TRANslational Theranostics Group – Thuy Tran

Our research is dedicated to advancing theranostics using radiopharmaceuticals for diagnostics and therapy. We explore new cancer treatment targets and drug screening while simultaneously develop non-conventional radiometals via solid targets. Our work includes the development of innovative radiotracers and in-depth biological evaluation from in vitro, preclinical to clinical translation.

Thuy Tran and her research group.
Thuy Tran's research group

Our research focuses on the development of targeted radiopharmaceuticals for theranostics, i.e. radioactive drugs that can be used both for therapy and diagnostics.  We perform specifically: 

  • Discovery and identification of novel targets for cancer treatment
  • Drug screening for new drug candidates.
  • Advancement of non-conventional radiometals for diagnostics and therapy
  • Development of radiolabelling methods
  • In vitro evaluation in cell cultures and in vivo evaluations in animal models

Our research group is a diverse and multidisciplinary team at the Department of Oncology and Pathology at the Karolinska Institutet. Many of our members are also clinically active at the Karolinska University Hospital, within the Karolinska Radiopharmacy and the Department of Medical Radiation Physics and Nuclear Medicine. We are physically located in Bioclinicum, campus Solna.

Research projects

About theranostics

The developments of radiopharmaceuticals, radioactive drugs, for targeted therapy and diagnostics, so-called theranostics, have gained significant momentum in cancer medicine over the last decade. It refers to a cutting-edge approach, “see what you treat and treat what you see”, in cancer medicine that combines the therapeutic and diagnostic processes to tailor treatment to individual patients.  

By radiolabel targeting agents (such as small molecules, peptides or antibodies) with a positron-emitting radionuclide (for example, fluorine-18; gallium-68 or zirconium-89) or therapeutic radionuclides (alpha particles using actinium-225 or astatine-211 or beta emitters using lutetium-177 or iodine-131), the molecular features of a cancer target can be noninvasively visualized by positron emission tomography (PET) respectively treated by molecular radiotherapy. A great example of successful theranostic applications currently used in cancer patients is the 68Ga-DOTATOC/177Lu-DOTATATE for neuroendocrine tumours and 68Ga-PSMA-11/177Lu-PSMA-671 and prostate cancers. 

Some of our current research projects:

Targeted radiopharmaceutical therapy for high-risk neuroblastoma (NBL) 

We aim to identify and validate novel targets for targeted alpha therapy (TAT) in high-risk neuroblastoma, which could be effective to irradiate micro-metastasis for improving treatment outcome of high-risk NBL in children. Our current strategy at this early drug development phase is to broadly drug screen both small molecules and large substances (antibodies). 

This project is performed closely with Assistant Prof Kasper Karlsson and Associate Prof Jakob Stenman using the national infrastructure platforms at Scilifelab.

Diagram.

TROP2-targeted radiothernostics in solid tumours

The overall aim of this project is to develop radiotheranostics, i.e. a combination of both therapeutics and diagnostics in one package, based on radiolabelled novel monoclonal antibodies (mAb) targeting TROP-2 (Trophoblast cell surface antigen 2) expression in metastatic solid malignancies, with the focus on the hard-to-treat cancer types: metastatic triple-negative breast cancer (mTNBC), luminal HER2-negative breast cancer and metastatic urothelial cancer (mUC). The radiotheranostics concept utilizing a TROP-2 specific monoclonal antibody will provide a platform for a combination of therapeutics and diagnostics in one package for image-guided therapy, defining the treatment outcome and providing a possibility to individualize treatment. 

This project collaborates with several oncologists and radiologists and the team at the Theranostics Trial Center, TTC, to bring first-in-class theranostics into patient care. 

Radiolabeling of rats with antibodies.

Cyclotron-produced radiometals using solid target

For molecular imaging applications, 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. 

With access to a solid target on one of the Karolinska Radiopharmacy’s 2 cyclotrons, we aim to develop and produce several radiometals with unmet needs in nuclear medicine for labelling different molecules, such as cyclotron-produced gallium-68 (68Ga), titan-45 (45Ti), cobalt-55 (55Co) copper-64/61 (64Cu, 61Cu) and zirconium-89 (89Zr). 

Radiometals.

Clinical trials of theranostics at Karolinska

As part of the Theranostic Trial Center, we develop radiochemistry and labelling methods for bringing the promising radiopharmaceuticals from preclinical to first-in-human studies. We collaborate closely with other research group leaders, investigators, clinicians and sponsors, as well as several corefacilities at Karolinska. 

Our current project focuses on trials of radiopharmaceuticals for cancer treatment and diagnosis, targeting specific cancer targets such as SSTR2, HER2, FAP protein, GRPR, and PD-L1 receptors. 

Publications

Selected publications