Radiopharmaceutical research center

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Radiopharmaceutical research center

Hank F. Kung

Hank F. Kung
Hank F. Kung, Ph.D.,
Professor of Neurobiology, Beijing Institute For Brain Disorder, Capital Medical University in Beijing, China (since 2014)
Professor Emeritus of Radiology and Pharmacology at the University of Pennsylvania, USA (since 2014)
Dr. Kung did his undergraduate work in chemistry at the Cheng Kung University, Taiwan. In 1976, he received his PhD in medicinal chemistry from the University of Buffalo, School of Pharmacy and Pharmaceutical Sciences. After postdoctoral training under Dr. Monte Blau at Roswell Park Memorial Institute, Dr. Kung joined the Department of Nuclear Medicine at the University of Buffalo, first as an Assistant Professor, and later as Associate Professor of Nuclear Medicine. In 1987 Dr. Kung moved his research group to the Department of Radiology, University of Pennsylvania. He became Professor of Radiology and Pharmacology at the University of Pennsylvania (UPenn) in 1993.
Dr. Kung’ s research activities cover a wide spectrum of scientific disciplines including drug design, organic synthesis, radiochemistry, receptor pharmacology, pharmacokinetics, and Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging. Over the past three decades, the dozens of research projects were granted from NIH for the development of imaging agents. Recent years, Dr. Kung is also working as an Investigator on the Pancreatic Cancer Dream Team with the Stand up to Cancer (SU2C) initiative, and continue to conduct research projects in the study of glutamine metabolism in cancer patients and aromatase inhibitors for tumor imaging.
One of Dr. Kung’s most well-known achievements is the development of the FDA first approved β-amyloid plaques imaging agent Florbetapir 18F (AmyvidTM, Avid/Eli Lilly), which allow for the in-vivo diagnosis of Alzheimer's disease.
There are many commercially available PET and SPECT imaging agents, originally prepared in his laboratory, have been developed, and applied in human studies, including123I-HIPDM (Brain perfusion imaging); 123I-TISCH (D1 receptor); 123I-IBZM , 123I-IBF and 123I-FIDA2 (D2 and D3 receptors); 123I-IPT (dopamine transporter), 123I-ADAM( serotonin transporter) and 123I-p-MPPI(5HT1a receptor) .  Specifically, 123I-IBZM (D2 and D3 receptors imaging) and 99mTc-TRODAT-1 (Dopamine Transporter imaging, the milestone achievement for SPECT) are used worldwide for differential diagnosis of Parkinson's disease for SPECT. Recently, several PET imaging agents, including AmyvidTM (Florbetapir, AV-45, Eli Lilly), NeuraCeqTM (Florbetaben, AV-1) and Florbenazine F-18 (AV-133), developed in the Kung lab for diagnosis of Alzheimer’s and Parkinson’s disease have moved from bench to clinics. Several C-11 and F-18 glutamine-based PET imaging agents targeting tumor metabolism have been prepared and tested. They may be useful to image changes in tumor metabolism via glutaminolysis therefore showing negative scans with FDG/PET.
Dr. Kung serves on several editorial boards including the Journal of Medicinal Chemistry. With more than thirty-five years experience in the field of radiopharmaceutical chemistry, He has published over 310 peer-reviewed scientific papers and has received more than 40 US patents.

He received many awards, including famous awards:

1988    Jacob Javits Award for Neuroscience, NIH
1997    Springer Award for the Best Paper in Basic Science, European Society of Nuclear Medicine
2004    Paul C. Aebersold Award for outstanding achievement in basic science applied to nuclear medicine, Society of Nuclear Medicine
2012    Distinguished Investigator, Academy of Radiology Research
2013    Kuhl-Lassen Award for Research in Brain Imaging, Society of Nuclear Medicine(SNMMI) (honors a scientist who has made significant contributions to the field of functional brain imaging using SPECT and PET)
2014    David and Jane Chu Lectureship, University of Buffalo

Five of the most significant contributions to science are:
1. Dr. Kung is the original inventor of [18F]AV1 (florbetaben, Neurqceq, developed by Piramal Biotechnolgy) and [18F]AV-45 (florbetapir, Amyvid, developed by Avid/Eli Lilly) for detecting Aβ plaques in the brain by PET. These two imaging agents were originally prepared in Kung’s laboratory; they have been approved by the FDA in 2012 and 2014, respectively, for assisting the diagnosis of Alzheimer’s disease (AD). It is expected that in the future these agents will be widely used to help neurologists in the diagnosis and monitoring for treatment of AD patients.        
a. Zhu L, Ploessl K, Kung HF. Chemistry. Expanding the scope of fluorine tags for PET imaging. Science. 2013 Oct 25;342(6157):429-30. PubMed PMID: 24159034.
Kung HF. The β-Amyloid Hypothesis in Alzheimer's Disease: Seeing Is Believing. ACS Med Chem Lett. 2012 Apr 12;3(4):265-7. PubMed PMID: 24936237; PubMed Central PMCID: PMC4056942.
b. Choi SR, Schneider JA, Bennett DA, Beach TG, Bedell BJ, Zehntner SP, Krautkramer MJ, Kung HF, Skovronsky DM, Hefti F, Clark CM. Correlation of amyloid PET ligand florbetapir F 18 binding with Aβ aggregation and neuritic plaque deposition in postmortem brain tissue. Alzheimer Dis Assoc Disord. 2012 Jan-Mar;26(1):8-16. PubMed PMID: 22354138; PubMed Central PMCID: PMC3286131.
c. Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML, Krautkramer MJ, Kung HF, Coleman RE, Doraiswamy PM, Fleisher AS, Sabbagh MN, Sadowsky CH, Reiman EP, Zehntner SP, Skovronsky DM. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011 Jan 19;305(3):275-83. PubMed PMID: 21245183.
d. Zhang W, Kung MP, Oya S, Hou C, Kung HF, 18F-labeled styrylpyridines as PET agents for amyloid plaque imaging. Nucl Med Biol. 2007 Jan; 34(1) : 89-97

2. Dr. Kung’s laboratory has developed [18F]FP-DTBZ (AV133, fluorbenazine) for imaging vesicular monoamine transporters (VMAT2) in the brain by PET was first prepared and tested in his laboratory in collaboration with Dr. Michael Kilbourn, University of Michigan. The new imaging agent is useful for diagnosis of Parkinson’s disease (PD). Avid/Eli Lilly is currently supporting the phase II/phase III studies in PD patients.
a. Zhu L, Ploessl K, Kung HF. PET/SPECT imaging agents for neurodegenerative diseases. Chem Soc Rev. 2014 Oct 7;43(19):6683-91. PubMed PMID: 24676152; PubMed Central PMCID: PMC4159420.
b. Okamura N, Villemagne VL, Drago J, Pejoska S, Dhamija RK, Mulligan RS, Ellis JR, Ackermann U, O'Keefe G, Jones G, Kung HF, Pontecorvo MJ, Skovronsky D, Rowe CC. In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133. J Nucl Med. 2010 Feb;51(2):223-8. PubMed PMID: 20080893.
c. Zhu L, Liu Y, Plössl K, Lieberman B, Liu J, Kung HF. An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular monoamine transporter 2. Nucl Med Biol. 2010 Feb;37(2):133-41. PubMed PMID: 20152712.
d. Goswami R, Ponde DE, Kung MP, Hou C, Kilbourn MR, Kung HF. Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol. 2006 Aug ;33(6):685-94

3. Dr. Kung’s laboratory has also developed Tc-99m TRODAT-1, first in its class, as a Tc-99m-based SPECT imaging agent targeting dopamine transporters useful for the diagnosis of Parkinson’s disease. Tc-99m TRODAT-1 is commercial available in Taiwan (China), Iran and other countries.
a. Kushner SA, McElgin WT, Kung MP, Mozley PD, Plössl K, Meegalla SK, Mu M, Dresel S, Vessotskie JM, Lexow N, Kung HF. Kinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent. J Nucl Med. 1999 Jan;40(1):150-8. PubMed PMID: 9935071.
b. Mozley PD, Stubbs JB, Plössl K, Dresel SH, Barraclough ED, Alavi A, Araujo LI, Kung HF. Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters. J Nucl Med. 1998 Dec;39(12):2069-76. PubMed PMID: 9867143.
c. Meegalla SK, Plössl K, Kung MP, Stevenson DA, Mu M, Kushner S, Liable-Sands LM, Rheingold AL, Kung HF. Specificity of diastereomers of [99mTc]TRODAT-1 as dopamine transporter imaging agents. J Med Chem. 1998 Feb 12;41(4):428-36. PubMed PMID: 9484494.
d. Kung HF, Kim HJ, Kung MP, Meegalla SK, Plössl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med. 1996 Nov;23(11):1527-30. PubMed PMID: 8854853.

4. New glutamines, 4-[18F]fluoro-glutamine and [11C]glutamine, used for imaging changes of metabolism in tumor cells, were first prepared and tested in his laboratory. They may be useful in cancer patients who showed a different genetic disposition in using an alternative energy source, glutamine, for sustaining tumor growth. These new tumor imaging agents may be useful to assess FDG negative tumors that have switched the energy metabolism by using glutamine. This project was originally in collaboration with Dr. Craig Thompson, who has moved from UPenn to Sloan Kettering Memorial Cancer Center.
a. Venneti S, Dunphy MP, Zhang H, Pitter KL, Zanzonico P, Campos C, Carlin SD, La Rocca G, Lyashchenko S, Ploessl K, Rohle D, Omuro AM, Cross JR, Brennan CW, Weber WA, Holland EC, Mellinghoff IK, Kung HF, Lewis JS, Thompson CB. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med. 2015 Feb 11;7(274):274ra17. PubMed PMID: 25673762; PubMed Central PMCID: PMC4431550.
b. Lieberman BP, Ploessl K, Wang L, Qu W, Zha Z, Wise DR, Chodosh LA, Belka G, Thompson CB, Kung HF. PET imaging of glutaminolysis in tumors by 18F-(2S,4R)4-fluoroglutamine. J Nucl Med. 2011 Dec;52(12):1947-55. PubMed PMID: 22095958.
c. Qu W, Zha Z, Ploessl K, Lieberman BP, Zhu L, Wise DR, Thompson CB, Kung HF. Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. J Am Chem Soc. 2011 Feb 2;133(4):1122-33. PubMed PMID: 21190335.

5. Kung’s laboratory was the first group to develop [123I]IBZM for SPECT imaging of D2/D3 dopamine receptors in Parkinson’s patients. This agent is commercially available in Europe and has been used widely in patient studies.
a.  Kung HF, Pan S, Kung MP, Billings JJ, Kasliwal R, Reilley J, Alavi A. In Vitro and in Vivo Evaluation of [123I]IBZM: A Potential CNS D2 Dopamine Receptor Imaging Agent. J Nucl Med, 30:88-92, 1989. PMID: 2783457
 b. Kung HF, Kasliwal R, Pan S, Kung MP, Mach RH, Guo YZ. Dopamine D2 Receptor Imaging Radiopharmaceuticals: Synthesis, Radiolabeling and in Vitro Binding of R-(+) and S-(-)3-Iodo-2-Hydroxy-6-Methoxy-N- [(1-Ethyl)-2 Pyrrolidinyl)Methyl] Benzamide (IBZM). J Med Chem, 31:1039-1043, 1988. PMID: 2966245
 c. Kung HF, Alavi A, Chang W, Kung MP, Keyes JW Jr., Velchik M, Billings JJ, Pan S, Noto R, Rausch A, Reilley J. In Vivo SPECT Imaging of D2 Dopamine Receptors: Initial Studies with [123I]IBZM in Humans. J Nucl Med, 31:573-579, 1990. PMID:2140408
 d. Seibyl JP, Woods SW, Zoghbi SS, Baldwin RM, Dey HM, Goddard AW, Zea-Ponce Y, Zubal G, Germine M, Smith EO, Heninger GR, Charney DS, Kung HF, Alavi A, Hoffer PB, Innis RB. Dynamic SPECT Imaging of Dopamine D2 Receptors in Human Subjects with [123I]IBZM. J Nucl Med, 33:1964-1971, 1992. PMID: 1432157