Project openings

Evaluating the DNA damage response upon treatment with radioligand therapy in combination with radiosensitizer

Are you eager to work in a scientific setting while staying connected to real-world applications? Do you want to collaborate with skilled scientists to develop procedures that will create value for future drug development and healthcare? Then making your master’s thesis at Minerva Imaging may be just the right thing for you.

Project description  

Targeted radionuclide therapy (TRT) is an emerging cancer treatment that delivers targeted radiation to tumors. As several radioligand-based drugs will soon become standard-of-care treatments, RLT has recently gained significant attention as a key area of research and development within the pharmaceutical industry. With the increasing clinical use of TRT it becomes evident that some patients do not benefit from the therapy, while others develop a resistance to the therapy after an initial response. Hence, there is a growing interest in understanding the mechanisms of resistance to TRT and the need to develop therapies that are able to enhance its therapeutic effect. As the primary mechanisms of action of TRT is DNA damage, the investigation of DNA damage response (DDR) becomes crucial for optimizing treatment strategies. At Minerva Imaging, we provide validated immunohistochemistry staining protocols for key markers of DNA double-strand breakage to our clients (Figure 1), and we wish to expand this selection with other markers of DNA damage.

Establishing models for radioligand therapy is essential to uncover the mechanisms driving treatment resistance in cancer. We therefore want to develop cancer cell line models to investigate molecular and cellular changes that enable the cells to survive and adapt to TRT. Moreover, the cell lines will be ideal models to screen for TRT sensitizing molecular targets in high-throughput assays.

Figure 1. DNA double strand breaks visualization by staining for γH2AX. Left, γH2AX (purple) in cell nuclei (blue) treated with increasing radiation doses (Gy). Right, quantification of the γH2AX signal by Flow cytometry and Immunocytochemistry (ICC).

Project objectives 

In this project, we will develop different TRT resistant cancer cell line models and in parallel, develop protocols for analyzing DDR marker using histological evaluation and/or flow cytometry. We will then evaluate the DDR of the sensitive and resistant cell line to understand the mechanism of resistance. Finally, and if time, the cells will be included in a screen of known radiosensitizer together with TRT to find possible therapeutic strategies.

Project success criteria 

At the end of the project period the student will have created and characterized TRT resistant cancer cell lines that can be included in further studies focused on the development of novel therapeutics. The student will have gained valuable insights into the drug development industry, developed practical problem-solving skills and improved their communication and collaboration skills while gaining hands-on experience bridging academic learnings and industry practices.

The MI Scholar Program 

As a master student you will be part of our internal Minerva Imaging Scholar Program. The program is designed to support Minerva Imaging’s continued development as a scientifically driven CRO and focuses on developing novel tools and procedures that expand the capabilities in our focus areas.

The project period is 9-12 months, and the start date is flexible although Q3 (August/September), 2025 is preferred. The project is open as both a master’s project and/or research year project. The research year is a unique opportunity to delve deeper into a topic and get a closer look at the world of research and life as a researcher. As a master’s project, it will also be possible to combine the project with a student job at Minerva Imaging. Throughout the project you will be assigned to an internal senior researcher that will supervise you.

Your profile

The ideal candidate is driven by cancer research and enjoys working in an international team. It is essential that you have a positive attitude, are proactive, take ownership of the project and drive it forward. You should be on a relevant master’s program (Human Biology, Molecular Biomedicine, DVM, engineer or other nature and life sciences programs).

Application:

If you are interested in the project and want to learn more, please reach out to Department Manager, Sebastian Gnosa; email: seg@minervaimaging.com. Please submit your application via our website: https://minervaimaging.career.emply.com/ad/master-thesis-project-radiation-resistance/ulmrvz

The application must include a short, motivated cover letter and a CV. Applications are evaluated continuously.

Developing methods to evaluate kidney toxicity after radiopharmaceutical therapy for cancer

Are you eager to work in a scientific setting while staying connected to real-world applications? Do you want to collaborate with skilled scientists to develop procedures that will create value for future drug development and healthcare? Then making your master’s thesis at Minerva Imaging may be just the right thing for you.

Project description

Targeted radiopharmaceutical therapies (TRT) have recently opened new avenues for cancer patients to the extend where radiopharmaceutical drugs have been forecasted to “storm the market”.1

Contrary to conventional radiation therapy which delivers beams of radiation from outside the body to kill tumors inside the body (Figure 1a), TRT delivers specific radiation to tumors and prospective metastasis throughout the body while sparring healthy tissues (Figure 1b).

Most novel TRTs are excreted through the renal system, and in some instances, reabsorbed into the kidney leading to increased radiation exposure and damage to the kidneys (Figure 1c). The treatment may be excellent at eradicating tumors, but the kidney toxicity will be a showstopper for the drug moving to the clinic.

At Minerva Imaging, we want to be the global partner supporting the development of radiopharmaceutical therapies for cancer. To select the most effective and safe drugs, we wish to develop methods to evaluate TRT induced kidney toxicity ultimately guiding and accelerating radiopharmaceutical drug development.

Figure 1 . Dolgin, E. Radioactive drugs emerge from the shadow to storm the market (2018). Nature Biotechnol. 36(12):1125-1127. doi: 10.1038/nbt1218-1125.

Project objectives 

The project aims to develop methods to assess nephrotoxicity after TRT in mice and potentially also minipigs. The objective is to elucidate and establish protocols for assessing key parameters of kidney function and injury by leveraging on various state-of-the-art in vivo and ex vivo equipment and assays. Throughout the project period, the student will have a significant role in identifying and determining key parameters to assess and will get hands-on experience with a variety of methods across our interdisciplinary pharmacology departments, including but not limited to:

• Establishing animal models of late-stage radiation (kidney) toxicity: Treatment planning and administration of single and repeated dose regimens of radiopharmaceutical therapy in animals
• Animal monitoring: Body weight monitoring and establishing clinical observations protocols
• Blood sampling, hematology readouts and plasma assays: Longitudinal assessment of influence on blood parameters and biomarkers linked to renal function/injury
• Non-invasive in vivo imaging: Longitudinal assessment of kidney function with diagnostic tracers, developing optimal imaging protocols
• Macroscopic examinations: Necropsy and organ weights to assess extend of tissue damage
• Microscopic examinations: Immunohistochemistry and autoradiography of kidney tissue sections to evaluate severity of damage with AI software

Project success criteria 

At the end of the project period the student will have developed a platform for screening radiopharmaceutical drug candidates for potential kidney toxicity in small and potentially also in large animal species. The student will have gained valuable insights into the drug development industry, developed practical problem-solving skills and improved their communication and collaboration skills while gaining hands-on experience bridging academic learnings and industry practices.

The MI Scholar Program 

As a master student you will be part of our internal Minerva Imaging Scholar Program. The program is designed to support Minerva Imaging’s continued development as a scientifically driven CRO and focuses on developing novel tools and procedures that expand the capabilities in our focus areas.

The project period is 9-12 months, and the start date is flexible although Q3 (August/September), 2025 is preferred. The project is open as both a master’s project and/or research year project. The research year is a unique opportunity to delve deeper into a topic and get a closer look at the world of research and life as a researcher. As a master’s project, it will also be possible to combine the project with a student job at Minerva Imaging. Throughout the project you will be assigned to an internal senior scientist that will supervise you.

Your profile

The ideal candidate is driven by applied science and enjoys in vivo work. It is essential that you have a positive attitude, are proactive, take ownership of the project and drive it forward. It is also important that you set high quality standards for data deliveries.

You should be on a relevant master’s program (Human Biology, Molecular Biomedicine, DVM, engineer or other nature and life sciences programs). It is an advantage if you have already passed a course in laboratory animal science (FELASA category AD or similar), but it is not a requirement.

Application:

If you are interested in the project and want to learn more, please reach out to Department Manager, Lotte K. Kristensen; email: lkk@minervaimaging.com. Please submit your application via our website: https://minervaimaging.career.emply.com/ad/master-thesis-project-kidney-toxicity/51mxff

The application must include a short, motivated cover letter and a CV. Applications are evaluated continuously.

Are you eager to work in a scientific setting while staying connected to real-world applications? Do you want to collaborate with skilled scientists to develop procedures that will create value for future drug development and healthcare? Then making your master’s thesis at Minerva Imaging may be just the right thing for you.

Project description

Radiotherapy is one of the pillars to treat oncological malignancies. Targeted radionuclide therapy (TRT) is emerging as a promising treatment strategy as well. Unfortunately, resistance to radiation-based therapies remains a clinical challenge. The combination of radiation-based therapies and immune checkpoint inhibitors has synergistic potential and could help to overcome this hurdle.

The effects of radiation on the immune system are of paramount clinical importance. The mechanism between radiation-induced cell damage and immune cells is complex and balances between immune-stimulatory and -inhibitory effects which strongly influence antitumor activity (figure).

Figure: Immune-modulatory effects of radiation (Kleinendorst, Clin Cancer Res, 2022).

Establishing animal models to uncover mechanisms driving radiation resistance in cancer is essential to improve radiopharmaceutical drug development. Evaluating radiation-based therapies in murine tumor models with an intact immune system will help us gain greater understanding of radiation biology, resistance mechanisms, and interaction with immune cells. With this project we are therefore leveraging our expertise in the field.

Project objectives 

The objective of this project is to evaluate radiosensitivity in a panel of clinically-relevant murine syngeneic tumor models and the effect of combining radiotherapy and immune checkpoint inhibition on treatment resistance.

1. In this project you will first establish a library of 5-8 syngeneic mouse models investigating murine tumor sensitivity to external beam radiation (EBR) in immunocompetent mice.
2. Then, 1-2 models (sensitive vs. resistant) will be selected for combination treatment studies of EBR with common immunotherapies, and radiosensitizers.
3. Ex vivo methods on tumors, lymph nodes, and blood will be used to evaluate immune activation and DNA damage response, such as flow cytometry, IHC, IDEXX hematology.
4. If the project allows it, a combination treatment from part II that has shown synergy will be repeated, and mice will undergo molecular imaging to visualize positive CD8 cytotoxic T cells.

Applied methods

• Culturing of cancer cells
• Subcutaneous inoculation of cancer cells
• Treatment with external beam radiation
• Treatment with immune checkpoint inhibitors and radiosensitizers
• In vivo tumor growth monitoring by caliper measurements
• Ex vivo evaluation of tumor microenvironment e.g. flow cytometry
• If relevant, µPET/CT imaging

Project success criteria

At the end of the project period, the student will have created and characterized a library of syngeneic mouse models, and their respective radiosensitivity. Additionally, the student will have evaluated efficacy of EBR and immune checkpoint inhibitor combination treatment, including ex vivo validation. Lastly, if time allowed and results were positive, the student will also have evaluated immune activation in vivo, using molecular imaging. The student will have gained valuable insights into the drug development industry, developed practical problem-solving skills and improved their communication and collaboration skills while gaining hands-on experience bridging academic learnings and industry practices.

The MI Scholar Program 

As a master student you will be part of our internal Minerva Imaging Scholar Program. The program is designed to support Minerva Imaging’s continued development as a scientifically driven CRO and focuses on developing novel tools and procedures that expand the capabilities in our focus areas.

The project period is 9-12 months, and the start date is flexible although Q3 (August/September), 2025 is preferred. The project is open as both a master’s project and/or research year project. The research year is a unique opportunity to delve deeper into a topic and get a closer look at the world of research and life as a researcher. As a master’s project, it will also be possible to combine the project with a student job at Minerva Imaging. Throughout the project you will be assigned to an internal senior scientist that will supervise you.

Your profile

The ideal candidate is driven by applied science and enjoys in vivo work. It is essential that you have a positive attitude, are proactive, take ownership of the project and drive it forward. It is also important that you set high quality standards for data deliveries.

You should be on a relevant master’s program (Human Biology, Molecular Biomedicine, DVM, engineer or other nature and life sciences programs). It is an advantage if you have already passed a course in laboratory animal science (FELASA category AD or similar), but it is not a requirement.

Application:

If you are interested in the project and want to learn more, please reach out to Department Manager, Helle Jacobsen; email: hjj@minervaimaging.com. Please submit your application via our website. The application must include a short, motivated cover letter and a CV. Applications are evaluated continuously.

About Minerva Imaging:

Minerva Imaging is a scientifically driven and integrated CRO and CDMO specialized in targeted radionuclide therapies. We focus on the use of advanced animal models within oncology, cardiovascular diseases, and in vivo molecular imaging for translational research and drug development.

We engage with our sponsors to understand their scientific questions and discuss how our methods and capabilities can provide answers. Our facility located in Ølstykke, Denmark offers best–in–industry fully integrated radiopharmaceutical research, drug development, and manufacturing services.

Minerva Imaging is an equal opportunity employer, and we encourage candidates of all backgrounds and experiences to apply.

Follow us on LinkedIn for the latest news updates or visit www.minervaimaging.com for more information.