume</sub> < 2 (OR 6.36, 95%CI 1.47 - 27.6).</p><p><strong>Conclusion: </strong>Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1007/s00259-023-06366-2
Fabrizia Gelardi, Lidija Antunovic
{"title":"New actors in prostate cancer surgical theatre: are we sharpening the eye with optical imaging?","authors":"Fabrizia Gelardi, Lidija Antunovic","doi":"10.1007/s00259-023-06366-2","DOIUrl":"10.1007/s00259-023-06366-2","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-28DOI: 10.1007/s00259-023-06524-6
Anne-Claire Berrens, Matthijs Scheltema, Tobias Maurer, Ken Hermann, Freddie C Hamdy, Sophie Knipper, Paolo Dell'Oglio, Elio Mazzone, Hilda A de Barros, Jonathan M Sorger, Matthias N van Oosterom, Philip D Stricker, Pim J van Leeuwen, Daphne D D Rietbergen, Renato A Valdes Olmos, Sergi Vidal-Sicart, Peter R Carroll, Tessa Buckle, Henk G van der Poel, Fijs W B van Leeuwen
Purpose: Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients.
Methods: One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey®. Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method.
Results: Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions).
Conclusions: This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines.
{"title":"Delphi consensus project on prostate-specific membrane antigen (PSMA)-targeted surgery-outcomes from an international multidisciplinary panel.","authors":"Anne-Claire Berrens, Matthijs Scheltema, Tobias Maurer, Ken Hermann, Freddie C Hamdy, Sophie Knipper, Paolo Dell'Oglio, Elio Mazzone, Hilda A de Barros, Jonathan M Sorger, Matthias N van Oosterom, Philip D Stricker, Pim J van Leeuwen, Daphne D D Rietbergen, Renato A Valdes Olmos, Sergi Vidal-Sicart, Peter R Carroll, Tessa Buckle, Henk G van der Poel, Fijs W B van Leeuwen","doi":"10.1007/s00259-023-06524-6","DOIUrl":"10.1007/s00259-023-06524-6","url":null,"abstract":"<p><strong>Purpose: </strong>Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients.</p><p><strong>Methods: </strong>One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey®. Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method.</p><p><strong>Results: </strong>Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of \"cannot answer\" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions).</p><p><strong>Conclusions: </strong>This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-01-13DOI: 10.1007/s00259-023-06586-6
Manon T A Vreeburg, Maarten L Donswijk, Maarten Albersen, Arie Parnham, Benjamin Ayres, Chris Protzel, Curtis Pettaway, Philippe E Spiess, Oscar R Brouwer
Introduction: The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide.
Main text: DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates.
Conclusion: Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.
{"title":"New EAU/ASCO guideline recommendations on sentinel node biopsy for penile cancer and remaining challenges from a nuclear medicine perspective.","authors":"Manon T A Vreeburg, Maarten L Donswijk, Maarten Albersen, Arie Parnham, Benjamin Ayres, Chris Protzel, Curtis Pettaway, Philippe E Spiess, Oscar R Brouwer","doi":"10.1007/s00259-023-06586-6","DOIUrl":"10.1007/s00259-023-06586-6","url":null,"abstract":"<p><strong>Introduction: </strong>The European Association of Urology (EAU) and the American Society of Clinical Oncology (ASCO) recently issued updated guidelines on penile cancer, emphasising dynamic sentinel node biopsy (DSNB) as the preferred method for surgical staging among patients with invasive penile tumours and no palpable inguinal lymphadenopathy. This paper outlines the rationale behind this new recommendation and describes remaining challenges, as well as strategies for promoting DSNB worldwide.</p><p><strong>Main text: </strong>DSNB offers high diagnostic accuracy with the lowest postoperative complications compared to open or minimally invasive inguinal lymph node dissection (ILND), prompting its preference in the new guidelines. Nevertheless, despite its advantages, there are challenges hampering the widespread adoption of DSNB. This includes the false-negative rate associated with DSNB and the potential negative impact on patient outcome. To address this issue, improvements should be made in several areas, including refining the timing and interpretation of the lymphoscintigraphy and the single photon emission computed tomography/computed tomography images. In addition, the quantity of tracer employed and choice of the injection site for the radiopharmaceutical should be optimised. Finally, limiting the removal of nodes without tracer activity during surgery may help minimise complication rates.</p><p><strong>Conclusion: </strong>Over the years, DSNB has evolved significantly, related to the dedicated efforts and innovations in nuclear medicine and subsequent clinical studies validating its efficacy. It is now strongly recommended for surgical staging among selected penile cancer patients. To optimise DSNB further, multidisciplinary collaborative research is required to improve SN identification for better diagnostic accuracy and fewer complications.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-02-20DOI: 10.1007/s00259-024-06653-6
Francesco Collamati, Silvio Morganti, Matthias N van Oosterom, Lorenzo Campana, Francesco Ceci, Stefano Luzzago, Carlo Mancini-Terracciano, Riccardo Mirabelli, Gennaro Musi, Francesca Nicolanti, Ilaria Orsi, Fijs W B van Leeuwen, Riccardo Faccini
Purpose: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery.
Methods: A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue.
Results: The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation.
Conclusion: This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.
{"title":"First-in-human validation of a DROP-IN β-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm.","authors":"Francesco Collamati, Silvio Morganti, Matthias N van Oosterom, Lorenzo Campana, Francesco Ceci, Stefano Luzzago, Carlo Mancini-Terracciano, Riccardo Mirabelli, Gennaro Musi, Francesca Nicolanti, Ilaria Orsi, Fijs W B van Leeuwen, Riccardo Faccini","doi":"10.1007/s00259-024-06653-6","DOIUrl":"10.1007/s00259-024-06653-6","url":null,"abstract":"<p><strong>Purpose: </strong>In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery.</p><p><strong>Methods: </strong>A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., <sup>68</sup> Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [<sup>68</sup>Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue.</p><p><strong>Results: </strong>The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation.</p><p><strong>Conclusion: </strong>This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-11DOI: 10.1007/s00259-024-06731-9
Patrick A Boland, N P Hardy, A Moynihan, P D McEntee, C Loo, H Fenlon, R A Cahill
Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.
结直肠癌仍然是全球癌症死亡和发病的主要原因。手术是初级治疗的主要治疗方式,而且越来越多地成为二级根治性治疗的主要方式。然而,由于越来越多的患者被诊断为早期和恶性前疾病,表现为大息肉,因此需要从首次内镜检查开始就提高诊断和治疗的精确度。人工智能(AI)领域的快速发展,加上近红外成像技术(目前以吲哚菁绿(ICG)为基础)的广泛应用,可以实现结肠镜组织分类和重大息肉的预后分层,其方式与当代动态放射灌注成像类似,但优势在于可以直接在介入手术时限内完成。它可以为即时数字活检提供一种可解释的方法,从而指导甚至取代传统的镊子活检,并为边缘提供指导(在这两个方面,目前的做法是在明确切除前仅有约 80% 的准确率)。在此,我们将讨论用于直肠癌手术的人工智能增强型 ICG 灌注分析的概念和实践,同时重点介绍近期取得的重要进展。其中包括计算机视觉和时间序列分析方面的突破性进展,可在术中对直肠癌组织的荧光灌注信号进行实时量化和分类,从而在内窥镜下准确区分正常、良性和恶性组织,目前正在进行国际前瞻性验证(地平线欧洲 CLASSICA 研究)。下一阶段的进展可能包括根据术中对特定瘤内荧光信号模式的评估,对小型直肠恶性肿瘤进行详细的数字化特征描述。这可能包括 T 分期和瘤内分子过程分析(如血管生成、分化、炎症成分和肿瘤与基质的比例),有可能准确预测非手术治疗的显微局部反应,从而通过决策支持工具实现个性化治疗。这些进步也适用于目前正在进行临床试验的下一代荧光剂和成像剂。此外,通过提供一种可理解的、适用于详细组织特征描述的可视化方法,这种技术为在手术过程中接受其他人工智能方法铺平了道路,其中可能包括基于整个屏幕/视频细节的深度学习方法。
{"title":"Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art.","authors":"Patrick A Boland, N P Hardy, A Moynihan, P D McEntee, C Loo, H Fenlon, R A Cahill","doi":"10.1007/s00259-024-06731-9","DOIUrl":"10.1007/s00259-024-06731-9","url":null,"abstract":"<p><p>Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2023-11-14DOI: 10.1007/s00259-023-06499-4
Jorrit W A Schoenmakers, Marina López-Álvarez, Frank F A IJpma, Marjan Wouthuyzen-Bakker, James O McNamara, Marleen van Oosten, Paul C Jutte, Jan Maarten van Dijl
Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus.
Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria.
Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min.
Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials.
{"title":"A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.","authors":"Jorrit W A Schoenmakers, Marina López-Álvarez, Frank F A IJpma, Marjan Wouthuyzen-Bakker, James O McNamara, Marleen van Oosten, Paul C Jutte, Jan Maarten van Dijl","doi":"10.1007/s00259-023-06499-4","DOIUrl":"10.1007/s00259-023-06499-4","url":null,"abstract":"<p><strong>Purpose: </strong>Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus.</p><p><strong>Methods: </strong>Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria.</p><p><strong>Results: </strong>38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min.</p><p><strong>Conclusion: </strong>The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}