Nuclear Medicine & PET

Principal investigator: Anders Sundin, Mark Lubberink, Jens Sörensen

Research in nuclear medicine & PET is primarily aimed at the development of new PET tracers and clinical PET methods, in order to meet clinical demands and facilitate clinical research, and at the diagnosis and treatment of neuroendocrine tumours. Our research covers the entire perspective from substance screening, through radiochemistry and pre-clinical validation, to clinical implementation (”bench to bedside”). Our clinical research focuses on the use of PET to create the prerequisites for personalised medicine, for example in relation to molecular radiotherapy and other high-cost cancer therapies. Furthermore, our research aims to increase the understanding of molecular processes related to various diseases, such as for example the development of multimodality imaging using PET-MRI in relation to metabolic diseases and cancer. To be able to offer a complete platform for the use of PET and PET-MRI in clinical research and drug development, the PET community at Uppsala university and Uppsala university hospital has a high competence in all aspects of PET methodology: chemistry, physics, data-analysis, etc. The research in the nuclear medicine & PET group at the Department of Surgical sciences is performed in close callobration with the PET-MRI group, the pre-clinical PET platform at the Department of Medicinal Chemistry, the Section of Biomedical radiation sciences at the Department of Genetics and Pathology, and the PET centre at Uppsala university hospital, as well as a number of clinical research groups at Uppsala university and Uppsala university hospital.

Project 1: Diagnostics and therapy of neuroendocrine tumours

Project 2: PET & Neurology

Project 3: PET & Oncology

Project 4: PET & Cardiology

Project 5: Other applications of PET

Project 6: PET methodology and physics
 


Project 1: Diagnostics and therapy of neuroendocrine tumours

  • Patient-specific dosimetry for optimization of molecular radiotherapy of neuroendocrine tumours with 177Lu-DOTATATE
  • Use of 68Ga-DOTATOC and DOTATATE PET for patient selection, response evaluation, and improved dosimetry of 177Lu-DOTATATE therapy
Transaxial images of liver demonstrating cases of higher detection rate for 68Ga-DOTATOC (A); higher detection rate for 68Ga-DOTATATE (B); and equal detection rate (C). Irina Velikyan et al. J Nucl Med 2013;55:204-210

  • Dose-response evaluation of 177Lu-DOTATATE therapy

Tumor dose–response relationship for patients with PNETs treated with PRRT using 177Lu-DOTATATE, including tumors larger than 2.2 cm (A) and only tumors larger than 4 cm (B). Ezgi Ilan et al. J Nucl Med 2015;56:177-182

  • Evaluation of 11C-5HTP and 68Ga-DOTATOC PET-MRI
  • Optimization of specific activity of 68Ga-DOTATOC

Members of the group

Anders Sundin, Mattias Sandström, Ulrike Garske, Mark Lubberink, Irina Velikyan, Ezgi Ilan, Ulrika Jahn
 

Project 2: PET & Neurology

Projects include:

  • Evaluation of [18F]THK5317 as a PET tracer for tau pathology in Alzheimer’s disease, in collaboration with Professor Nordberg, Karolinska Institutet
18F-THK5317 PET images in a healthy control (left) and an Alzheimer’s disease patient (right), showing tau accumulation. Top row: parametric images showing tau expression; bottom row: tracer uptake at 70-90 min p.i., normalised to cerebellum.
 
  • Development of [11C]PE2I-PET in the differential diagnosis of Parkinsonism
Parametric images of 11C-PE2I relative delivery (R1) and BPND compared with 123I-FP-CIT and 18F-FDG images, illustrating DAT availability and overall brain functional activity in a patient diagnosed with multiple systems atrophy with atrophy related to cerebellum. a.u. = arbitrary unit. Lieuwe Appel et al. J Nucl Med 2015;56:234-242 (publication 36). The images show that a single 11C-PE2I scan can give the same information as a dual-scan protocol with DATscan and FDG, whilst resulting in a considerable reduced radiation dose.
 
  • Characterization of 18F-flutemetamol as a β-amyloid PET imaging ligand
  • PET and social anxiety disorder; several studies in collaboration with Professor Mats Fredrikson and Professor Tomas Furmark, Uppsala University
  • Low-dose 18F-FDG of the brain
  • Development of 11C-LuAE92686 as a PET tracer for PDE10A in collaboration with Lundbeck AS, and assessment of PDE10A activity in schizophrenic patients in collaboration with Robert Boden, Uppsala University

11C-Lu AE92686 uptake in human brain (sum image 15–90 min after injection). Jan Kehler et al. J Nucl Med 2014;55:1513-1518

  • SVCA function in epileptic patients using 11C-UCBA-PET-MRI
  • Evaluation of stemcell-treated MS patients with 11C-Deprenyl, 11C-PK11195 and 15O-water, in collaboration with Joakim Burman, Uppsala University
  • Neuroinflammation and tau in neurotrauma patients: 11C-PK11195 and 18F-THK5317, in collaboration with Professor Niklas Marklund, Uppsala University

Members of the group

Jens Sörensen, Mark Lubberink, Torsten Danfors, Kerstin Heurling, Lieuwe Appel, Anders Wall, Tanja Kero, Ezgi Ilan, My Jonasson, Johan Lilja, Joao Sousa, David Fällmar 


Project 3: PET & Oncology

Projects include:

  • Development and validation of [68Ga]ABY025 Affibody molecule for diagnosis of HER2-positive breast cancer
Maximum Intensity Projection PET images from two studied patients with wide-spread metastatic breast cancer. A: HER2-negative patient. B: HER2-positive patient. FDG-PET images (A1, B1) and [68Ga]ABY-025 PET images (A2=HER2-negative, B2=HER2-positive) are shown. All images are normalized to SUV 10. Darker colors indicate higher uptake. A 68Ga-ABY025 whole-body scan at 4 h p.i. could discriminate with an accuracy of 100% between HER2-negative and HER2-positive metastases using a SUV threshold of 8. Sörensen et al, Theranostics 2016 (jan)
 

  • Development of 68Ga-labelled PET tracers for oncology
  • Reproducibility of 18F-fluoride PET
  • Various other studies
     

[11C]5-HTP, and [18F]FDG, clearly demonstrating focal GLP-1R-positive lesions that could not be localized by established PET techniques. β-Cells in normal pancreas (red arrow) have significant expression of GLP-1R and can also be visualized by this technique (G). All images are normalized to a standardized uptake value of 1 with no background subtracted.
 

Members of the group

Jens Sörensen, Irina Velikyan, Mark Lubberink, Lieuwe Appel, Naresh Regula, Dan Sandberg, Cecilia Wassberg
 

 Project 4: PET & Cardiology

Projects include:

  • Clinical evaluation of 15O-water-PET, in collaboration with VUmc Amsterdam and Århus University Hospital
  • 11C-PIB for diagnosis of cardiac amyloidosis

Short-axis images of 11C-PIB RI and MBF in (left to right) cardiac amyloidosis patients with high, intermediate, and partially increased 11C-PIB retention and a healthy control. Gunnar Antoni et al. J Nucl Med 2013;54:213-220
 
  • Comparison of regadenason and adenosine in pharmacological stress 15O-water PET, in collaboration with Turku PET Centre.

Members of the group

Jens Sörensen, Tanja Kero, Mark Lubberink, Jonny Nordström, Gunnar Antoni (Medicinal Chemistry)
 

Project 5: Other applications of PET

Projects include:

  • Use of 18F-fluoride PET in hip transplants, in collaboration with Gösta Ullmark (Gävle) and Professor Hans Mallmin
  • Validation of 11C-HTP as a marker for beta cells in the human pancreas, in collaboration with Professor Olle Korsgren and others

Members of the group

Jens Sörensen, Mark Lubberink, Enn Maripuu, Marie Berglund, Lina Carlbom
 

Project 6: PET methodology and physics

Projects include:

  • A clinically feasible protocol with fully automated processing of dynamic 11C-PE2I PET scans for calculation of relative cerebral blood flow and dopamine transporter availability images
Patient with clinically diagnosed multiple system atrophy. A) BPND and R1 parametric images of an 80 min 11C-PE2I scan with co-registered MRI-based cerebellum reference, B) SUVr-1 and R1 parametric images of a 30 min scan with automatically obtained SVCA reference. Jonasson et al, Neuroreceptor Mapping 2014
 
  • Estimation of left ventricular ejection fraction based on parametric 15O-water blood volume images: 5D PET
  • Validation of quantitative dynamic PET-MRI scans in cardiology, neurology and oncology
  • Development and validation of tracer kinetic analysis of various PET tracers (18F-flutemetamol, 18F-THK5317, 68Ga-DOTATATE, 68Ga-ABY025, 11C-PIB in amyloidosis, etc.)

SUV is presented as function of net internalisation rate Ki, determined by tracer kinetic modelling of dynamic PET data, in tumors for 68Ga-DOTATOC (A) and 68Ga-DOTATATE (B). Irina Velikyan et al. J Nucl Med 2013;55:204-210. This data shows that SUV does not correlate linearly with Ki and can probably not be interpreted as a marker of somatostatin receptor density.
 
  • Dosimetry and biodistribution of new PET tracers (68Ga-ABY025, 68Ga-DOTATOC, 68Ga-DOTATATE)
  • Whole-body parametric glucose consumption imaging using serial 18F-FDG PET-MRI scans

Members of the group

Mark Lubberink, Jens Sörensen, Tanja Kero, Jonny Nordström, Mattias Sandström, Joao Sousa, Kerstin Heurling, Ezgi Ilan, Johan Lilja, Emil Johansson, My Jonasson