ABOUT THE RESEARCHER

OVERVIEW

Jason Dearling’s research focuses on the use of biomolecules to detect, describe and treat tissue disease.  New imaging probes, therapy agents and regimes developed by Dr. Dearling are now in clinical use.

Dr. Dearling’s current focus is to develop new detection and treatment approaches for cancer metastases.  Specifically, he is working on the radiolabeling and preclinical evaluation of antibodies that bind to neuroblastoma cells.  This will enable the quantification and characterization of neuroblastoma tumors through medical imaging (PET/CT) to guide treatment, and he is working with colleagues at St. Jude Children’s Research Hospital to take this approach into the clinic.

In addition to this core project, he is involved in a number of other disease areas, including:

  • Working with colleagues at Dana-Farber Cancer Institute to develop a new approach for the detection and therapy of Ewing’s Sarcoma. 
  • Through the development of new proteins, peptides and targeted liposomes, he is developing a theranostic approach to detect and quantify colitis, and to treat it with siRNA. 
  • The early detection of tissue rejection is crucial in the clinical decision making that follows cardiac transplant, and he is working with colleagues at BCH to develop new ways of detecting transplant blood flow, vascularization, immune cell invasion and rejection.

Due to the wide applicability of the work in his laboratory, Dr. Dearling also acts as a consultant to the biomedical community through the imaging core, “Imogen”.  This core provides a mechanism for probe and model development, imaging, and data analysis.

 

BACKGROUND

Jason Dearling received his PhD degree from the University of Kent.  He studied the structure-activity relationship between small molecules and their whole-body and intratumoral distribution, leading to the hypoxia tracer Cu-ATSM.  He then studied tumor biology with Professors R. Barbara Pedley and Richard Begent at University College London with the specific aim of quantifying the effect of the tumor microenvironment on targeted radiation therapy of colorectal cancer.  This work led to combination therapies that are now in clinical trials.  He then moved to Boston to work with Drs. Alan Packard and Stephan Voss at Harvard Medical School and Boston Children’s Hospital on another highly therapy-resistant cancer, neuroblastoma, where his objective is to develop an individualized approach to treating these patients by preventing the growth of metastases that arise after initial therapy.

Selected Publications

  1. Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe, in subcutaneous and orthotopic tumors. Dearling JL, Barnes JW, Panigrahy D, Zimmerman RE, Fahey F, Treves ST, Morrison MS, Kieran MW, Packard AB. Nucl Med Biol. 2013 Aug;40(6):788-94. 
  2. Detection of intestinal inflammation by MicroPET imaging using a (64)Cu-labeled anti-beta(7) integrin antibody. Dearling JL, Park EJ, Dunning P, Baker A, Fahey F, Treves ST, Soriano SG, Shimaoka M, Packard AB, Peer D. Inflamm Bowel Dis. 2010 Sep;16(9):1458-66. 
  3. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake. Dearling JL, Flynn AA, Qureshi U, Whiting S, Boxer GM, Green A, Begent RH, Pedley RB. Nucl Med Biol. 2009 Nov;36(8):883-94. 
  4. Combining radioimmunotherapy with antihypoxia therapy 2-deoxy-D-glucose results in reduction of therapeutic efficacy. Dearling JL, Qureshi U, Begent RH, Pedley RB. Clin Cancer Res. 2007 Mar 15;13(6):1903-10.
  5. Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. Dearling JL, Flynn AA, Sutcliffe-Goulden J, Petrie IA, Boden R, Green AJ, Boxer GM, Begent RH, Pedley RB. J Nucl Med. 2004 Jan;45(1):101-7.
  6. Copper bis(thiosemicarbazone) complexes as hypoxia imaging agents: structure-activity relationships. Dearling JL, Lewis JS, Mullen GE, Welch MJ, Blower PJ. J Biol Inorg Chem. 2002 Mar;7(3):249-59.

PUBLICATIONS

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  1. Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics. Nat Nanotechnol. 2021 09; 16(9):1030-1038. View abstract
  2. Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases. EJNMMI Res. 2021 Feb 25; 11(1):20. View abstract
  3. In vivo detection of antigen-specific CD8+ T cells by immuno-positron emission tomography. Nat Methods. 2020 10; 17(10):1025-1032. View abstract
  4. Positron Emission Tomography Detects In Vivo Expression of Disialoganglioside GD2 in Mouse Models of Primary and Metastatic Osteosarcoma. Cancer Res. 2019 06 15; 79(12):3112-3124. View abstract
  5. Molecular imaging in nanomedicine - A developmental tool and a clinical necessity. J Control Release. 2017 09 10; 261:23-30. View abstract
  6. A Sensitive Method for the Measurement of Copper at Trace Levels Using an HPLC-Based Assay. Curr Radiopharm. 2017; 10(1):59-64. View abstract
  7. Colitis ImmunoPET: Defining Target Cell Populations and Optimizing Pharmacokinetics. Inflamm Bowel Dis. 2016 Mar; 22(3):529-38. View abstract
  8. Use of [18F]FDG Positron Emission Tomography to Monitor the Development of Cardiac Allograft Rejection. Transplantation. 2015 Sep; 99(9):e132-9. View abstract
  9. The ionic charge of copper-64 complexes conjugated to an engineered antibody affects biodistribution. Bioconjug Chem. 2015 Apr 15; 26(4):707-17. View abstract
  10. On the destiny of (copper) species. J Nucl Med. 2014 Jan; 55(1):7-8. View abstract
  11. Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody. Clin Cancer Res. 2014 Feb 01; 20(3):678-87. View abstract
  12. Specific uptake of 99mTc-NC100692, an avß3-targeted imaging probe, in subcutaneous and orthotopic tumors. Nucl Med Biol. 2013 Aug; 40(6):788-94. View abstract
  13. 64Cu-p-NH2-Bn-DOTA-hu14.18K322A, a PET radiotracer targeting neuroblastoma and melanoma. J Nucl Med. 2012 Nov; 53(11):1772-8. View abstract
  14. PET-radioimmunodetection of integrins: imaging acute colitis using a 64Cu-labeled anti-ß7 integrin antibody. Methods Mol Biol. 2012; 757:487-96. View abstract
  15. Radioimmunotherapy: optimizing delivery to solid tumors. Ther Deliv. 2011 May; 2(5):567-72. View abstract
  16. Imaging cancer using PET--the effect of the bifunctional chelator on the biodistribution of a (64)Cu-labeled antibody. Nucl Med Biol. 2011 Jan; 38(1):29-38. View abstract
  17. Detection of intestinal inflammation by MicroPET imaging using a (64)Cu-labeled anti-beta(7) integrin antibody. Inflamm Bowel Dis. 2010 Sep; 16(9):1458-66. View abstract
  18. Some thoughts on the mechanism of cellular trapping of Cu(II)-ATSM. Nucl Med Biol. 2010 Apr; 37(3):237-43. View abstract
  19. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake. Nucl Med Biol. 2009 Nov; 36(8):883-94. View abstract
  20. Fractionated 131I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice. Br J Cancer. 2008 Aug 19; 99(4):632-8. View abstract
  21. Microdistribution of targeted, fluorescently labeled anti-carcinoembryonic antigen antibody in metastatic colorectal cancer: implications for radioimmunotherapy. Clin Cancer Res. 2008 May 01; 14(9):2639-46. View abstract
  22. Predicting response to radioimmunotherapy from the tumor microenvironment of colorectal carcinomas. Cancer Res. 2007 Dec 15; 67(24):11896-905. View abstract
  23. Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates. Proc Natl Acad Sci U S A. 2007 Oct 30; 104(44):17489-93. View abstract
  24. Technological advances in radioimmunotherapy. Clin Oncol (R Coll Radiol). 2007 Aug; 19(6):457-69. View abstract
  25. Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models. Br J Cancer. 2007 Jun 18; 96(12):1862-70. View abstract
  26. Combining radioimmunotherapy with antihypoxia therapy 2-deoxy-D-glucose results in reduction of therapeutic efficacy. Clin Cancer Res. 2007 Mar 15; 13(6):1903-10. View abstract
  27. Combretastatin A-4-phosphate effectively increases tumor retention of the therapeutic antibody, 131I-A5B7, even at doses that are sub-optimal for vascular shut-down. Int J Oncol. 2007 Feb; 30(2):453-60. View abstract
  28. Tumour parameters affected by combretastatin A-4 phosphate therapy in a human colorectal xenograft model in nude mice. Eur J Cancer. 2005 Mar; 41(5):799-806. View abstract
  29. Nonuniform absorbed dose distribution in the kidney: the influence of organ architecture. Cancer Biother Radiopharm. 2004 Jun; 19(3):371-7. View abstract
  30. Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. J Nucl Med. 2004 Jan; 45(1):101-7. View abstract
  31. Higher dose and dose-rate in smaller tumors result in improved tumor control. Cancer Invest. 2003 Jun; 21(3):382-8. View abstract
  32. The nonuniformity of antibody distribution in the kidney and its influence on dosimetry. Radiat Res. 2003 Feb; 159(2):182-9. View abstract
  33. Synergy between vascular targeting agents and antibody-directed therapy. Int J Radiat Oncol Biol Phys. 2002 Dec 01; 54(5):1524-31. View abstract
  34. Spatial accuracy of 3D reconstructed radioluminographs of serial tissue sections and resultant absorbed dose estimates. Phys Med Biol. 2002 Oct 21; 47(20):3651-61. View abstract
  35. Dissociation of glucose tracer uptake and glucose transporter distribution in the regionally ischaemic isolated rat heart: application of a new autoradiographic technique. Eur J Nucl Med Mol Imaging. 2002 Oct; 29(10):1334-41. View abstract
  36. A model-based approach for the optimization of radioimmunotherapy through antibody design and radionuclide selection. Cancer. 2002 Feb 15; 94(4 Suppl):1249-57. View abstract
  37. Copper bis(thiosemicarbazone) complexes as hypoxia imaging agents: structure-activity relationships. J Biol Inorg Chem. 2002 Mar; 7(3):249-59. View abstract
  38. Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate. Cancer Res. 2001 Jun 15; 61(12):4716-22. View abstract
  39. Effectiveness of radiolabelled antibodies for radio-immunotherapy in a colorectal xenograft model: a comparative study using the linear--quadratic formulation. Int J Radiat Biol. 2001 Apr; 77(4):507-17. View abstract
  40. Copper bis(diphosphine) complexes: radiopharmaceuticals for the detection of multi-drug resistance in tumours by PET. Eur J Nucl Med. 2000 Jun; 27(6):638-46. View abstract
  41. Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro. Eur J Nucl Med. 1998 Jul; 25(7):788-92. View abstract