21 January 2019

In preclinical prostate carcinoma in the bone, Rad-223 eradicated effectively micro-tumors but macro-tumors persisted and expanded. The data point to application of Rad-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the tumor core.

Peter Friedl, theme Cancer development and immune defense, and colleagues, published these findings in the Journal of the National Cancer Institute (JNCI).

Bone-targeting radiotherapy with Radium-223 (Rad-223), a radioisotope emitting genotoxic alpha-radiation with limited tissue penetrance (∼100 µm), prolongs the survival of patients with metastatic prostate cancer (PCa). Confoundingly, the clinical response to Rad-223 is often followed by detrimental relapse and progression, and whether Radium-223 causes tumor-cell directed cytotoxicity in vivo remains unclear. In a joint effort between the Radboudumc and the MD Anderson Cancer Center, they show that limited radiation penetrance in situ defines outcome. 
 
They tested the Radium-223 overall response in prostace cancer in mouse bones and applied intravital microscopy and in silico modeling to predict Rad-223 effectiveness in lesions of different sizes. Rad-223 caused profound cancer cell lethality along the bone interface but not the more distant tumor core. In silico simulations predicted greater efficacy of Rad-223 on single-cell lesions (eradication rate: 88.0%) and minimal effects on larger tumors (no eradication, 16.2% growth reduction in tumors of 27,306 cells), further confirmed in vivo tumors in mice. Micro-tumors showed severe growth delay or eradication in response to Rad-223, whereas macro-tumors persisted and expanded. 
 
The relative inefficacy in controlling large tumors points to application of Rad-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the bone niche together with the tumor core.

Related news items


Retirement of Huib Croes

12 September 2019

After a long working life of 35 years at the Department of Cell Biology, now a well-deserved retirement. Thank you Huib Croes!

read more

VSB Scholarships for studying or performing research abroad

12 September 2019

For students who have finished or will finish their BSc or MSc between 1-3-2019 and 31-12-2020.

read more

A personal touch of Laura Diepeveen

12 September 2019

In order to promote interaction amongst colleagues within RIMLS, we have a ‘personal touch’ series setting employees in the spotlight. A light-hearted manner to learn about the colleagues you know and those you don’t. This week: Laura Diepeveen.

read more

'Radboudpluim' for Jeanette Pots

12 September 2019

Jeanette Pots received the 'Radboudpluim' from Paul Smits, for her exceptional services as technician at the departement of Tumor Immunology.

read more

RIMLS PhD grants awarded to eight RIMLS (j)PI's

12 September 2019

Recently, RIMLS held an internal call for Radboudumc junior researcher (PhD) positions. Congratulations for all the awardees and all the best in conducting the research projects.

read more

'Radboudpluim' for Nathalie Bovy-Van der Lugt

6 September 2019

Nathalie Bovy- Van der Lugt received the 'Radboudpluim' from Paul Smits, for her exceptional services as policy advisor for the Donders Centre of Medical Neuroscience and Radboudumc.

read more