In this project we develop novel radiopharmaceuticals, which can participate in bioorthogonal reactions in vivo. Bioorthogonal reactions are based on small, abiotic and bioinert functional groups, which can react chemoselectively in the multiform environment of biological systems surrounded with innumerable amount of different biofunctionalities. These bioorthogonal radiopharmaceuticals are applied for tracing targeted therapeutic nanoparticles in a body by PET and SPECT. The developed methodology allows use of short living positron and gamma-emitting radioisotopes in nanotheranostic applications without causing unnecessary radiation burden to the patient. The methodology allows longitudinal studies on nanomaterial distribution and is aimed to facilitate translation of nanotheranostic anticancer therapies into clinics. Also other systems with slow pharmacokinetics are under investigation, such as antibodies. The research is carried out in national and international collaboration with research groups working with materials science, cancer research, and imaging. (PI Anu Airaksinen)

Pretargeting of PSi nanoparticles in vivo with a 18F-tetrazine radiotracer

KIT Ra­diola­beling of bio­molecules with flu­or­ine-18

In this project we develop new radiochemistry for production of radiopharmaceuticals for positron emission tomography (PET). In the project new 18F-fluorination reagents will be developed. These reagents are aimed to allow utilization of simple mix-and-use approaches for production of biomolecular PET radiopharmaceuticals, such as radiopharmaceuticals made from peptides, peptidomimetics or antibody fragments. (PI Anu Airaksinen)

NEW tracers for ion chan­nels in the peri­pheral nervous sys­tem

The pharmacology of ion channels in the peripheral nervous system (PNS) is an emerging topic in neuroscience lacking effective molecular imaging tools to date. For example, the upregulation of TRPV1 (Transient Receptor Potential Vanilloid 1) PNS has recently been implicated in many pathologic conditions including visceral hypersensitivity in Irritable Bowel Disease (IBD) and colitis, chronic neuropathic pain, and cancer bone metastasis. Similarly, the involvement of many voltage-gated ion channels in these conditions remains understudied in the lack of suitable tracers. The aim of this project is to develop new fluorescent and PET molecular imaging probes based on natural channel ligand leads for TRPV1 and voltage-gated ion channels employing various click and coupling chemistries and to evaluate the developed tracers in cell and animal models of PNS disorders. (PI Mirkka Sarparanta)

por­ous sil­icon (PSI) and LIPID nan­o­ma­ter­i­als

In this project new radiotracer methods are developed for tracing targeted therapeutic nanoparticles by sensitive and clinically relevant in vivo imaging modalities, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The developed methods enable combining therapy and diagnostics to the same nanomaterial to so called nanotheranostics. In collaboration with several research groups working on material science and drug delivery, we have investigated in vivo properties of several new nanomaterials as potential new drug delivery agents, such as lipid based nanomaterials (e.g. non-lamellar liquid crystalline hexosomes), and porous silicon nanoparticles (PSi) with different surface modifications. For tracing PSi nanoparticles in vivo we have developed a direct 18F-labeling method for thermally passivated silicon surface, which have allowed quantitative assessment of PSi distribution in a body after different administration routes (intravenous, subcutaneous and oral) for the first time. The method has been extremely valuable in studying influence of several different surface modifications on PSi distribution and fate in vivo (e.g. hydrophobin II, solid lipids and targeting peptides). In order to be able to follow particle distribution for longer time we have developed methods for labeling the PSi particles with 111In (t1/2 = 2.8 d). Sorafenib loaded 111In-labeled PSi particles were used in a survival study for investigating correlation between tumor accumulation/retention of the PSi NPs and their efficacy in inhibiting tumoral growth after intravenous and intratumoral administration in prostate tumor xenografts. We have used 111In-labeled PSi particles also for evaluation of efficiency of atrial natriuretic peptide (ANP) to target PSi into ischemic myocardium.  The gained understanding on PSi in vivo behaviour achieved so far, have been crucial in development of porous silicon nanomaterials towards their biomedical applications. (PI Anu Airaksinen)


Strategies for the use of molecular imaging for the evaluation of nanoscale drug delivery systems

Mul­timod­al­ity ima­ging tools BASED ON nano­cel­lu­lose and lignin

The aim of the project is to develop new multimodality labeling methods for nanocellulose and lignin biomaterials in order to investigate their potential for systemic and oral drug delivery and as scaffolds for the development of multimodality imaging probes for intraoperative and endoscopic imaging of the digetive system. CNC and lignin nanoparticles prepared from renewable sources are emerging nanomaterials for biomedical applications. CNC has many unique properties including facile and cost-effective preparation via selective acid hydrolysis of amorphous regions in the biopolymer, biocompatible OH-termination, and versatile chemistry through functionalization of the surface OH-groups. CNC can be prepared from a number of natural sources including wood pulp, bamboo, cotton, and tunicate mantles, and depending on the source and route of preparation, the material dimensions and properties can be tuned at a wide range to give both small, rigid nanocrystals, and longer flexible nanofibres (both can be grouped under the term nanocellulose). Lignin, a highly aromatic polymer of p-coumaryl, coniferyl, and sinapyl alcohols is less studied for biomedical applications, but allows the facile preparation of uniform, spherical and stable nanoparticle dispersions. As for CNC, the surface chemistry of lignin is extremely versatile allowing for the conjugation of a number of functional groups and hydrophobic compounds. To date, biomedical applications of CNC and lignin have been limited to use as an excipient in drug formulations, and as a reinforcing component in scaffolds for tissue engineering, and our research will help drive the development of CNC and lignin materials for systemic delivery.  (PI Mirkka Sarparanta)

Development of multimodal CNC imaging probes


Metal im­planted multi-func­tional nan­ovectors for tar­geted ra­dio­ther­apy and dia­gnostics

The study of porous nanoparticles as drug carriers is a growing field in cancer therapy research.  The aim of our project is to develop methods to produce radioactive-ion implanted porous silicon nanoparticles (PSi) for therapeutic and diagnostic applications of cancer.  This can be realized using different methods like proton or neutron irradiation of PSi particles that have been doped with suitable stable ions.  Another approach is the direct implantation of radioactive ions in the particles.  The resulting radioactive nanoparticles are further modified with tumor targeting moieties and loaded with anticancer drugs, enabling tumor specific chemoradiotherapy of cancer. PSi has an extraordinary high drug loading capacity, which allows the delivery of therapeutically relevant doses into the tumor tissue without using impractically high amount of the nanoparticles. By selecting therapeutic radionuclides which are amenable for nuclear imaging, trafficking of the administered chemoradiotherapy nanovectors is followed by non-invasive imaging whether with single emission computed tomography (SPECT) or positron emission tomography (PET). (PI Kerttuli Helariutta)


RanoRad project scheme

The research in the TRIM group is currently funded by the Academy of Finland, the University of Helsinki, and a number of Finnish foundations, the contributions of all financial supporters to ensuring the continuation of our research is gratefully acknowledged. For more information on research funding, please use the search tools provided at the websites of the funding agencies.

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