Study of the kinetics of complex formation and in vivo stability of novel radiometal-chelate conjugates for applications in nuclear medicine Monika Stachura.

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Presentation transcript:

Study of the kinetics of complex formation and in vivo stability of novel radiometal-chelate conjugates for applications in nuclear medicine Monika Stachura on behalf of the P501 collaboration

IS501 Collaboration Valery Radchenko, Monika Stachura, Caterina Ramogida, Paul Schaffer, Cornelia Hoehr Lars Hemmingsen, Peter W. Thulstrup, Morten J. Bjerrum Ulli Koester Chris Orvig Karl Johnston, Juliana Schell Dmitry Filosofov, Elena Kurakina Doru C. Lupascul

Radiopharmaceuticals Chelator Biomolecule Radionuclide Specific target

Targeted Radionuclide Therapy (TRT) Candidates: Targeted Alpha Therapy: 212Pb (t1/2 10.64 h) Targeted Auger Therapy: 119Sb (t1/2 38.5 h) 197gHg (t1/2 64.14 h) Challenges: Design of appropriate chelation systems Kinetics of complex formation (gram) Radionuclide complex stability in vivo Pouget J.-P. et al. (2011) Clinical radioimmunotherapy—the role of radiobiology Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2011.160

PAC Spectroscopy PAC spectroscopy: Studies of radiometal-complex structure in vitro and in vivo Kinetics of complex formation (mg of ligand) Studies of complex stability in vitro and in vivo Direct studies under biologically relevant conditions PAC spectroscopy: Targeted Alpha Therapy: 212Pb (t1/2 10.64 h) → PAC isotope 204mPb Targeted Auger Therapy: 119Sb (t1/2 38.5 h) → PAC isotope 118mSb 197gHg (t1/2 64.14 h) → PAC isotope 199mHg

PAC Measurements Step I: Experiments with well-known (commercially available) complexes Step II: Experiments with novel complexes Synthesised at UBC/TRIUMF Hg

In vivo Generators In vivo generators: Generator: mother radionuclide decays to the daughter radionuclide (suitable for imaging or therapy) Challenge: keeping stable complex during transition between parent and daughter Unknown: will the daughter remain attached to the targeting complex? Possible in vivo generators: Imaging: 44mSc/44gSc,140Nd/140Pr, 134Ce/134La, 52Fe/52mMn, 62Zn/62Cu Therapy: 212Pb/212Bi, 166Dy/166Ho, 225Ac/213Bi

In vivo Generators PAC isotopes: 139mNd/139Pr, 140La/140Ce, 147Gd/147Eu, 149Gd/149Eu, 151Tb/151Gd, 172Lu/172Yb Step I: Experiments with well-known (commercially available) complexes Step II: Comparison of β- decays (i.e. La>Ce) with EC decays (i.e. Lu>Yb) where the nuclear charge of the daughter nuclide increases or decreases, respectively.

PAC Experiments at ISOLDE Step I: Collections GLM / new biophysics chamber Implantations into foils and ice Step II: Chemistry Sample preparation in the Chemistry lab (b.508) Short-lived isotopes → measurements performed immediately Long-lived isotopes → measurements performed later (or shipped elsewhere) Step III: PAC measurements PAC spectrometers in b. 508 (PAC lab)

Total: 15 shifts over 2 years, several runs Beam Request Total: 15 shifts over 2 years, several runs

Long-lived contamination: 139Ce (139d) Beam Request New biophysics chamber (designed by M. da Silva, in production, ready in 6 weeks) Long-lived contamination: 139Ce (139d)

IS501 Outputs 2012-2017 24 PhD theses 5 MSc theses 159 peer-reviewed publications 101 oral presentations at the international conferences

Thank you! Merci! Follow us at TRIUMFLab