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.

Part of the Department of Oncology-Pathology
Thuy Tran and her research group.
Thuy Tran's research group.

Translational Theranostics Research at Karolinska Institutet

The TRANslational Theranostics Group at Karolinska Institutet, also recognized as Tran Lab, is advancing theranostic radiopharmaceuticals for diagnostic and therapeutic applications.

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.

Methodologies and Infrastructure

The  TRANslational Theranostics Group is based at the Dept of Oncology and Pathology, and Dept of Karolinska Radiopharmacy, both located in Bioclinicum, Solna.  

The Karolinska Radiopharmacy at Karolinska University Hospital has a new-built state-of-the-art radiochemistry facility, equipped with:

  • 2 cyclotrons (PETrace 800, GE)
  • In total 32  research and GMP hotcells (Comecer)
  • Several synthesis modules (GE, Trasis, E&Z, ITM etc) 
  • New analytical instrumentations (Agilent, LabLogic etc) 

We have access to the solid target on one of the cyclotrons and dedicated radiochemistry labs for the preclinical radiometal and radiochemistry development. We collaborate closely with research leaders within target identification and drug screening and utilizing crucial national infrastructure at Scilifelab and the core facilities at KI (such as nanoPET/CT at KERIC). 

Research Support

Our lab research is funded by both internal and external funding through: 

– The Swedish Research Council
– The Swedish Cancer Society
– The Swedish Childhood Cancer Fund
– Radiumhemmets forskningsfonder
– Prostatacancerförbundet
– KID grant, Karolinska Institutet
– Medicinsk Diagnostik Karolinska, MDK kliniknära FoU-medel
– National infrastructure Scilifelab
– The KI corefacilities

Our Research

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]Ga-DOTATOC/[177Lu]Lu-DOTATATE for neuroendocrine tumours and [68Ga]Ga-PSMA-11/[177Lu]Lu-PSMA-617 for 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 platform at DDD/SBCS at Scilifelab. Here below is a violin plot depicting single cell RNA expression of several gens across 10 different NBL tumors (A), and the off target expression from the Human Protein Atlas (B) and the verification of cell surface localization of the top targets using immunofluorescence (C). (Unpublished data).

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 for bringing first-in-class theranostics into patient care.  Image below illustrates the TROP2-targeted antibody localization in an animal model, imaged by a microPET/CT (unpublished data).

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 the 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).  Here below is a figure showing the pressed Ni/Mg foils for production of Co-55 (unpublished data).

Radiometals.

Clinical trials of theranostics at Karolinska

As part of the Theranostic Trial Center, we develop radiochemistry, 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 creating new radiopharmaceuticals for cancer treatment and diagnosis, targeting specific cancer tatargets such as SSTR2, HER2, FAP protein, GRPR, and PD-L1 receptors. Here below is visual abstract of Patients with HER2-low metastatic breast cancer (mBC), with paired biopsy and HER2-PET (Altena et al. JNM 2024).

Illustration of HER2-specific PET imaging in metastatic breast cancer.

Publications

Selected publications

Staff and contact

Group leader

All members of the group

News

12 Jan 2024

Welcome Yucen Tao from NUS to our group!
We have the pleasure to welcome Yucen Tao as a guest PhD student from prof Shawn Chen's group, National University of Singapore (NUS).

 Yucen received his B.S. degree (2019) from Ningxia Medical University and M.Sc. Pharm degree from Shandong University (2022). He is currently a Ph.D. student at NUS and his research focus is on the identification of novel PSMA and CXCR4-targeted radiotheranostics.  

He joins our group for a 6-month KI-NUS exchange program, and will work on in vivo evaluation of PSMA-targeted radiopharmaceutical therapy.

06 December, 2023

PhD defence by Ida Friberger
Many congratulations to Ida Friberger, who gracefully and successfully defended her PhD thesis with the  title: "Optimization of in vivo cell tracking methods with long-lived radionuclides for PET imaging". 

01 December, 2023

Best presentation prize
Well performed and represented by two presentations by Tran group, our postdoc Mélodie Ferrat and PhD student Karl Pettersson Palm at the Swedish Radionuclide Therapy conference in Linköping.  Congratulations to Karl who was awarded the best presentation prize!

Keywords:
Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Radiology, Nuclear Medicine and Medical Imaging
TT
Content reviewer:
Thuy Tran
Erika Rindsjö
22-05-2024