Subprogram 5

Testing the therapeutic and diagnostic potential of molecular and supramolecular carriers in vivo

The in vivo evaluation will be mainly carried out by two partners, Nuclear Medicine (ERASMUS MC) and MILabs. On the therapeutic side ERASMUS MC will examine the potential of radiolabelled molecular and supramolecular carriers in the treatment of neuroendocrine tumours in preclinical models as well as in neuroendocrine tumor specimens from the clinic.

The preclinical research will further proceed by investigating the affinity of new targeted carriers using autoradiography on human and rat tumour sections (H69 and CA20948). In vivo stability of the carriers will be carried out by injection of the entities in mice. Subsequently, in-vivo imaging, biodistribution and radionuclide therapy studies in mice tumour model will be carried out to determine tumour uptake and anti-tumour effects after therapy of the most promising targeted and non-targeted radiolabelled carriers. In this study systemic radiotherapy using negatrons will be compared with therapy using alpha emitters. The Alpha-Immunotherapy group (ITU) will assist in radiolabelling with alpha emitters and in the preclinical trials.

The uptake of radiolabelled compounds is commonly assessed by bio-distribution studies in combination with ex vivo autoradiography. Such studies involve the sacrifice of series of animals at several time points. In our studies, we will use fast dynamic imaging studies starting at the time of drug injection to provide pharmacokinetic information. Additionally, monitoring of animals over a long period of time will simplify the assessment of therapy. This approach will also reduce the number of animals required.

The organization of the project requires the frequent use of imaging techniques in order to assess the imaging potential of all three categories of carriers equipped with different radiolabels. This time consuming task cannot be carried out solely by Nuclear Medicine in addition to their therapeutic assessment. MILabs, specializing in the development of small animal imaging techniques is the most suitable partner.

During this program the in vivo potential of radiolabelled molecular and supramolecular carriers will be evaluated.

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