Research

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Alan Packard, PhD

Alan Packard, PhD
Department:
Radiology Research
Division
Hospital Title:
Senior Research Associate Nuclear Medicine and Molecular Imaging
Academic Title:
Assistant Professor of Radiology, Harvard Medical School
Research Focus Area:
Radiopharmaceutical development
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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. 

About Alan Packard 

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.  Dr. Packard is active in the leadership of the Society of Nuclear Medicine and Molecular Imaging where he currently serves as general program chair. 

Publications

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  1. 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.
  2. 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.
  3. Kronauge J, Packard AB. In Memoriam: Alan Davison, PhD, 1936-2015. J Nucl Med. 2016 Feb; 57(2):11N-5N.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Dearling JL, Packard AB. On the destiny of (copper) species. J Nucl Med. 2014 Jan; 55(1):7-8.
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  12. 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.
  13. Rajkumar V, Dearling JL, Packard A, Pedley RB. Radioimmunotherapy: optimizing delivery to solid tumors. Ther Deliv. 2011 May; 2(5):567-72.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. Kiani S, Staples RJ, Packard AB. A lariat-functionalized copper(II) diimine-dioxime complex. Acta Crystallogr C. 2002 Dec; 58(Pt 12):m593-5.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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 1; 20(3):678-87.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
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