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Radiology Research

Research Overview

Alan Packard is the Director of the Radiopharmaceutical Research Laboratory at BCH.  The two primary goals of his research are the development and preclinical evaluation of 1) radiometal-based PET (positron emission tomography) imaging agents and therapeutics and 2) 18F-labeled compounds for the PET imaging of heart disease and neurological disorders. 

The principal objectives of the radiometal projects are the imaging and therapy of neuroblastoma, the most common extracranial solid tumor diagnosed in children, and inflammatory bowel disease, a common condition for which there are currently no non-invasive options for the evaluation of disease status.  Both of these projects employ antibodies radiolabeled with 64Cu or 89Zr for imaging while 177Lu is employed as the radiolabel for the therapeutic arm of the neuroblastoma project.  An important component of the radiometal projects is the more complete elucidation of the chemical properties of the complexes formed by the radiometals with the bifunctional chelators used to attach them to proteins.

The primary 18F project is the development of a new radiopharmaceutical for evaluating myocardial perfusion with PET.  The prototype compound is derived from a rhodamine dye, and preclinical studies show that it has high uptake in the heart and low uptake in adjacent non-target tissues, such as the liver.  Another 18F-labeled compound closely related to the perfusion agent is being investigated for imaging drug resistance in tumors.  The second 18F project focuses on the development of a new imaging agent for the D2 receptor in the brain.  In contrast to existing D2 imaging agents, which are D2 antagonists and thus show only total D2 receptor density, the proposed compound is a D2 agonist, which, if successful, will allow the differentiation of the functional state D2 receptors.  These differences may be important in diseases such as schizophrenia, but there is currently no way to measure this in vivo.

Dr. Packard, in collaboration with Dr. Jason Dearling, also supports the “Imogen” imaging core at BCH.  This resource provides a mechanism for probe development, small-animal imaging, and data analysis for the research community, both within BCH as well as to external investigators.

Research Background

Dr. Alan Packard received his PhD in inorganic chemistry from Colorado State University and completed a postdoctoral fellowship in technetium chemistry at the University of Cincinnati. In addition to his research, Dr. Packard is also active in the leadership of the Society of Nuclear Medicine and Molecular Imaging where he currently serves as President-Elect./p>

 

Publications

  1. CD45-PET is a robust, non-invasive tool for imaging inflammation. Nature. 2025 Jan 22. View Abstract
  2. Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine. Nat Biomed Eng. 2024 Nov; 8(11):1396-1411. View Abstract
  3. Low-Fouling Zwitterionic Polymeric Colloids as Resuscitation Fluids for Hemorrhagic Shock. Adv Mater. 2022 Nov; 34(47):e2207376. View Abstract
  4. The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D2 Agonist [18F]MCL-524. Chemistry (Basel). 2021 Sep; 3(3):1047-1056. View Abstract
  5. Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics. Nat Nanotechnol. 2021 09; 16(9):1030-1038. View Abstract
  6. A Challenging and Rewarding Year. J Nucl Med. 2021 Jun 01; 62(6):32N. View Abstract
  7. SNMMI Leadership Update: A Year of Progress Amid a Pandemic. J Nucl Med. 2021 May 10; 62(5):17N-22N. View Abstract
  8. SNMMI Mid-Winter and ACNM Annual Meeting. J Nucl Med. 2021 Mar; 62(3):11N. View Abstract
  9. Advocating for Our Field. J Nucl Med. 2021 Mar; 62(3):15N. View Abstract
  10. 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
  11. SNMMI Diversity, Equity, and Inclusion Task Force Statement. J Nucl Med. 2021 Jan; 62(1):13N. View Abstract
  12. SNMMI Leadership Update: Improving Radionuclide Availability. J Nucl Med. 2021 Jan; 62(1):22N. View Abstract
  13. SNMMI Leadership Update: Research-The Key to Nuclear Medicine's Past and Future. J Nucl Med. 2020 11; 61(11):23N. View Abstract
  14. In vivo detection of antigen-specific CD8+ T cells by immuno-positron emission tomography. Nat Methods. 2020 10; 17(10):1025-1032. View Abstract
  15. SNMMI Leadership Update: Diversity, Equity, and Inclusion. J Nucl Med. 2020 Sep; 61(9):24N. View Abstract
  16. Mitochondrial transplantation by intra-arterial injection for acute kidney injury. Am J Physiol Renal Physiol. 2020 09 01; 319(3):F403-F413. View Abstract
  17. SNMMI Leadership Update: Notes from the Top. J Nucl Med. 2020 Jul; 61(7):19N. View Abstract
  18. A non-anhydrous, minimally basic protocol for the simplification of nucleophilic 18F-fluorination chemistry. Sci Rep. 2020 04 22; 10(1):6818. View Abstract
  19. A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy. JACC Basic Transl Sci. 2019 Dec; 4(8):871-888. View Abstract
  20. Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2020 01 01; 318(1):L78-L88. View Abstract
  21. 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
  22. Radioactive Transition Metals for Imaging and Therapy. Chem Rev. 2019 01 23; 119(2):870-901. View Abstract
  23. Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation. J Heart Lung Transplant. 2019 01; 38(1):92-99. View Abstract
  24. New chemical and radiochemical routes to [18F]Rho6G-DEG-F, a delocalized lipophilic cation for myocardial perfusion imaging with PET. Medchemcomm. 2017 Oct 01; 8(10):1891-1896. View Abstract
  25. Molecular imaging in nanomedicine - A developmental tool and a clinical necessity. J Control Release. 2017 09 10; 261:23-30. View Abstract
  26. ACR and SNMMI Joint Credentialing Statement for PET/MRI of the Body. J Nucl Med. 2017 07; 58(7):1174-1176. View Abstract
  27. 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
  28. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection. PLoS One. 2016; 11(8):e0160889. View Abstract
  29. Colitis ImmunoPET: Defining Target Cell Populations and Optimizing Pharmacokinetics. Inflamm Bowel Dis. 2016 Mar; 22(3):529-38. View Abstract
  30. In Memoriam: Alan Davison, PhD, 1936-2015. J Nucl Med. 2016 Feb; 57(2):11N-5N. View Abstract
  31. Improved production and processing of 8?Zr using a solution target. Nucl Med Biol. 2016 Jan; 43(1):97-100. View Abstract
  32. Use of [18F]FDG Positron Emission Tomography to Monitor the Development of Cardiac Allograft Rejection. Transplantation. 2015 Sep; 99(9):e132-9. View Abstract
  33. (18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines. Nucl Med Biol. 2015 Oct; 42(10):796-803. View Abstract
  34. 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
  35. American College of Radiology and Society of Nuclear Medicine and Molecular Imaging Joint Credentialing Statement for PET/MR Imaging: Brain. J Nucl Med. 2015 Apr; 56(4):642-5. View Abstract
  36. Convenient synthesis of 18F-radiolabeled R-(-)-N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine. J Labelled Comp Radiopharm. 2014 Dec; 57(14):725-9. View Abstract
  37. Preparation and preliminary evaluation of 63Zn-zinc citrate as a novel PET imaging biomarker for zinc. J Nucl Med. 2014 Aug; 55(8):1348-54. View Abstract
  38. Cyclotron production of (68)Ga via the (68)Zn(p,n)(68)Ga reaction in aqueous solution. Am J Nucl Med Mol Imaging. 2014; 4(4):303-10. View Abstract
  39. Production of 89Zr via the 89Y(p,n)89Zr reaction in aqueous solution: effect of solution composition on in-target chemistry. Nucl Med Biol. 2014 Apr; 41(4):309-16. View Abstract
  40. On the destiny of (copper) species. J Nucl Med. 2014 Jan; 55(1):7-8. View Abstract
  41. 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
  42. Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer. Nucl Med Biol. 2013 Nov; 40(8):1043-8. View Abstract
  43. 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
  44. The future of USP monographs for PET drugs. J Nucl Med. 2013 Mar; 54(3):472-5. View Abstract
  45. Effect of the prosthetic group on the pharmacologic properties of 18F-labeled rhodamine B, a potential myocardial perfusion agent for positron emission tomography (PET). J Med Chem. 2012 Dec 27; 55(24):11004-12. View Abstract
  46. 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
  47. PET-radioimmunodetection of integrins: imaging acute colitis using a 64Cu-labeled anti-ß7 integrin antibody. Methods Mol Biol. 2012; 757:487-96. View Abstract
  48. Radioimmunotherapy: optimizing delivery to solid tumors. Ther Deliv. 2011 May; 2(5):567-72. View Abstract
  49. 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
  50. 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
  51. Biodistribution and stability studies of [18F]fluoroethylrhodamine B, a potential PET myocardial perfusion agent. Nucl Med Biol. 2010 Apr; 37(3):365-70. View Abstract
  52. Some thoughts on the mechanism of cellular trapping of Cu(II)-ATSM. Nucl Med Biol. 2010 Apr; 37(3):237-43. View Abstract
  53. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent. Appl Radiat Isot. 2010 Jan; 68(1):96-100. View Abstract
  54. Synthesis and Characterization of a Tetramethyl Furanone Functionalized Diiminedioxime, A Potential Ligand for Cu Radiopharmaceuticals, and its Copper(II) and Nickel(II) Complexes. Polyhedron. 2009 Mar 12; 28(4):775-781. View Abstract
  55. Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008 Jan; 49(1):68-78. View Abstract
  56. 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
  57. On the strong field dependence and nonlinear response to gadolinium contrast agent of proton transverse relaxation rates in dairy cream. Magn Reson Imaging. 2005 Jul; 23(6):757-64. View Abstract
  58. Fat fractions and spectral T2 values in vertebral bone marrow in HIV- and non-HIV-infected men: a 1H spectroscopic imaging study. Magn Reson Med. 2004 Sep; 52(3):552-8. View Abstract
  59. Assessment of rapid changes in renal blood flow with (191m)Ir, an ultra-short-lived radionuclide. J Nucl Med. 2004 Mar; 45(3):508-11. View Abstract
  60. A lariat-functionalized copper(II) diimine-dioxime complex. Acta Crystallogr C. 2002 Dec; 58(Pt 12):m593-5. View Abstract
  61. Synthesis and biodistribution of a Lipophilic 64Cu-labeled monocationic Copper(II) complex. Nucl Med Biol. 2002 Apr; 29(3):289-94. View Abstract
  62. Histidine residues underlie Congo red binding to A beta analogs. Amyloid. 2000 Sep; 7(3):179-88. View Abstract
  63. Rapid renal single-photon emission tomography by continuous infusion of iridium-191m. Eur J Nucl Med. 1999 May; 26(5):489-93. View Abstract
  64. Synthesis and biodistribution of 64Cu-labeled monocationic diiminedioxime copper(II) complexes. Nucl Med Biol. 1998 Aug; 25(6):531-7. View Abstract
  65. Comparison of uptake of 99mTc-alkylisonitriles in the rat 9L gliosarcoma tumor model. Nucl Med Biol. 1997 Jan; 24(1):21-5. View Abstract
  66. Ictal and interictal technetium-99m-bicisate brain SPECT in children with refractory epilepsy. J Nucl Med. 1996 Jul; 37(7):1101-6. View Abstract
  67. An improved 191Os/191mIr generator using a hybrid anion exchanger. Nucl Med Biol. 1995 Oct; 22(7):887-91. View Abstract
  68. Tumor uptake of 99mTc-MIBI and 201Tl by a 9L gliosarcoma brain tumor model in rats. Nucl Med Biol. 1993 Aug; 20(6):773-6. View Abstract
  69. Thallium-201 versus technetium-99m-MIBI SPECT in evaluation of childhood brain tumors: a within-subject comparison. J Nucl Med. 1993 Jul; 34(7):1045-51. View Abstract
  70. Evaluation of osmium(II)-nitrosyl complexes as a method to increase the yield of the 191Os-191mIr generator. Int J Rad Appl Instrum B. 1992 Apr; 19(3):357-62. View Abstract
  71. SPECT imaging of pediatric brain tumor with hexakis (methoxyisobutylisonitrile) technetium (I). J Nucl Med. 1990 Dec; 31(12):2040-1. View Abstract
  72. Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3. Int J Rad Appl Instrum B. 1989; 16(3):291-4. View Abstract
  73. An osmium-191/iridium-191m radionuclide generator using an oxalato osmate parent complex. J Nucl Med. 1987 Oct; 28(10):1571-6. View Abstract
  74. Evaluation of the renal clearance of technetium-99m PAHIDA in dogs. J Nucl Med. 1987 May; 28(5):907-9. View Abstract
  75. Comparison of ultrashort-lived iridium-191m with technetium-99m for first pass radionuclide angiocardiographic evaluation of right and left ventricular function in adults. J Am Coll Cardiol. 1986 Jun; 7(6):1295-302. View Abstract
  76. The development of an 191Os----191mIr generator using an osmium chelate parent complex--I. Trans-dioxobismalonatoosmate(VI). Int J Rad Appl Instrum B. 1986; 13(5):519-22. View Abstract
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  78. Electrophysiological observations on a sound-producing fish. Nature. 1960 Jul 02; 187:63-4. View Abstract

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