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

X-ray pictures: Transaxial images of liver demonstrating cases of higher detection rate for 68Ga-DOTATOC; higher detection rate for 68Ga-DOTATATE; and equal detection rate. — 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

Charts. Tumor dose–response relationship for patients with PNETs treated with PRRT using 177Lu-DOTATATE, including tumors larger than 2.2 cm and only tumors larger than 4 cm — 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 of¹¹C-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

X-ray pictures: 18F-THK5317 PET images in a healthy control and an Alzheimer’s disease patient. — 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

X-ray pictures: Parametric images of 11C-PE2I relative delivery and BPND compared with 123I-FP-CIT and 18F-FDG images — Parametric images of ¹¹C-PE2I relative delivery (R₁) and BP_ND 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

X-ray picture: 11C-Lu AE92686 uptake in human brain — ¹¹*C-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

X-ray pictures from two studied patients with wide-spread metastatic 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

X-ray picture: [11C]5-HTP, and [18F]FDG, clearly demonstrating focal GLP-1R-positive lesions that could not be localized by established PET techniques — *[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

X-ray picture: Short-axis images of 11C-PIB RI and MBF in cardiac amyloidosis patients with high, intermediate, and partially increased 11C-PIB retention and a healthy control. — 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

x-ray picture: a skull clinically diagnosed multiple system atrophy. — Patient with clinically diagnosed multiple system atrophy. A) BP_ND and R₁ parametric images of an 80 min ¹¹C-PE2I scan with co-registered MRI-based cerebellum reference, B) SUV_r-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.)

Three charts: 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 — SUV is presented as function of net internalisation rate K_i, 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 K_i 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