Dive into Imaging Science

GUEST: John Ronald, London (ON, Canada)Welcome back!  It has been a while but are back with a bang, having our good friend John Ronald from The Robarts Research Institute in London, Ontario as our guest. John's group combines advances in molecular and synthetic biology with a multimodal imaging perspective to build new tools for early detection and treatment of cancer, as well as non-invasive monitoring of cell, gene and genome therapies. One of John's passions is gene reporter imaging, which is also the main focus of this edition. The paper up for discussion comes from Cynthia Dunbar's lab at NIH, Bethesda which was recently published in Cell Stem Cell. We discover their approach to non-invasively follow engraftment and maturation of pluripotent stem cells in rhesus macaques with myocardial infarctions, discuss some of the technicalities of engineering autologous cells, and fall in love with the beautiful RNAScope images that are presented. We discuss what makes a good imaging reporter, why one size doesn't always fit all, and a future where not just cells, but activation states can be imaged. Along the way, John also shares advices received from the wonderful Sanjiv Sam Gambhir on how to improve the chances of getting your grants funded and that supposedly crazy ideas should not be discarded... they might even lead to high impact publications.And of course, true to our tradition, we enjoy a special cocktail. For this edition the “Angry Canadian”, obviously. For the curious listeners: a good measure of Whisky, 2 tablespoons of fine Canadian Maple syrup, a few drops of bitters and 1 teaspoon lemon juice, then top up with soda water.Selected Publication: Lin Y, Sato N, Hong S, Nakamura K, Ferrante EA, Yu ZX, Chen MY, Nakamura DS, Yang X, Clevenger RR, Hunt TJ, Taylor JL, Jeffries KR, Keeran KJ, Neidig LE, Mehta A, Schwartzbeck R, Yu SJ, Kelly C, Navarengom K, Takeda K, Adler SS, Choyke PL, Zou J, Murry CE, Boehm M, Dunbar CE. Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques. Cell Stem Cell. 2024 Jul 5;31(7):974-988.e5. doi: 10.1016/j.stem.2024.05.005. Epub 2024 Jun 5. PMID: 38843830; PMCID: PMC11227404. https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00182-6Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu 

GUEST: Kevin Brindle, CambridgeIn this episode we welcome the one and only Kevin Brindle from University of Cambridge.During his long and illustrious career, Kevin pioneered hyperpolarized magnetic resonance spectroscopy as a method to map metabolic flux in cancer and other diseases, with implications for treatment response monitoring.We explore how deuterium imaging and [18F]FDG PET can be used to track the metabolic changes that occur soon after stroke and during the recovery phase. We discuss the complementary information that these two techniques provide and whether they could be used to improve clinical outcomes.Along the way, we learn how Kevin could have worked in structural biology or been a painter and decorator... and how he used to meet his wife-to-be in the cold room when he was a postdoc at Oxford.Selected Publication: In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging. Meerwaldt AE, Straathof M, Oosterveld W, van Heijningen CL, van Leent MM, Toner YC, Munitz J, Teunissen AJ, Daemen CC, van der Toorn A, van Vliet G, van Tilborg GA, De Feyter HM, de Graaf RA, Hol EM, Mulder WJ, Dijkhuizen RM. J Cereb Blood Flow Metab. 2023 May;43(5):778-790. doi: 10.1177/0271678X221148970. Epub 2023 Jan 6.https://journals.sagepub.com/doi/10.1177/0271678X221148970 Further information on the European Society for Molecular Imaging: https://e-smi.eu/ Contact: office@e-smi.eu 

GUEST: Mikhail Shapiro, PasadenaIn this episode we welcome our famous guest Mikhail Shapiro from Caltech. Mikhail exquisitely combines ultrasound with synthetic biology for gene regulation, imaging, and therapy - and Synthetic biology is surely the common thread in this podcast edition.We discover how an engineered receptor and an intracellular signalling domain, known as ‘synNotch' can be used to visualise cell-cell communication in vivo. And how this system can be used to identify immune-cancer cell interactions, why it provides far more information than just knowing where the immune cells reside, and the various merits of the three different reporter genes employed for visualisation across scales.We also reveal some insider information into the review process for the selected paper from the senior author John Ronald. Along the way, we speculate why the synNotch system improves NK cell kill and Tim ends up dreaming of sheep jumping over logic gates!Selected Publication: Visualizing cell–cell communication using synthetic notch activated MRI. TianDuo Wang, Yuanxin Chen, Nivin N Nystrom, Shirley Liu, Yanghao Fu, Francisco M Martinez, Timothy J Scholl, and John A Ronald. Proc Natl Acad Sci U S A. 2023 Mar 14; 120(11):e2216901120. doi: 10.1073/pnas.2216901120.https://www.pnas.org/doi/abs/10.1073/pnas.2216901120Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Jason Lewis, New YorkIn this episode we discuss and learn about new PSMA-binding ligands with 161Tb, their biodistribution, dosimetry, preclinical therapy, and their comparison with conventional PSMA ligands. Our guest is one of the leading scientists in radiochemistry for cancer detection and therapy, the wonderful Jason Lewis. We talk about the importance of using 161Tb - this novel radionuclide for radioligand therapy - and its favorable decay characteristics as compared to 177Lu. We learn about the added value of the emission of Auger electrons which can effectively eliminate micro-metastasis and when combined with ibuprofen-based PSMA ligands offering albumin-binding properties, tumor uptake and therapeutic efficacy are significantly boosted. Besides this fascinating science, don't miss some very important advice from a very successful scientist in a very competitive environment about work-life balance, prioritising expectations and goals - just never forget to "smell the roses"…Selected Publication: Albumin-Binding and Conventional PSMA Ligands in Combination with 161Tb: Biodistribution, Dosimetry, and Preclinical Therapy. Viviane J. Tschan, Sarah D. Busslinger, Peter Bernhardt, Pascal V. Grundler, Jan Rijn Zeevaart, Ulli Köster, Nicholas P. van der Meulen, Roger Schibli, Cristina Müller. Journal of Nuclear Medicine Jul 2023, jnumed.123.265524; DOI: 10.2967/jnumed.123.265524https://jnm.snmjournals.org/content/early/2023/07/13/jnumed.123.265524Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Annemie Van Der Linden, AntwerpIn this edition of ‘Dive into Imaging Science' we discuss the brain and the mechanisms that it employs to clear unwanted waste material whilst we sleep with our former ESMI President and Emeritus Professor Annemie Van Der Linden - an outstanding figure and incomparable scientist.We learn how closely coupled this system - known as the glymphatics - is to blood circulation, and how physical stimulation can enhance glymphatic flow in anaesthetised but not awake mice. Along the way, we learn how curiosity and a wondering mind has led Annemie to use a wide range of models to study the brain, from fish to song birds.Selected Publication: Glymphatic influx and clearance are accelerated by neurovascular coupling. Holstein-Rønsbo S, Gan Y, Giannetto MJ, Rasmussen MK, Sigurdsson B, Beinlich FRM, Rose L, Untiet V, Hablitz LM, Kelley DH, Nedergaard M. Nat Neurosci. 2023 Jun;26(6):1042-1053. doi: 10.1038/s41593-023-01327-2. Publication reference: Holstein-Rønsbo S, Gan Y, Giannetto MJ, Rasmussen MK, Sigurdsson B, Beinlich FRM, Rose L, Untiet V, Hablitz LM, Kelley DH, Nedergaard M. Glymphatic influx and clearance are accelerated by neurovascular coupling. Nat Neurosci. 2023 Jun;26(6):1042-1053. doi: 10.1038/s41593-023-01327-2. Epub 2023 Jun 1. PMID: 37264158. https://www.nature.com/articles/s41593-023-01327-2Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Elisabeth de Vries, GroningenIn this episode we talk about nectin-4 - an emerging biomarker for cancer diagnosis and therapy - with one of the most influential and distinguished scientists in medical oncology, Elisabeth de Vries. We talk about the first-in-human study of a radioligand that can target nectin-4 and learn what medical oncologists need to get out from imaging data so that these powerful tools continue to make an impact on patient outcomes. We learn about the importance and best practices for robust clinical trials and the hurdles to both design and finance them. Along the way, we get a glimpse into Elisabeth's career path and how her research combines nuclear with optical imaging modalities as methods to improve patient diagnosis and treatment.Selected Publication: "First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET/CT imaging of advanced urothelial carcinoma" published in Clinical Cancer research by the authors X. Duan, L. Xia, Z. Zhang, Y. Ren, M. G. Pomper, S. P. Rowe, X. Li, N. Li, N. Zhang, H. Zhu 6, Z. Yang, X. Sheng, X. Yang  (groups from Beijing University and Johns Hopkins University Baltimore).Publication reference: Xiaojiang Duan, Lei Xia, Zhuochen Zhang, Yanan Ren, Martin G Pomper, Steven P Rowe, Xuesong Li, Nan Li, Ning Zhang, Hua Zhu 6, Zhi Yang, Xinan Sheng, Xing Yang. First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET/CT imaging of advanced urothelial carcinoma. Clin Cancer Res. 2023 Apr 24;CCR-23-0609. doi: 10.1158/1078-0432.CCR-23-0609. https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-23-0609/726342/First-in-Human-Study-of-the-Radioligand-68Ga-N188Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Bernd Pichler, TübingenIn this episode we learn how a new lensless microscope, costing just $100 (!), can be used to evaluate radiotracer retention in cells, and discuss potential applications for this revolutionary new technology with our famous guest Bernd Pichler. We discuss how this, and other technologies, could be used to assess the heterogeneous cell populations of the tumour microenvironment and identify cell senescence using new radiotracers developed in Bernd's lab.Selected Publication: "Development of a Lensless Radiomicroscope for Cellular-Resolution Radionuclide Imaging" published in Journal of Nuclear Medicine by the authors Justin S. Klein, Tae Jin Kim and Guillem Pratx (Physical Oncology Lab at Stanford  Medicine).Publication reference: Justin S. Klein, Tae Jin Kim and Guillem Pratx. Development of a Lensless Radiomicroscope for Cellular-Resolution Radionuclide Imaging. J Nucl Med 2023 Mar; 64(3):479-484. doi: 10.2967/jnumed.122.264021. Epub 2022 Sep 15.https://jnm.snmjournals.org/content/64/3/479Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Zaver Bhujwalla, BaltimoreIn this episode we discuss how targeting fibroblasts rather than tumour cells may be an effective strategy for both surgical guided resection and as an anti-cancer therapy with Tim's “academic grandmother”, Zaver Bhujwalla. We discovered Zaver's roots as a physicist and mathematician, learned about her (unpredictable) interest in cancer metabolism and how she combines tools to develop a powerful in vitro diagnostic test.Selected Publication: "Design and characterization of fibroblast activation protein targeted pan-cancer imaging agent for fluorescence-guided surgery of solid tumors" published in Journal of Materials Chemistry B, by the the authors Mukkamala R, Lindeman SD, Kragness KA, Shahriar I, Srinivasarao M, Low PS (Purdue University, West Lafayette, USA).Publication reference: Mukkamala R, Lindeman SD, Kragness KA, Shahriar I, Srinivasarao M, Low PS. Design and characterization of fibroblast activation protein targeted pan-cancer imaging agent for fluorescence-guided surgery of solid tumors. J Mater Chem B. 2022 Mar 23;10(12):2038-2046. doi: 10.1039/d1tb02651h.https://pubs.rsc.org/en/content/articlelanding/2022/TB/D1TB02651HFurther information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Clemens C.W.G. Lowik, RotterdamIn this episode we discuss and learn about Bioluminescence Imaging and modern tools for multiplexed imaging of different colors, tackling a major challenge of the field. Our guest is one of the founding fathers of the ESMI and pioneers on multicolor BLI, the one and only  Clemens Lowik. We talk about innovative approaches for unmixing multiple luciferase-luciferin pairs and quantitative analyses of bioluminescent mixtures, enabling serial tracking of heterogeneous cell populations. On the course of our discussion we learn on how such methods will help advance BLI to cover new exciting regimes, but also spill over to the wider optical imaging. If you're on to exciting developments of the field - listen carefully!Selected Publication: "Multiplexed bioluminescence imaging with a substrate unmixing platform" published in Cell Chemical Biology by the authors C. K. Brennan, Z. Yao, A.A. Ionkina, C.M. Rathbun, B. Sathishkumar, J.A. Prescher (University of California, Irvine, USA).Publication reference: C. K. Brennan, Z. Yao, A.A. Ionkina, C.M. Rathbun, B. Sathishkumar, J.A. Prescher. Multiplexed bioluminescence imaging with a substrate unmixing platform. Cell Chem Biol. 2022 Nov 17;29(11):1649-1660.e4. doi: 10.1016/j.chembiol.2022.10.004. Epub 2022 Oct 24 .https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(22)00358-0Further information on the European Society for Molecular Imaging:https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Simon Cherry, UC DavisIn this episode we discuss (and learn a lot about!) positronium imaging with the co-inventor of Total Body PET, the wonderful Simon Cherry, the physics behind positronium formation, and how it might provide further biological information than standard positron emission tomography imaging. We learnt about Simon's journey that led him to change the field of clinical PET imaging and what new innovations he has up his sleeve... and if you are looking for a research area that is just waiting to be explored - listen carefully! Selected Publication: "Positronium imaging with the novel multiphoton PET scanner" published in Science Advances by the the authors P Moskal, K Dulski, N Chug, C Curceanu, E Czerwiński, M Dadgar, +30, and W. Wislicki (Kraków, Poland).Publication reference: P Moskal, K Dulski, N Chug, C Curceanu, E Czerwiński, M Dadgar, +30, and W. Wislicki. Positronium imaging with the novel multiphoton PET scanner. Sci Adv 2021 Oct 15;7(42):eabh4394. doi: 10.1126/sciadv.abh4394. Epub 2021 Oct 13.https://www.science.org/doi/full/10.1126/sciadv.abh4394Further information on the European Society for Molecular Imaging: https://e-smi.eu/Contact: office@e-smi.eu

GUEST: Jolanda de Vries, NijmegenIn this episode the hosts Tim and Giannis talk with the fantastic Jolanda De Vries from Nijmegen about how dendritic cell therapy got her into imaging and the latest therapeutic cell imaging methods. We touch on multimodality imaging, why imaging isn't frequently used in the clinic for cell tracking, and why mouse models of cancer might never be good enough.Selected Publication: "In vivo imaging of nanoparticle-labeled CAR T cells" published in Proceedings of the National Academy of Sciences (PNAS) by the authors L. Kiru, A. Zlitni, A. Michael +9, and H. E. Daldrup-Link (Pediatric Molecular Imaging Lab at Stanford Medicine).Publication reference: Kiru L, Zlitni A, Tousley AM, Dalton GN, Wu W, Lafortune F, Liu A, Cunanan KM, Nejadnik H, Sulchek T, Moseley ME, Majzner RG, Daldrup-Link HE. In vivo imaging of nanoparticle-labeled CAR T cells. Proc Natl Acad Sci U S A. 2022 Feb 8;119(6):e2102363119 https://www.pnas.org/doi/full/10.1073/pnas.2102363119Further information on the European Society for Molecular Imaging: https://e-smi.eu/Contact: office@e-smi.eu