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Publications (10 of 147) Show all publications
Nyström, A., Kiritopoulos, D., Ullmark, G., Sörensen, J., Petrén-Mallmin, M., Milbrink, J., . . . Mallmin, H. (2020). Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial. Journal of Bone and Mineral Research, 35(2), 239-247
Open this publication in new window or tab >>Denosumab Prevents Early Periprosthetic Bone Loss After Uncemented Total Hip Arthroplasty: Results from a Randomized Placebo-Controlled Clinical Trial
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2020 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 35, no 2, p. 239-247Article in journal (Refereed) Published
Abstract [en]

Implant loosening is the most common indication for revision surgery after total hip arthroplasty (THA). Although bone resorption around the implants plays a pivotal role in the pathophysiology of loosening, it is unknown whether potent early inhibition of osteoclasts could mitigate this process and thus reduce the need for revision surgery. We performed a randomized, double-blind, placebo-controlled phase 2 trial in 64 patients aged 35 to 65 years with unilateral osteoarthritis of the hip. They underwent surgery with an uncemented THA and were randomized to either two subcutaneous doses of denosumab (n = 32) or placebo (n = 32) given 1 to 3 days and 6 months after surgery. Patients were followed for 24 months. Primary outcome was periprosthetic bone mineral density (BMD) of the hip at 12 months as measured by dual-energy X-ray absorptiometry (DXA). In addition, [18 F] sodium fluoride positron emission tomography/CT (F-PET) was performed in half of the patients for analysis of periprosthetic standardized uptake value (SUV). Analyses were made according to intention-to-treat principles. The trial was registered at ClinicalTrials.gov 2011-001481-18, NCT01630941. Denosumab potently inhibited early periprosthetic bone loss. After 12 months, BMD in the denosumab group was 32% (95% confidence interval [CI] 22-44) higher in Gruen zone 7 and 11% (95% CI 8-15) higher in zones 1 to 7. After 24 months, the difference in BMD between groups had decreased to 15% (95% CI 4-27) in zone 7 and 4% (95% CI 0-8) in zones 1 to 7. In both groups, SUV increased after surgery, but the increase was less pronounced in the denosumab group. Biochemical markers of bone metabolism decreased in the denosumab group in the first 12 months, but a rebound effect with marker concentrations above baseline was observed after 24 months. Denosumab potently prevents early periprosthetic bone loss after uncemented THA; however, the effect diminishes after discontinuation of treatment. Further research is needed to determine whether this bone loss will prove to be of clinical importance and, if so, whether the positive effect observed in this study could be preserved by either prolonged treatment with denosumab or additional antiresorptive treatment. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
Antiresorptives, Biochemical Markers of Bone Turnover, Clinical Trials, DXA, Implants
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-397531 (URN)10.1002/jbmr.3883 (DOI)000493855100001 ()31589776 (PubMedID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2020-02-20Bibliographically approved
Nielsen, R., Møller, N., Gormsen, L. C., Tolbod, L. P., Hansson, N. H., Sörensen, J., . . . Wiggers, H. (2019). Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation, 139(18), 2129-2141
Open this publication in new window or tab >>Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 18, p. 2129-2141Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential doseresponse relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO 2); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.

METHODS: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37 +/- 3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a doseresponse study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO 2 were evaluated using 11C-acetate positron emission tomography.

RESULTS: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4 +/- 0.3 to 3.3 +/- 0.4 mM (P< 0.001). CO rose by 2.0 +/- 0.2 L/min (P< 0.001) because of an increase in stroke volume of 20 +/- 2 mL (P< 0.001) and heart rate of 7 +/- 2 beats per minute (bpm) (P< 0.001). Left ventricular ejection fraction increased 8 +/- 1% (P< 0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM (P< 0.001). 3-OHB increased MVO 2 without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.

CONCLUSIONS: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
3-hydroxybutyrate, echocardiography, heart failure, ketone bodies, metabolism, positron-emission tomography
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387208 (URN)10.1161/CIRCULATIONAHA.118.036459 (DOI)000468330600008 ()30884964 (PubMedID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Velikyan, I., Schweighoefer, P., Feldwisch, J., Seemann, J., Frejd, F. Y., Lindman, H. & Sörensen, J. (2019). Diagnostic HER2-binding radiopharmaceutical, [Ga-68]Ga-ABY-025, for routine clinical use in breast cancer patients. American Journal of Nuclear Medicine and Molecular Imaging, 9(1), 12-23
Open this publication in new window or tab >>Diagnostic HER2-binding radiopharmaceutical, [Ga-68]Ga-ABY-025, for routine clinical use in breast cancer patients
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2019 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 9, no 1, p. 12-23Article in journal (Refereed) Published
Abstract [en]

[Ga-68]Ga-ABY-025/PET-CT targeting human epidermal growth factor receptor type 2 (HER2) has demonstrated its potential clinical value for the detection and quantification of HER2 in a phase I clinical study with breast cancer patients. Previously, the radiopharmaceutical was prepared manually, however larger scale of multicenter clinical trials and routine healthcare requires automation of the production process to limit the operator radiation dose, improve tracer manufacturing robustness, and provide on-line documentation for good manufacturing practice (GMP) compliance. The production of [Ga-68]Ga-ABY-025 was implemented on the Modular-Lab PharmTrace synthesis platform (Eckert & Ziegler) and disposable cassettes were developed. Pharmaceutical grade Ge-68/Ga-68 generator (GalliaPharm (R)) was used in the study. The active pharmaceutical ingredient starting material ABY-025 (GMP grade) was provided by Affibody AB. The patient examinations were conducted using a Discovery MI PET/CT scanner (20 cm FOV, GE Healthcare). Reproducible and GMP compliant fully automated production of [Ga-68]Ga-ABY-025 was developed. The radiochemical purity of the product was 98.7 +/- 0.6% with total peptide content of 315 +/- 15 mu g (n = 3). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity were controlled and met acceptance criteria. The product was stable at ambient temperature for at least 2 h. The primary tumor and metastasis were detected with SUVmax values of 8.3 and 16.0, respectively. Automated production of [Ga-68]Ga-ABY-025 was established and the process was validated enabling standardized multicenter phase II and III clinical trials and routine clinical use. Patient examinations conformed to the radiopharmaceutical biodistribution observed in the previous phase I study.

Place, publisher, year, edition, pages
E-CENTURY PUBLISHING CORP, 2019
Keywords
Affibody, breast cancer, clinical study, HER2, GMP, gallium-68
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-379777 (URN)000460442600002 ()
Funder
Swedish Cancer SocietyThe Breast Cancer Foundation
Available from: 2019-03-21 Created: 2019-03-21 Last updated: 2019-03-21Bibliographically approved
Ullmark, G., Sörensen, J., Maripuu, E. & Nilsson, O. (2019). Fingerprint pattern of bone mineralisation on cemented and uncemented femoral stems: analysis by [18F]-fluoride-PET in a randomised clinical trial. HIP International, 29(6), 609-617
Open this publication in new window or tab >>Fingerprint pattern of bone mineralisation on cemented and uncemented femoral stems: analysis by [18F]-fluoride-PET in a randomised clinical trial
2019 (English)In: HIP International, ISSN 1120-7000, E-ISSN 1724-6067, Vol. 29, no 6, p. 609-617Article in journal (Refereed) Published
Abstract [en]

Purpose: We present a randomised clinical study using 18F-fluoride positron emission tomography/computed tomography (F-PET/CT) to analyse the osteoblastic part of bone metabolism (new bone mineralisation) in periprosthetic bone adjacent to femoral stems following total hip arthoplasty (THA) surgery. Patients with hip osteoarthritis were randomly assigned to THA surgery with cemented or uncemented femoral components.

Patients and methods: THA was performed on 26 patients (26 cases) with hip osteoarthritis. The patients received either an uncemented HA-coated femoral stem or a cemented one. The contralateral healthy femur was used as referent for normal bone metabolism. The patients were analysed with clinical score, radiography and F-PET/CT preoperatively, and postoperatively at 6 weeks and 6 months. After 2 years, clinical score and radiography was analysed again. We used the Polar Map system for analysing and presenting the PET results in 13 regions of interest adjacent to the whole stem.

Results: The clinical results were good in all patients; there were no major complications. Radiographically, all stems were stable. PET analyses after 6 weeks showed that bone mineralising activity was significantly higher around the uncemented stems, both compared to the cemented group and to the contralateral healthy reference femur group. The cemented group also had elevated activity but only at a barely significant level.

Interpretation: Mineralising activity analysed with F-PET/CT was significantly higher for the uncemented group and also decreased at a slower rate. F-PET/CT is a useful new tool for analysing secondary stabilisation of femoral stems after THA.

Keywords
Bone mineralisation, positron emission tomography, total hip arthroplasty
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-375026 (URN)10.1177/1120700018815404 (DOI)000487029700009 ()30520317 (PubMedID)
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2019-11-01Bibliographically approved
Nielsen, R. R., Sörensen, J., Tolbod, L., Alstrup, A. K., Iversen, P., Frederiksen, C. A., . . . Harms, H. J. (2019). Quantitative estimation of extravascular lung water volume and preload by dynamic 15O-water positron emission tomography. European Heart Journal Cardiovascular Imaging, 20(10), 1120-1128
Open this publication in new window or tab >>Quantitative estimation of extravascular lung water volume and preload by dynamic 15O-water positron emission tomography
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2019 (English)In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 20, no 10, p. 1120-1128Article in journal (Refereed) Published
Abstract [en]

AIMS: Left ventricular filling pressure (preload) can be assessed by pulmonary capillary wedge pressure (PCWP) during pulmonary arterial catheterization (PAC). An emerging method [pulse indexed contour cardiac output (PICCO)] can estimate preload by global end-diastolic volume (GEDV) and congestion as extravascular lung water (EVLW) content. However, no reliable quantitative non-invasive methods are available. Hence, in a porcine model of pulmonary congestion, we evaluated EVLW and GEDV by positron emission tomography (PET). The method was applied in 35 heart failure (HF) patients and 9 healthy volunteers.

METHODS AND RESULTS: Eight pigs were studied. Pulmonary congestion was induced by a combination of beta-blockers, angiotensin-2 agonist and saline infusion. PAC, PICCO, computerized tomography, and 15O-H2O-PET were performed. EVLW increased from 521 ± 76 to 973 ± 325 mL (P < 0.001) and GEDV from 1068 ± 170 to 1254 ± 85 mL (P < 0.001). 15O-H2O-PET measures of EVLW increased from 566 ± 151 to 797 ± 231 mL (P < 0.001) and GEDV from 364 ± 60 to 524 ± 92 mL (P < 0.001). Both EVLW and GEDV measured with PICCO and 15O-H2O-PET correlated (r2 = 0.40, P < 0.001; r2 = 0.40, P < 0.001, respectively). EVLW correlated with Hounsfield units (HU; PICCO: r2 = 0.36, P < 0.001, PET: r2 = 0.46, P < 0.001) and GEDV with PCWP (PICCO: r2 = 0.20, P = 0.01, PET: r2 = 0.29, P = 0.002). In human subjects, measurements were indexed (I) for body surface area. Neither EVLWI nor HU differed between chronic stable HF patients and healthy volunteers (P = 0.11, P = 0.29) whereas GEDVI was increased in HF patients (336 ± 66 mL/m2 vs. 276 ± 44 mL/m2, P = 0.01).

CONCLUSION: The present study demonstrates that 15O-H2O-PET can assess pulmonary congestion and preload quantitatively. Hence, prognostic information from 15O-H2O-PET examinations should be evaluated in clinical trials.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
heart failure, nuclear cardiology and PET, pulmonary congestion, translational research
National Category
Cardiac and Cardiovascular Systems Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-397536 (URN)10.1093/ehjci/jez038 (DOI)000493730100007 ()30887037 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20160746
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2019-11-27Bibliographically approved
Lindström, E., Velikyan, I., Regula, N. K., Alhuseinalkhudhur, A., Sundin, A., Sörensen, J. & Lubberink, M. (2019). Regularized reconstruction of digital time-of-flight Ga-68-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients. Theranostics, 9(12), 3476-3484
Open this publication in new window or tab >>Regularized reconstruction of digital time-of-flight Ga-68-PSMA-11 PET/CT for the detection of recurrent disease in prostate cancer patients
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2019 (English)In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 9, no 12, p. 3476-3484Article in journal (Refereed) Published
Abstract [en]

Accurate localization of recurrent prostate cancer (PCa) is critical, especially if curative therapy is intended. With the aim to optimize target-to-background uptake ratio in Ga-68-PSMA-11 PET, we investigated the image quality and quantitative measures of regularized reconstruction by block-sequential regularized expectation maximization (BSREM).

Methods:

The study encompassed retrospective reconstruction and analysis of 20 digital time-of-flight (TOF) PET/CT examinations acquired 60 min post injection of 2 MBq/kg of Ga-68-PSMA-11 in PCa patients with biochemical relapse after primary treatment. Reconstruction by ordered-subsets expectation maximization (OSEM; 3 iterations, 16 subsets, 5 mm gaussian postprocessing filter) and BSREM (beta-values of 100-1600) were used, both including TOF and point spread function (PSF) recovery. Background variability (BV) was measured by placing a spherical volume of interest in the right liver lobe and defined as the standard deviation divided by the mean standardized uptake value (SUV). The image quality was evaluated in terms of signal-to-noise ratio (SNR) and signal-to-background ratio (SBR), using SUVmax of the lesions. A visual assessment was performed by four observers.

Results:

OSEM reconstruction produced images with a BV of 15%, whereas BSREM with a beta-value above 300 resulted in lower BVs than OSEM (36% with beta 100, 8% with beta 1300). Decreasing the acquisition duration from 2 to 1 and 0.5 min per bed position increased BV for both reconstruction methods, although BSREM with beta-values equal to or higher than 800 and 1200, respectively, kept the BV below 15%. In comparison of BSREM with OSEM, the mean SNR improved by 25 to 66% with an increasing beta-value in the range of 200-1300, whereas the mean SBR decreased with an increasing beta-value, ranging from 0 to 125% with a beta-value of 100 and 900, respectively. Decreased acquisition duration resulted in beta-values of 800 to 1000 and 1200 to 1400 for 1 and 0.5 min per bed position, respectively, producing improved image quality measures compared with OSEM at a full acquisition duration of 2 min per bed position. The observer study showed a slight overall preference for BSREM beta 900 although the interobserver variability was high.

Conclusion:

BSREM image reconstruction with beta-values in the range of 400-900 resulted in lower BV and similar or improved SNR and SBR in comparison with OSEM.

Keywords
Ga-68-PSMA-11, prostate cancer, PET/CT, image reconstruction, BSREM, interobserver variability
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-388045 (URN)10.7150/thno.31970 (DOI)000469953000006 ()
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Lilja, J., Leuzy, A., Chiotis, K., Savitcheva, I., Sörensen, J. & Nordberg, A. (2019). Spatial normalization of 18F-Flutemetamol PET images using an adaptive principal-component template. Journal of Nuclear Medicine, 60(2), 285-291
Open this publication in new window or tab >>Spatial normalization of 18F-Flutemetamol PET images using an adaptive principal-component template
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2019 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 60, no 2, p. 285-291Article in journal (Refereed) Published
Abstract [en]

Though currently approved for visual assessment only, there is evidence to suggest that quantification of amyloid-β (Aβ) PET images may reduce interreader variability and aid in the monitoring of treatment effects in clinical trials. Quantification typically involves a regional atlas in standard space, requiring PET images to be spatially normalized. Different uptake patterns in Aβ-positive and Aβ-negative subjects, however, make spatial normalization challenging. In this study, we proposed a method to spatially normalize 18F-flutemetamol images using a synthetic template based on principal-component images to overcome these challenges.

Methods: 18F-flutemetamol PET and corresponding MR images from a phase II trial (n = 70), including subjects ranging from Aβ-negative to Aβ-positive, were spatially normalized to standard space using an MR-driven registration method (SPM12). 18F-flutemetamol images were then intensity-normalized using the pons as a reference region. Principal-component images were calculated from the intensity-normalized images. A linear combination of the first 2 principal-component images was then used to model a synthetic template spanning the whole range from Aβ-negative to Aβ-positive. The synthetic template was then incorporated into our registration method, by which the optimal template was calculated as part of the registration process, providing a PET-only–driven registration method. Evaluation of the method was done in 2 steps. First, coregistered gray matter masks generated using SPM12 were spatially normalized using the PET- and MR-driven methods, respectively. The spatially normalized gray matter masks were then visually inspected and quantified. Second, to quantitatively compare the 2 registration methods, additional data from an ongoing study were spatially normalized using both methods, with correlation analysis done on the resulting cortical SUV ratios.

Results: All scans were successfully spatially normalized using the proposed method with no manual adjustments performed. Both visual and quantitative comparison between the PET- and MR-driven methods showed high agreement in cortical regions. 18F-flutemetamol quantification showed strong agreement between the SUV ratios for the PET- and MR-driven methods (R2 = 0.996; pons reference region).

Conclusion: The principal-component template registration method allows for robust and accurate registration of 18F-flutemetamol images to a standardized template space, without the need for an MR image.

Keywords
Alzheimer disease, amyloid-beta, PET, F-18-flutemetamol, adaptive template
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-357431 (URN)10.2967/jnumed.118.207811 (DOI)000457479800030 ()29903930 (PubMedID)
Funder
VINNOVA, 2013-05175
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2019-03-07Bibliographically approved
Harms, H. J., Hansson, N. H., Kero, T., Baron, T., Tolbod, L. P., Kim, W. Y., . . . Sörensen, J. (2018). Automatic calculation of myocardial external efficiency using a single 11C-acetate PET scan.. Journal of Nuclear Cardiology, 25(6), 1937-1944
Open this publication in new window or tab >>Automatic calculation of myocardial external efficiency using a single 11C-acetate PET scan.
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2018 (English)In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 6, p. 1937-1944Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating.

METHODS AND RESULTS: Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P < 0.001) without significant bias. MEEPET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P = 0.004). MEEPET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P = 0.009).

CONCLUSION: A single 11C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease.

Keywords
11C-acetate, Myocardial efficiency, myocardial energetics, positron emission tomography
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-356783 (URN)10.1007/s12350-018-1338-0 (DOI)000452340400009 ()29946824 (PubMedID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2019-04-17Bibliographically approved
Vorobyeva, A., Westerlund, K., Mitran, B., Altai, M., Rinne, S. S., Sörensen, J., . . . Tolmachev, V. (2018). Development of a PET Imaging Approach for Selection of Patients for Affibody-Based PNA-Mediated Pretargeted Radionuclide Therapy. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY.. European Journal of Nuclear Medicine and Molecular Imaging, 45(Supplement 1), S104-S104
Open this publication in new window or tab >>Development of a PET Imaging Approach for Selection of Patients for Affibody-Based PNA-Mediated Pretargeted Radionuclide Therapy
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement 1, p. S104-S104Article in journal, Meeting abstract (Other academic) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-373340 (URN)10.1007/s00259-018-4148-3 (DOI)000449266201004 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY.
Note

Meeting Abstract: OP-313

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Vorobyeva, A., Westerlund, K., Mitran, B., Altai, M., Rinne, S., Sörensen, J., . . . Karlström, A. E. (2018). Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy. Scientific Reports, 8, Article ID 9643.
Open this publication in new window or tab >>Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9643Article in journal (Refereed) Published
Abstract [en]

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide Lu-177 extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe Z(HER2:342)SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. (68)GaHP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted Lu-177-HP2. The uptake of both Ga-68-Z(HER2:342)SR-HP1 and Ga-68-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of Ga-68-HP2 correlated better with the uptake of Lu-177-HP2 than the uptake of Ga-68 Z(HER2:342) SR-HP1. The use of Ga-68-HP2 as a theranostics counterpart would be preferable approach for clinical translation.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-360010 (URN)10.1038/s41598-018-27886-0 (DOI)000436078500006 ()29942011 (PubMedID)
Funder
Swedish Research Council, 2015-02353Swedish Research Council, 2015-02509Swedish Research Council, 2016-05207VINNOVA, 2015-02509Swedish Cancer Society, CAN 2015/350Swedish Cancer Society, 2014/474Swedish Society for Medical Research (SSMF)
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5738-9983

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