Group Eva Forssell-Aronsson

Research summary

Many cancer patients are difficult to cure, especially when having metastatic disease. Systemic therapy with radiopharmaceuticals could then be beneficial, due to the possibility to reach all tumour cells spread in the body. New knowledge regarding tumour biology, pathology and molecular biology demonstrate more tumour specific features/biomarkers that can be used for development of more specific radiopharmaceuticals and treatment strategies.

Our overall aim is 1) to study the possibilities to develop, optimise and apply new radiopharmaceuticals for therapy, and to optimise current treatment protocols, and to 2) enhance the understanding of mechanisms behind effects of ionising radiation both on tumour and normal tissues in vivo.

Some of the specific aims are:

1. to optimise treatment with radiolabelled hormone analogues for hormone receptor-expressing tumours.
2. to define possible biomarkers for radiotoxicity in tumour and normal tissues.
3. to optimise radionuclide therapy using enhanced understanding of basal molecular mechanisms behind radiobiological effects on tumour tissue and critical normal tissues.
4. to enhance the knowledge on radiation dosimetry and tolerance doses for radionuclide therapy in critical normal tissues.
5. to develop multi-parametric MRI for non-invasive evaluation of tumour tissue characteristics after radionuclide therapy.

Much research is focussed on the radiolabelled somatostatin analogue 177Lu-octreotate and the norepinephrine analogue 131I-MIBG for therapy of neuroendocrine tumours.

Currently, we examine ways to increase the radiobiological effects on tumour tissue by optimal fractionation schedules, new administration routes, increasing the receptor expression, reducing receptor saturation, combination with other agents (radiosenstizing).

We also examine ways to reduce the side effects on critical normal tissues, e.g by reducing kidney uptake and kidney toxicity. Furthermore, we suggest and validate biomarkers for radiobiological effects (toxicity) on tumour and normal tissues.

Research tools and resources

We perform translational studies on cell culture, mice, rats and patients. Pharmacokinetic and dosimetric studies are performed in tumour-bearing animals and man. Studies on toxicity and biological effects utilizes e.g imaging techniques (scintigraphy, MRI), histopathology, PCR and blotting techniques, microarray techniques, sequensing techniques, epigenetic analyses.

Current group members

Eva Forssell-Aronsson, PhD, Professor
Maria Ljungberg, PhD, Associate Professor
Emman Shubbar, PhD, Researcher
Johan Spetz, PhD, Researcher
Klara Insulander Björk, PhD, Researcher
Martin Andersson, PhD, Researcher
Mikael Montelius, PhD, Research engineer
Oscar Jalnefjord, PhD, Postdoc
Wendy Soria, PhD, Postdoc
Anja Schroff, PhD student
Hana Bakr, PhD student
Ingun Ståhl, PhD student
Louise Rosenqvist, PhD Student
Lukas Lundholm, PhD student
Mikael Elvborn, PhD student
Nishte Rassol, PhD Student
Jasmina Silnovic, Associate Researcher
Julia Johansson, Associate Researcher
Torgny Lundberg, Associate Researcher

The Forssell-Aronsson Lab is also part of Sahlgrenska Translational Neuroendocrine Cancer Group (SATNEC).

Selected publications

1. Local treatment of liver metastases by administration of 177Lu-octreotate via isolated hepatic perfusion – a preclinical simulation of a novel treatment strategy.
   Sandblom V, Ståhl I, Hansson C, Olofsson Bagge R, Forssell-Aronsson E.  Surgical Oncol, Jun 29: 148-156, 2019.
    
2. rA1M is a potential kidney protector in ¹⁷⁷Lu-octreotate treatment of neuroendocrine tumors.
   Andersson C, Shubbar E, Schüler E, Åkerström B, Gram M, Forssell-Aronsson E. J Nucl Med, 2019 Mar 29, [Epub ahead of print] 2019.
    
3. Transcriptional effects of ¹⁷⁷Lu-octreotate therapy using a priming treatment schedule on GOT1 tumor in nude mice.
   Spetz J, Langen B, Rudqvist N, Parris TZ, Dalmo J, Wängberg B, Nilsson O, Helou K, Forssell-Aronsson E. EJNMMI Res, 9(28): 1-11, 2019.
    
4. Multi-parametric MR for non-invasive evaluation of tumour tissue histological characteristics after radionuclide therapy.
   Montelius M, Spetz J, Nilsson O, Forssell-Aronsson E, Ljungberg M.  NMR Biomed, e4060, 2019. DOI: 10.1002/nbm.4060.
    
5. Hedgehog inhibitor sonidegib potentiates ¹⁷⁷Lu-octreotate therapy of GOT1 human small intestine neuroendocrine tumors in nude mice.
   Spetz J, Langen B, Rudqvist N, Parris TZ, Helou K, Nilsson O, Forssell-Aronsson E.  BMC Cancer, 17(1):528, 2017.
    
6. Priming increases the anti-tumor effect and therapeutic window of ¹⁷⁷Lu-octreotate in nude mice bearing human small intestine-neuroendocrine tumor GOT1.
   Dalmo J, Spetz J, Montelius M, Langen B, Arvidsson Y, Johansson H, Parris T, Helou K, Wängberg B, Nilsson O, Ljungberg M, Forssell-Aronsson E.  EJNMMI Res, 7(1):6, 2017.
    
7. Microarray studies on 211At administration in BALB/c nude mice indicate systemic effects on transcriptional regulation in non-thyroid tissues.
   Langen B, Rudqvist N, Helou K, Forssell-Aronsson E.  J Nucl Med, 58(2):346-353, 2017. PMID: 27765860.
    
8. Non-targeted transcriptomic effects upon thyroid irradiation: similarity between in-field and out-of-field responses varies with tissue type.
   Langen B, Rudqvist N, Spetz J, Swanpalmer J, Helou K, Forssell-Aronsson E.  Sci Rep, Oct 25;6:30738, 2016.
    
9. Estimation of absorbed dose to the kidneys in patients with neuroendocrine tumours after treatment with 177Lu-octreotate.
   Larsson M, Bernhardt P, Svensson J, Ahlman H, Wängberg B, Forssell-Aronsson E.  Eur J Nucl Med Mol Biol Res, 2(1): 49, 2012.
    
10. [177Lu-DOTA0-Tyr3]-octreotate treatment in patients with disseminated gastoenteropancreatic neuroendocrine tumours - the value of measuring absorbed dose to the kidney.
    Swärd C, Bernhardt P, Ahlman H, Wängberg B, Forssell-Aronsson E, Larsson M, Svensson J, Rossi-Norrlund R, Kölby L.  World J Surgery, 34(6): 1368-1372, 2010.

Group Forssell-Aronsson publications on PubMed