TY - JOUR AU - Swider, E.A. AU - Daoudi, K. AU - Staal, A.H.J. AU - Koshkina, O. AU - Riessen, N.K. van AU - Dinther, E.A. van AU - Vries, I.J.M. de AU - Korte, C.L. de AU - Srinivas, M. PY - 2018 UR - https://hdl.handle.net/2066/193511 AB - Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, (19)F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x10(6) cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and (19)F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use. TI - Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, (19)F Magnetic Resonance And Fluorescent Imaging EP - 268 SN - 2206-7418 IS - iss. 3 SP - 258 JF - Nanotheranostics VL - vol. 2 DO - https://doi.org/10.7150/ntno.26208 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/193511/193511.pdf?sequence=1 ER - TY - JOUR AU - Maas, A.H.E.M. AU - Ottevanger, N. AU - Atsma, F. AU - Cramer, M.J. AU - Leiner, T. AU - Poortmans, P. PY - 2016 UR - https://hdl.handle.net/2066/172083 AB - Newly developed treatment strategies for breast cancer have reduced mortality rates over the past decades. Patients with breast cancer represent a heterogeneous population. Differences in the severity of the disease require diverse treatment options. Women have distinct individual risk patterns for cardiovascular disease that may affect their susceptibility to cardiotoxicity during therapy. While breast cancer treatment is targeted more on tumor and patient characteristics, a tailored individual approach with early and late cardiosurveillance is not yet implemented in routine care. Newly available cardiac imaging techniques are better suited to the early detection of cardiotoxicity and should be used more often in those patients at highest risk, as the early intervention afforded will improve their quality of life and prognosis. TI - Cardiovascular surveillance in breast cancer treatment: A more individualized approach is needed EP - 62 SN - 0378-5122 SP - 58 JF - Maturitas VL - vol. 89 DO - https://doi.org/10.1016/j.maturitas.2016.04.015 ER - TY - JOUR AU - Reuvekamp, E.J. AU - Bulten, B.F. AU - Nieuwenhuis, A.A. AU - Meekes, M.R.A. AU - Haan, A.F.J. de AU - Tol, J. AU - Maas, A.H.E.M. AU - Elias-Smale, S.E. AU - Geus-Oei, L.F. de PY - 2016 UR - https://hdl.handle.net/2066/165961 AB - Trastuzumab is successfully used for the treatment of HER2-positive breast cancer. Because of its association with cardiotoxicity, LVEF is monitored by MUGA, though this is a relatively late measure of cardiac function. Diastolic dysfunction (DD) is believed to be an early predictor of cardiac impairment. We evaluate the merit of MUGA-derived diastolic function parameters in the early detection of trastuzumab-induced cardiotoxicity (TIC).77 trastuzumab-treated patients with normal baseline systolic and diastolic function were retrospectively selected (n = 77). All serial MUGA examinations were re-analyzed for systolic and diastolic function parameters. 36 patients (47\%) developed SD and 45 patients (58\%) DD during treatment. Both systolic and diastolic parameters significantly decreased. Of the patients with SD, 24 (67\%) also developed DD. DD developed prior to systolic impairment in 54\% of cases, in 42\% vice versa, while time to occurrence did not differ significantly (P = .52). This also applied to the subgroup of advanced stage breast cancer patients (P = .1).Trastzumab-induced SD and DD can be detected by MUGA. An impairment of MUGA-derived diastolic parameters does not occur prior to SD and therefore cannot be used as earlier predictors of TIC. TI - Does diastolic dysfunction precede systolic dysfunction in trastuzumab-induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA) EP - 832 SN - 1071-3581 SP - 824 JF - Journal of Nuclear Cardiology VL - vol. 23 PS - 9 p. DO - https://doi.org/10.1007/s12350-015-0164-x L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/165961/165961.pdf?sequence=1 ER - TY - JOUR AU - Bulten, B.F. AU - Verberne, H.J. AU - Bellersen, L. AU - Oyen, W.J.G. AU - Sabate-Llobera, A. AU - Mavinkurve-Groothuis, A.M. AU - Kapusta, L. AU - Laarhoven, H.W.M. van AU - Geus-Oei, L.F. de PY - 2015 UR - https://hdl.handle.net/2066/152663 AB - PURPOSE: It remains challenging to identify patients at risk of anthracycline-induced cardiotoxicity. To better understand the different risk-stratifying approaches, we evaluated (123)I-metaiodobenzylguanidine ((123)I-mIBG) scintigraphy and its interrelationship with conventional echocardiography, 2D strain imaging and several biomarkers. METHODS: We performed (123)I-mIBG scintigraphy, conventional and strain echocardiography and biomarker (NT-proBNP, TNF-alpha, galectin-3, IL-6, troponin I, ST-2 and sFlt-1) assessment in 59 breast cancer survivors 1 year after anthracycline treatment. Interobserver and intermethod variability was calculated on planar and SPECT (123)I-mIBG scintigraphy, using the heart/mediastinum (H/M) ratio and washout (WO). Pearson's r and multivariate analyses were performed to identify correlations and independent predictors of (123)I-mIBG scintigraphy results. RESULTS: Delayed planar anterior whole-heart ROI (WH) H/M ratios and WO were the most robust (123)I-mIBG parameters. Significant correlations were observed between (123)I-mIBG parameters and several conventional echo parameters, global longitudinal and radial strain (GLS and GRS) and galectin-3. The highest Pearson's r was observed between delayed H/M ratio and GRS (Pearson's r 0.36, p = 0.01). Multivariate analysis showed that GRS was the only independent predictor of the delayed WH H/M ratio (p = 0.023). CONCLUSION: The delayed planar H/M ratio is the most robust (123)I-mIBG parameter. It correlates with several conventional echocardiographic parameters, GLS, GRS and galectin-3. Of these, only GRS predicts the H/M ratio. TI - Relationship of promising methods in the detection of anthracycline-induced cardiotoxicity in breast cancer patients EP - 967 SN - 0344-5704 IS - iss. 5 SP - 957 JF - Cancer Chemotherapy and Pharmacology VL - vol. 76 PS - 11 p. DO - https://doi.org/10.1007/s00280-015-2874-9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/152663/152663.pdf?sequence=1 ER - TY - JOUR AU - Boxtel, W. van AU - Bulten, B.F. AU - Mavinkurve-Groothuis, A.M. AU - Bellersen, L. AU - Mandigers, C.M. AU - Joosten, L.A.B. AU - Kapusta, L. AU - Geus-Oei, L.F. de AU - Laarhoven, H.W.M. van PY - 2015 UR - https://hdl.handle.net/2066/153493 AB - OBJECTIVE: Assessing a diverse biomarker panel (NT-proBNP, TNF-alpha, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines. METHODS: Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines. RESULTS: 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-alpha and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p 0.1). After simulated ischemia and reperfusion, contractile force was 40 +/- 6 % in the control compared to 39 +/- 6 % in the sunitinib-treated trabeculae during the last final 5 min of reperfusion (n = 12; p > 0.1). Sunitinib at low, but clinically relevant, concentrations does not have a direct effect on function of human atrial cardiomyocytes nor does it attenuate the recovery in contractile force of atrial cardiomyocytes after a period of ischemia. A direct and acute toxic effect on cardiomyocytes does not explain the development of heart failure in patients treated with sunitinib. TI - Sunitinib does not attenuate contractile force following a period of ischemia in isolated human cardiac muscle EP - 443 SN - 1776-2596 IS - iss. 3 SP - 439 JF - Targeted Oncology VL - vol. 10 DO - https://doi.org/10.1007/s11523-014-0351-8 ER - TY - JOUR AU - Willemsen, A.E.C.A.B. AU - Bredie, S.J.H. AU - Lobo, C.M. AU - Vlugt, M.J. van der AU - Kramers, C. PY - 2015 UR - https://hdl.handle.net/2066/154494 AB - The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing wisely', aims to improve quality in healthcare, with attention to cost control. The 'Choosing wisely'-based programme can be applied in the choice of a statin. Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines regarding cardiovascular risk management. Generic atorvastatin is available, and is approximately 25 times cheaper than rosuvastatin in almost equipotent doses. Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL targets can usually be achieved with atorvastatin, and rosuvastatin is not needed. At group level, there are no relevant differences in adverse-events profile between both statins. Atorvastatin and rosuvastatin do have different pharmacokinetic interactions. When changing medication, good provision of information is a prerequisite for patient satisfaction and compliance. We advise use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target is not reached using simvastatin. However, under specific conditions, rosuvastatin should be the treatment of choice. Efficacy and adverse effects should then be evaluated at individual patient level. TI - [Choosing wisely when prescribing statins] SN - 0028-2162 SP - A8695 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 159 ER - TY - JOUR AU - Bulten, B.F. AU - Mavinkurve-Groothuis, A.M.C. AU - Geus-Oei, L.F. de AU - Haan, A.F.J. de AU - Korte, C.L. de AU - Bellersen, L. AU - Laarhoven, H.W.M. van AU - Kapusta, L. PY - 2014 UR - https://hdl.handle.net/2066/136270 AB - To evaluate the role of 2D myocardial strain (rate) imaging in the detection of early subclinical cardiotoxicity in breast cancer survivors treated with an anthracycline-based chemotherapeutic regimen. 57 adult breast cancer survivors were analyzed 1 year after therapy. All patients underwent biomarker analysis and 2D echocardiography consisting of conventional echocardiographic and strain (rate) parameters. Conventional echocardiographic values were normal. Global longitudinal strain was normal, but 18 % of patients showed a >2 SD decrease when individually compared to reference values. This subgroup showed a decrease in end-systolic and end-diastolic volumes and an increase in left ventricular mass. Radial and circumferential strain rates were significantly decreased in the whole study group. 2D myocardial strain (rate) imaging showed abnormalities in breast cancer survivors, while conventional echocardiographic values remained normal, rendering 2D myocardial strain (rate) imaging an interesting tool for the early detection of anthracycline-induced cardiotoxicity. TI - Early myocardial deformation abnormalities in breast cancer survivors EP - 135 SN - 0167-6806 IS - iss. 1 SP - 127 JF - Breast Cancer Research and Treatment VL - vol. 146 DO - https://doi.org/10.1007/s10549-014-2997-4 ER - TY - JOUR AU - Jong, M. de AU - Maas, A.H.E.M. AU - Massuger, L.F.A.G. AU - Hoogerbrugge, N. AU - Hullu, J.A. de PY - 2014 UR - https://hdl.handle.net/2066/133798 AB - BRCA1/2 mutation carriers have an elevated risk of developing breast and ovarian cancer at a relatively young age. Risk-reducing salpingo-oophorectomy is an established strategy to tremendously reduce the risk of ovarian cancer. It is recommended to perform this surgery at age 35-40 years (BRCA1) and at age 40-45 years (BRCA2) resulting in an early and abrupt menopause. BRCA1/2 mutation carriers are potentially at higher risk of cardiovascular diseases due to early surgical menopause, and cardiotoxic effects of adjuvant treatment for breast cancer. Furthermore, preliminary results of experimental studies suggest a possible causative function of the BRCA genes in cardiovascular risk. More research on cardiovascular health risks in BRCA1/2 mutation carriers is needed, especially in the field of cardio-oncology, requiring additional attention to potentially cumulative effects on cardiovascular risks in this specific group of women. TI - BRCA1/2 mutation carriers are potentially at higher cardiovascular risk EP - 171 SN - 1040-8428 IS - iss. 2 SP - 159 JF - Critical Reviews in Oncology Hematology VL - vol. 91 DO - https://doi.org/10.1016/j.critrevonc.2014.01.008 ER - TY - JOUR AU - Geus-Oei, L.F. de AU - Mavinkurve-Groothuis, A.M.C. AU - Bellersen, L. AU - Gotthardt, M. AU - Oyen, W.J.G. AU - Kapusta, L. AU - Laarhoven, H.W.M. van PY - 2013 UR - https://hdl.handle.net/2066/119190 AB - New antitumor agents have resulted in significant survival benefits for cancer patients. However, several agents may have serious cardiovascular side effects. Left ventricular ejection fraction measurement by (99m)Tc multigated radionuclide angiography is regarded as the gold standard to measure cardiotoxicity in adult patients. It identifies left ventricular dysfunction with high reproducibility and low interobserver variability. A decrease in left ventricular ejection fraction, however, is a relatively late manifestation of myocardial damage. Nuclear cardiologic techniques that visualize pathophysiologic processes at the tissue level could detect myocardial injury at an earlier stage. These techniques may give the opportunity for timely intervention to prevent further damage and could provide insights into the mechanisms and pathophysiology of cardiotoxicity caused by anticancer agents. This review provides an overview of past, current, and promising newly developed radiopharmaceuticals and describes the role and recent advances of scintigraphic techniques to measure cardiotoxicity. Both first-order functional imaging techniques (visualizing mechanical [pump] function), such as (99m)Tc multigated radionuclide angiography and (99m)Tc gated blood-pool SPECT, and third-order functional imaging techniques (visualizing pathophysiologic and neurophysiologic processes at the tissue level) are discussed. Third-order functional imaging techniques comprise (123)I-metaiodobenzylguanidine scintigraphy, which images the efferent sympathetic nervous innervations; sympathetic neuronal PET, with its wide range of tracers; (111)In-antimyosin, which is a specific marker for myocardial cell injury and necrosis; (99m)Tc-annexin V scintigraphy, which visualizes apoptosis and cell death; fatty-acid-use scintigraphy, which visualizes the storage of free fatty acids in the lipid pool of the cytosol (which can be impaired by cardiotoxic agents); and (111)In-trastuzumab imaging, to study trastuzumab targeting to the myocardium. To define the prognostic importance and clinical value of each of these functional imaging techniques, prospective clinical trials are warranted. TI - Scintigraphic techniques for early detection of cancer treatment-induced cardiotoxicity EP - 181 SN - 0091-4916 IS - iss. 3 SP - 170 JF - Journal of Nuclear Medicine Technology VL - vol. 41 ER - TY - JOUR AU - Palen, R.L.F. van der AU - Bulten, B.F. AU - Mavinkurve-Groothuis, A.M.C. AU - Bellersen, L. AU - Laarhoven, H.W.M. van AU - Kapusta, L. AU - Geus-Oei, L.F. de PY - 2013 UR - https://hdl.handle.net/2066/125520 AB - Aim: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. Patients, methods:30 neuroblastoma patients were retrospectively assessed on cardiac 123I MIBG uptake and urinary catecholamine dopamine and metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA). Cardiac 123I MIBG uptake was quantified by heart-to-mediastinum (H/M) ratios, which were calculated into standard deviation scores (SDS) using age-specific reference values. Results: In 17 (57%) and 12 patients (40%) H/M ratio measurements were below -1.0 and -2.0 SDS at diagnosis. A significant inverse correlation between the average of urine metabolites HVA and VMA, and H/M ratio SDS was observed (r -.39, p = 0.04). Furthermore, there was a significant correlation between the urinary catecholamine metabolite HVA and H/M ratio SDS (r -.40, p=0.04). Conclusion: Routine calculation of H/M ratios in 123I MIBG scintigrams of neuroblastoma patients is not helpful because it will not identify cardiac ventricular dysfunction in this patient category. A low H/M ratio on 123I MIBG scintigraphy is explained by increased cathecholamine levels secreted by neuroblastoma tumours. TI - Catecholamines influence myocardial 123I MIBG uptake in neuroblastoma patients EP - 234 SN - 0029-5566 IS - iss. 6 SP - 228 JF - Nuklearmedizin. Nuclear Medicine VL - vol. 52 DO - https://doi.org/10.3413/Nukmed-0590-13-05 ER - TY - JOUR AU - Geus-Oei, L.F. de AU - Mavinkurve-Groothuis, A.M.C. AU - Bellersen, L. AU - Gotthardt, M. AU - Oyen, W.J.G. AU - Kapusta, L. AU - Laarhoven, H.W.M. van PY - 2011 UR - https://hdl.handle.net/2066/97337 AB - New antitumor agents have resulted in significant survival benefits for cancer patients. However, several agents may have serious cardiovascular side effects. Left ventricular ejection fraction measurement by (99m)Tc multigated radionuclide angiography is regarded as the gold standard to measure cardiotoxicity in adult patients. It identifies left ventricular dysfunction with high reproducibility and low interobserver variability. A decrease in left ventricular ejection fraction, however, is a relatively late manifestation of myocardial damage. Nuclear cardiologic techniques that visualize pathophysiologic processes at the tissue level could detect myocardial injury at an earlier stage. These techniques may give the opportunity for timely intervention to prevent further damage and could provide insights into the mechanisms and pathophysiology of cardiotoxicity caused by anticancer agents. This review provides an overview of past, current, and promising newly developed radiopharmaceuticals and describes the role and recent advances of scintigraphic techniques to measure cardiotoxicity. Both first-order functional imaging techniques (visualizing mechanical [pump] function), such as (99m)Tc multigated radionuclide angiography and (99m)Tc gated blood-pool SPECT, and third-order functional imaging techniques (visualizing pathophysiologic and neurophysiologic processes at the tissue level) are discussed. Third-order functional imaging techniques comprise (123)I-metaiodobenzylguanidine scintigraphy, which images the efferent sympathetic nervous innervations; sympathetic neuronal PET, with its wide range of tracers; (111)In-antimyosin, which is a specific marker for myocardial cell injury and necrosis; (99m)Tc-annexin V scintigraphy, which visualizes apoptosis and cell death; fatty-acid-use scintigraphy, which visualizes the storage of free fatty acids in the lipid pool of the cytosol (which can be impaired by cardiotoxic agents); and (111)In-trastuzumab imaging, to study trastuzumab targeting to the myocardium. To define the prognostic importance and clinical value of each of these functional imaging techniques, prospective clinical trials are warranted. TI - Scintigraphic techniques for early detection of cancer treatment-induced cardiotoxicity EP - 571 SN - 0161-5505 IS - iss. 4 SP - 560 JF - The Journal of Nuclear Medicine (1978) VL - vol. 52 DO - https://doi.org/10.2967/jnumed.110.082784 ER - TY - JOUR AU - Berends, M. AU - Bokhoven, M.M. van AU - Luijtgaarden, A.C.M. van de AU - Bellersen, L. AU - Hoesel, Q.G.C.M. van AU - Herpen, C.M.L. van PY - 2008 UR - https://hdl.handle.net/2066/69207 AB - In a adolescent women aged 15 and 17 years respectively, severe heart failure developed within a few months of anthracycline chemotherapy given for osteosarcoma. In the guidelines of the European Society of Cardiology, malignancy with a remission duration of less than 5 years is an absolute contraindication to cardiac transplantation. Neither patient was eligible to receive a ventricular assist device (VAD) as a bridge to cardiac transplantation in the Netherlands, but they were accepted in Germany. One patient received a cardiac transplant 13 months later and at the last follow-up check she was in good health with a remission of 3 years. The other patient developed bone metastases 6 months after the VAD implantation. Cardiac transplantation was not a treatment option for her. Dose-dependent cardiotoxicity is a serious complication of the use of anthracyclines. In severe heart failure the prognosis is often worse than in adjuvantly treated malignancies like osteosarcoma. VAD may therefore be a valid option for patients with severe heart failure after anthracycline use for a malignancy. In cases of sustained remission VAD may be the bridge to transplantation. TI - [Ventricular assist device implantation as a bridge to cardiac transplantation in two adolescents with end-stage cardiomyopathy and heart failure as a result of anthracycline use] EP - 2092 SN - 0028-2162 IS - iss. 38 SP - 2088 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 152 ER -