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.

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>

Researcher Services

Researcher Areas

  • Radiopharmaceutical Development

Research Departments

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Inkster JAH, Akurathi V, Sromek AW, Chen Y, Neumeyer JL, Packard AB. A non-anhydrous, minimally basic protocol for the simplification of nucleophilic 18F-fluorination chemistry. Sci Rep. 2020 Apr 22; 10(1):6818. View abstract
  2. Shin B, Saeed MY, Esch JJ, Guariento A, Blitzer D, Moskowitzova K, Ramirez-Barbieri G, Orfany A, Thedsanamoorthy JK, Cowan DB, Inkster JA, Snay ER, Staffa SJ, Packard AB, Zurakowski D, Del Nido PJ, McCully JD. 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
  3. Moskowitzova K, Orfany A, Liu K, Ramirez-Barbieri G, Thedsanamoorthy JK, Yao R, Guariento A, Doulamis IP, Blitzer D, Shin B, Snay ER, Inkster JAH, Iken K, Packard AB, Cowan DB, Visner GA, Del Nido PJ, McCully JD. 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
  4. Butch ER, Mead PE, Amador Diaz V, Tillman H, Stewart E, Mishra JK, Kim J, Bahrami A, Dearling JLJ, Packard AB, Stoddard SV, Vavere AL, Han Y, Shulkin BL, Snyder SE. 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. Boros E, Packard AB. Radioactive Transition Metals for Imaging and Therapy. Chem Rev. 2019 01 23; 119(2):870-901. View abstract
  6. Moskowitzova K, Shin B, Liu K, Ramirez-Barbieri G, Guariento A, Blitzer D, Thedsanamoorthy JK, Yao R, Snay ER, Inkster JAH, Orfany A, Zurakowski D, Cowan DB, Packard AB, Visner GA, Del Nido PJ, McCully JD. Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation. J Heart Lung Transplant. 2019 01; 38(1):92-99. View abstract
  7. Inkster JAH, Zhang S, Akurathi V, Belanger A, Dubey S, Treves T, Packard AB. 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
  8. Dearling JLJ, Packard AB. Molecular imaging in nanomedicine - A developmental tool and a clinical necessity. J Control Release. 2017 09 10; 261:23-30. View abstract
  9. Subramaniam RM, Jadvar H, Colletti PM, Guimaraes A, Gullapali R, Iagaru AH, McConathy J, Meltzer CC, Nadel H, Noto RB, Packard AB, Rohren EM, Oates ME. ACR and SNMMI Joint Credentialing Statement for PET/MRI of the Body. J Nucl Med. 2017 07; 58(7):1174-1176. View abstract
  10. Dearling JLJ, Packard AB. 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
  11. Cowan DB, Yao R, Akurathi V, Snay ER, Thedsanamoorthy JK, Zurakowski D, Ericsson M, Friehs I, Wu Y, Levitsky S, Del Nido PJ, Packard AB, McCully JD. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection. PLoS One. 2016; 11(8):e0160889. View abstract
  12. Dearling JL, Daka A, Veiga N, Peer D, Packard AB. Colitis ImmunoPET: Defining Target Cell Populations and Optimizing Pharmacokinetics. Inflamm Bowel Dis. 2016 Mar; 22(3):529-38. View abstract
  13. Kronauge J, Packard AB. In Memoriam: Alan Davison, PhD, 1936-2015. J Nucl Med. 2016 Feb; 57(2):11N-5N. View abstract
  14. Pandey MK, Bansal A, Engelbrecht HP, Byrne JF, Packard AB, DeGrado TR. Improved production and processing of 8?Zr using a solution target. Nucl Med Biol. 2016 Jan; 43(1):97-100. View abstract
  15. Daly KP, Dearling JL, Seto T, Dunning P, Fahey F, Packard AB, Briscoe DM. Use of [18F]FDG Positron Emission Tomography to Monitor the Development of Cardiac Allograft Rejection. Transplantation. 2015 Sep; 99(9):e132-9. View abstract
  16. Bartholomä MD, Zhang S, Akurathi V, Pacak CA, Dunning P, Fahey FH, Cowan DB, Treves ST, Packard AB. (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
  17. Dearling JL, Paterson BM, Akurathi V, Betanzos-Lara S, Treves ST, Voss SD, White JM, Huston JS, Smith SV, Donnelly PS, Packard AB. 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
  18. Jadvar H, Subramaniam RM, Berman CG, Boada F, Colletti PM, Guimaraes AR, McConathy J, Meltzer CC, Noto RB, Packard AB, Rohren EM, Oates ME. 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
  19. Sromek AW, Zhang S, Akurathi V, Packard AB, Li W, Alagille D, Morley TJ, Baldwin R, Tamagnan G, Neumeyer JL. 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
  20. DeGrado TR, Pandey MK, Byrne JF, Engelbrecht HP, Jiang H, Packard AB, Thomas KA, Jacobson MS, Curran GL, Lowe VJ. 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
  21. Pandey MK, Byrne JF, Jiang H, Packard AB, DeGrado TR. 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
  22. Pandey MK, Engelbrecht HP, Byrne JP, Packard AB, DeGrado TR. 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
  23. Dearling JL, Packard AB. On the destiny of (copper) species. J Nucl Med. 2014 Jan; 55(1):7-8. View abstract
  24. O'Neill AF, Dearling JL, Wang Y, Tupper T, Sun Y, Aster JC, Calicchio ML, Perez-Atayde AR, Packard AB, Kung AL. 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
  25. Bartholomä MD, He H, Pacak CA, Dunning P, Fahey FH, McGowan FX, Cowan DB, Treves ST, Packard AB. 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
  26. Dearling JL, Barnes JW, Panigrahy D, Zimmerman RE, Fahey F, Treves ST, Morrison MS, Kieran MW, Packard AB. 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
  27. Schwarz S, Norenberg J, Berridge M, Dragotakes S, Hung J, Link J, Mason NS, Mattmuller S, Nickel RA, Packard A, Paolino J, Petry N, Ponto J, Quinton TM, Seifert KL, Swanson D, Weiner RE, Zigler S. The future of USP monographs for PET drugs. J Nucl Med. 2013 Mar; 54(3):472-5. View abstract
  28. Bartholomä MD, Gottumukkala V, Zhang S, Baker A, Dunning P, Fahey FH, Treves ST, Packard AB. 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
  29. Vavere AL, Butch ER, Dearling JL, Packard AB, Navid F, Shulkin BL, Barfield RC, Snyder SE. 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
  30. Dearling JL, Packard AB. PET-radioimmunodetection of integrins: imaging acute colitis using a 64Cu-labeled anti-ß7 integrin antibody. Methods Mol Biol. 2012; 757:487-96. View abstract
  31. Rajkumar V, Dearling JL, Packard A, Pedley RB. Radioimmunotherapy: optimizing delivery to solid tumors. Ther Deliv. 2011 May; 2(5):567-72. View abstract
  32. Dearling JL, Voss SD, Dunning P, Snay E, Fahey F, Smith SV, Huston JS, Meares CF, Treves ST, Packard AB. 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
  33. Dearling JL, Park EJ, Dunning P, Baker A, Fahey F, Treves ST, Soriano SG, Shimaoka M, Packard AB, Peer D. 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
  34. Gottumukkala V, Heinrich TK, Baker A, Dunning P, Fahey FH, Treves ST, Packard AB. 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
  35. Dearling JL, Packard AB. Some thoughts on the mechanism of cellular trapping of Cu(II)-ATSM. Nucl Med Biol. 2010 Apr; 37(3):237-43. View abstract
  36. Heinrich TK, Gottumukkala V, Snay E, Dunning P, Fahey FH, Ted Treves S, Packard AB. 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
  37. Kiani S, Staples RJ, Treves ST, Packard AB. 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
  38. Grant FD, Fahey FH, Packard AB, Davis RT, Alavi A, Treves ST. Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med. 2008 Jan; 49(1):68-78. View abstract
  39. Voss SD, Smith SV, DiBartolo N, McIntosh LJ, Cyr EM, Bonab AA, Dearling JL, Carter EA, Fischman AJ, Treves ST, Gillies SD, Sargeson AM, Huston JS, Packard AB. 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
  40. Mulkern RV, Hung YP, Ababneh Z, Maier SE, Packard AB, Uluer MC, Kacher DF, Gambarota G, Voss S. 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
  41. Mulkern RV, Huang J, Vajapeyam S, Packard AB, Oshio K, Grinspoon S. 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
  42. Treves ST, Packard AB, Fung LC. 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
  43. Kiani S, Staples RJ, Packard AB. A lariat-functionalized copper(II) diimine-dioxime complex. Acta Crystallogr C. 2002 Dec; 58(Pt 12):m593-5. View abstract
  44. Packard AB, Kronauge JF, Barbarics E, Kiani S, Treves ST. Synthesis and biodistribution of a Lipophilic 64Cu-labeled monocationic Copper(II) complex. Nucl Med Biol. 2002 Apr; 29(3):289-94. View abstract
  45. Inouye H, Nguyen JT, Fraser PE, Shinchuk LM, Packard AB, Kirschner DA. Histidine residues underlie Congo red binding to A beta analogs. Amyloid. 2000 Sep; 7(3):179-88. View abstract
  46. Treves ST, Fung L, Packard AB. Rapid renal single-photon emission tomography by continuous infusion of iridium-191m. Eur J Nucl Med. 1999 May; 26(5):489-93. View abstract
  47. Packard AB, Kronauge JF, Day PJ, Treves ST. Synthesis and biodistribution of 64Cu-labeled monocationic diiminedioxime copper(II) complexes. Nucl Med Biol. 1998 Aug; 25(6):531-7. View abstract
  48. Packard AB, Barbarics E, Kronauge JF, Wen PY, Day PJ, Jones AG. Comparison of uptake of 99mTc-alkylisonitriles in the rat 9L gliosarcoma tumor model. Nucl Med Biol. 1997 Jan; 24(1):21-5. View abstract
  49. Packard AB, Roach PJ, Davis RT, Carmant L, Davis R, Riviello J, Holmes G, Barnes PD, O'Tuama LA, Bjornson B, Treves ST. Ictal and interictal technetium-99m-bicisate brain SPECT in children with refractory epilepsy. J Nucl Med. 1996 Jul; 37(7):1101-6. View abstract
  50. Packard AB, Day PJ, Treves ST. An improved 191Os/191mIr generator using a hybrid anion exchanger. Nucl Med Biol. 1995 Oct; 22(7):887-91. View abstract
  51. Packard AB, Kronauge JF, Limpa-Amara N, Lampson L, O'Tuama LA, Jones AG. 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
  52. O'Tuama LA, Treves ST, Larar JN, Packard AB, Kwan AJ, Barnes PD, Scott RM, Black PM, Madsen JR, Goumnerova LC, et al. 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
  53. Packard AB, Lambert C. 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
  54. O'Tuama LA, Packard AB, Treves ST. SPECT imaging of pediatric brain tumor with hexakis (methoxyisobutylisonitrile) technetium (I). J Nucl Med. 1990 Dec; 31(12):2040-1. View abstract
  55. Packard AB, Srivastava SC, Richards P, Meinken GE, Ford L, Benson WR. 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
  56. Packard AB, Treves ST, O'Brien GM, Lim KS. An osmium-191/iridium-191m radionuclide generator using an oxalato osmate parent complex. J Nucl Med. 1987 Oct; 28(10):1571-6. View abstract
  57. Summerville DA, Packard AB, Bartynski B, Lim KS, Chervu LR, Treves ST. Evaluation of the renal clearance of technetium-99m PAHIDA in dogs. J Nucl Med. 1987 May; 28(5):907-9. View abstract
  58. Heller GV, Treves ST, Parker JA, Duke LA, O'Brien GM, Davis RT, Fitzgibbon C, Packard AB. 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
  59. Packard AB, O'Brien GM, Treves S. 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