Research team Thuy Tran
Tracer Development for Precision Diagnostics and Therapy - Preclinical, Translational and Clinical Studies
Our research focuses on the development of radiotracers for precision diagnostics, therapy and monitoring of diseases, with the emphasis in oncological diseases. We conduct studies including cyclotron production of exotic radiometals using solid target, novel radiotracer developments, and biological evaluation studies in vitro and in vivo to clinical translation.
With the access to a modern, new-built state-of-the art radiochemistry facility, equipped with 2 cyclotrons, a number of research and eGMP hotcells, several synthesis modules and new analytical instrumentations at the Karolinska Radiopharmacy, Karolinska University Hospital, we provide a wide range of radionuclides and tracers for research and clinical studies based on for example 15O, 11C, 18F, 66/67/68Ga, 99mTc, 89Zr and 177Lu. Below are a few examples of our studies:
- Cyclotron-produced radiometals using solid target: For molecular imaging application, it is important to match the physical half-life of a radionuclide with the biological half-life of the molecules that are used; i.e. small molecules with fast kinetics should be labelled with short-lived while long-lived radiometals are well suitable with antibodies that have slow kinetics. The traditionally generator-produced 68Ga and cyclotron-produced 64Cu, and 89Zr are increasingly used in nuclear medicine. We optimize and produce a number of radiometals (see table below) on a solid target that can be used to label different molecules spanning from small molecules (such as FAPI, PSMA), Affibody antibody and its fragments such as single chain variable fragment, scFv.
- Optimization and clinical implementation of cyclotron-produced 68Ga for radiolabelling of clinically used radiopharmaceuticals: Commercially available generators, giving small amounts of 68Ga, are used in both synthesis productions and kit-preparations of radiopharmaceuticals. Today, accessibility to these generators is a problem, both due to production rates and relatively high costs. To meet the demand of 68Ga labelled radiotracers, we aim to develop, refine cyclotron-produced 68Ga for clinical use and to evaluate the feasibility for labelling of the commonly clinically approved tracers such as 68Ga-DOTATOC/68Ga-DOTATATE, 68Ga-PSMA-11 as well as for the newly developed 68Ga-ABY025 and 68Ga-FAPI.
- Explorative and preclinical targeting the Fibroblast Activation Protein, FAP for theranostics applications: FAP is a cell glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodelling, fibrosis, wound healing and tumour growth. High expression of FAP can be found in several carcinomas such as breast, colorectal, prostate and pancreatic cancer that can serve as a feasible target for theranostics, i.e. both molecular imaging and therapy. We aim to explore the targeting of FAP in different carcinomas for theranostics using 68Ga/177Lu-labelled FAP inhibitors, FAPI. We will also develop an 18F-based FAP-tracer to improve the usefulness of a diagnostic tracer since 18F is a better radionuclide for imaging than 68Ga. The potential clinical use of 68Ga-labelled FAPI tracer in pancreatic cancer patients will be investigated in a planned clinical study in collaborations with prof. Rimma Axelsson’s group and oncologists at Karolinska University Hospital.
- Development of radioactive cell-labelling methods for long-term in vivo PET imaging: Cell-based therapy is currently used for treatment of a variety of cancer types such as relapse leukaemia, multiple myeloma and different types of lymphoma. However, many of these treatments still suffer from unpredictable level of efficiency; have several side-effects and severe complications. We develop long-lived radionuclide-based tracers for cell labelling that can provide the necessary information on cell behaviour and migration in vivo with real-time PET imaging. This project is performed in close collaboration with prof. Staffan Holmin’s group and Dr. Mattias Carlsten’s group.
Thuy Tran, PhD, Associate professor, Team leader
Emma Jussing, PhD student
Stefan Milton, Research Associate
Mohammad Moein, PhD, Researcher
Erik Samén, PhD, Researcher
Jonathan Siikanen, PhD, Postdoc
Tetyana Tegnebratt, PhD, Researcher
Rifki Bachtiar, Master student
Emmy Dahlqvist, Master student
Lise-Lotte Schalin, Master student
Visiting address: Akademiska stråket 1, 171 64 Solna
Postal address: Karolinska universitetssjukhuset, J5:20, 171 76 Stockholm
Intern adress: Thuy Tran, J5:20 Bioclinicum
Selected publications from the group
A solid target system with remote handling of irradiated targets for PET cyclotrons.
Siikanen J, Tran TA, Olsson TG, Strand SE, Sandell A
Appl Radiat Isot 2014 Dec;94():294-301
Treatment response assessment with (R)-[11CPAQ PET in the MMTV-PyMT mouse model of breast cancer.
Tegnebratt T, Lu L, Eksborg S, Chireh A, Damberg P, Nikkhou-Aski S, et al
EJNMMI Res 2018 Apr;8(1):25
Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches.
Tegnebratt T, Ruge E, Bader S, Ishii N, Aida S, Yoshimura Y, et al
EJNMMI Res 2014 Dec;4(1):34
Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics.
Timmermand OV, Elgqvist J, Beattie KA, Örbom A, Larsson E, Eriksson SE, et al
Theranostics 2019 ;9(8):2129-2142
Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a (111)In-radiolabelled monoclonal antibody, 11B6.
Timmermand OV, Ulmert D, Evans-Axelsson S, Pettersson K, Bjartell A, Lilja H, et al
EJNMMI Res 2014 Dec;4(1):51