AVA)LIDNYee
`OYee A)
`October 2001
`
`‘October 17, 2001
`HEALTH SCIENCES ~
`LIBRARIES
`
`IPR PETITION
`
`Co 4
`g
`7?
`’ The Official Publication
`of the Society of Nuclear Medicine, UNAM
`
`Se WAMeet
`\ Nuclear Medicine
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`ATA Exhibit 1031
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`MAIA V. BRACCO
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`MAIA Exhibit 1031
`MAIA V. BRACCO
`IPR PETITION
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`

`The Journal of Nuclear Medicine
`
`Official Publication of the Society ofNuclear Medicine
`
`COPYRIGHT®©2001 by the Society ofNuclear Medicine,
`Inc. All rights reserved. No part ofthis work maybe repro-
`duced or translated without permission from the copy-
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`each author of accepted manuscripts must sign a state-
`ment transferring copyright. See Information for Authors
`for further explanation. Available on the Web for down-
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`WILLIAM J. BERTERA
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`THEJOURNAL OF NUCLEAR MEDICINE(ISSN 0161-
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`R. Eowarp CoLeman, MD
`Chairman
`Ettas H. Botvinick, MD
`SIMINDOKHT DapPARVAR, MD
`Susan A. GILBERT, CNMT
`STANLEY J. GoLDsMITH, MD
`MICHAEL M. GraHaM, MD, PHD
`Mark W. Grocu, PHD
`MILTON J. GuipeRTEAU, MD
`HEINRICH SCHELBERT, MD, PHD
`ARNOLD M. STRASHUN, MD
`H. WILLIAM Strauss, MD
`Katuy S. THomas, CNMT
`RonapS. Trkorsky, PHD
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`

`|
`
`| |
`
`1457
`
`*mT¢-Sestamibi Retention Characteristics
`
`Volume 42, Number 10 ¢ October 2001
`During Pharmacologic Hyperemiain Human
`Seeneeeeeee
`Myocardium: Comparison with Coronary F|
`ow
`Reserve Measured by DopplerFlowire
`Junichi Taki, Susumu Fujino, Kenichi Nakajima,
`Ichiro Matsunari, Hideaki Okazaki, Takashi Saga,
`Hisashi Bunko, and Nerihisa Tonami
`
`
`
`Official Publication of
`the Society of Nuclear Medicine
`
`1464
`
`Clinical Impact of ‘F-FDG PETin Thyroid
`Carcinoma Patients with Elevated Thyroglobuiin |
`Levels and Negative '9'l Scanning Results
`/
`After Therapy
`Badia O. Helal, Pascal Merlet,
`Marie-Elisabeth Toubert, Brigitte Franc,
`Claire Schvartz, Haléne Gauthier-Koelesnikoy,
`Alain Prigent, and André Syrota
`
`§
`
`|
`
`|
`
`\
`
`|
`j\
`
`| \
`
`|
`
`{
`|
`
`\
`
`i
`f
`
`||
`
`14N
`
`Public Affairs Update
`William Uffelman
`
`16N
`
`Unexpected Shortfalls of Two Nuclear Medicine
`Pharmaceuticals
`
`25N
`
`25N
`
`26N
`
`28N
`
`SNM Executive Director Search
`
`Keep in Mind
`
`Loevinger-Berman Award Presented to Keith F.
`Eckerman
`
`In Memoriam: Richard Lambrecht, PhD,
`1943-2001
`MathewL. Thakur, PhD
`
`3ON
`
`SNM Announces Education Initiatives
`
`32N
`
`34N
`
`Basic Science CD-ROM:Filling a Need, Fulfilling
`a Mission
`
`SNM Issues Two New Volumesin Nuclear
`Cardiology Self-Study Series
`
`37N
`
`Newsbriefs
`
`38N
`
`Erratum
`
`1470
`
`Serum Thyroglobulin Concentrations and
`131] Whole-Body Scan Resultsin Patients
`with Differentiated Thyroid Carcinoma After
`Administration of Recombinant Human Thyroid-
`Stimulating Hormone
`Alessia David, Annabella Blotta, Marta Bondanelli,
`Roberta Rossi, Elio Roti, Lewis E. Braverman,
`Luciano Busutti, and Ettore C. degli Uberti
`
`1476
`
`Expression of Multidrug Resistance Protein
`and Messenger RNACorrelate with "Tc-MIBI
`Imaging in Patients with Lung Cancer
`Jinshan Zhou, Kotaro Higashi, Yoshimichi Ueda,
`Yuko Kodama, Dachuan Guo, Fumiko Jisaki,
`Aya Sakurai, Tsutomu Takegami, Shogo Katsuda,
`and Itaru Yamamoto
`
`1484
`
`Determination of GlomerularFiltration Rate
`by Means of Newly DevelopedPlastic
`Scintillation Counter Both With and
`Without Dilution Procedures
`
`CLINICAL INVESTIGATIONS
`
`Kazuo Itoh
`
`1441
`
`Donepezil Hydrochloride Preserves Regional
`Cerebral Blood Flow in Patients with
`Alzheimer’s Disease
`Seigo Nakano, Takashi Asada, Hiroshi Matsuda,
`Masatake Uno, and Masaru Takasaki
`
`1446
`
`1451
`
`Fractal Analysis of Cerebral Blood Flow
`Distribution in Alzheimer’s Disease
`Michinobu Nagao, Kenya Murase, Takanori Kikuchi,
`Manabu Ikeda, Akihiko Nebu, Ryuji Fukuhara,
`Yoshifumi Sugawara, Hitoshi Miki, and Junpei Ikezoe
`Clinical Impact of Combination of Scatter,
`Attenuation Correction, and Depth-Dependent
`Resolution Recovery for 2°'T] Studies
`Francois Harel, Rémi Génin, Doumit Daou,
`Rachida Lebtahi, Nicolas Delahaye, Badia O. Helal,
`Dominique Le Guludec, and Mare FaraggiDe
`
`1489
`
`Comparison of['8F]FDG PET and ”"TI SPECTin
`Evaluation of Pulmonary Nodules
`Kotaro Higashi, Yoshimichi Ueda, Tsutomu Sakiwma,
`Hiroyasu Seki, Manabu Oguchi, Mitsuru Taniguchi,
`Suzuka Taki, Hisao Tonami, Shogo Katsuda,
`and Itaru Yamamoto
`
`1497
`
`Invited Commentary: Changing Pattern of
`Lung Cancerand Its Imaging: *°'Tl SPECT
`Versus ['8F]FDG PET
`Kazuo Kubota
`
`1499
`
`CONTINUING EDUCATION
`ing |
`Technical Aspects of Myocardial SPECTImad!
`aa
`Guido Germano
`
`
`
`
`

`

`1551
`
`FDG Uptake and Glucose Transporter Subtype
`Expressions in Experimental Tumor and
`Inflammation Models
`
`1556
`
`1563
`
`1571
`
`1579
`
`Takafumi Mochizuki, Eriko Tsukamoto, Yuji Kuge,
`Kakuko Kanegae, Sonji Zhao, Kenji Hikosaka,
`Masuo Hosokawa, Masashi Kohanawa,
`and Nagara Tamaki
`
`Quantification of Serotonin Transporters
`in Nonhuman Primates Using ['?3I]ADAM
`and SPECT
`
`Paul D. Acton, Seok-Rye Choi, Catherine Hou,
`Karl Plossl, and Hank F. Kung
`
`Registration of Emission and Transmission
`Whole-BodyScintillation-Camera Images
`Katarina Sjégreen, Michael Ljungberg, Karin Wingardh,
`Kjell Erlandsson, and Sven-Erik Strand
`
`Accuracy of Ventricular Volume and Ejection
`Fraction Measured by Gated Myocardial SPECT:
`Comparison of 4 Software Programs
`Kenichi Nakajima, Takahiro Higuchi, Junichi Taki,
`Masaya Kawano, and Norihisa Tonami
`
`Phantom Studies for Estimation of Defect Size
`on Cardiac ‘8F SPECT and PET:Implications
`for Myocardial Viability Assessment
`Ichiro Matsunari, Tatsuya Yoneyama,
`Sugako Kanayama, Masamichi Matsudaira,
`Kenichi Nakajima, Junichi Taki, Stephan G. Nekolla,
`Norihisa Tonami, and Kinichi Hisada
`
`Vaey
`
`1586
`
`Book Review
`
`1587
`
`Letters to the Editor
`
`1590
`
`Calendar
`
`40A
`
`44A
`
`Classified Advertising
`
`JNM Direct Response
`
`jnm.snmjournals.org
`Continuing Education Activity
`www.snm.org/education/ce_online.html
`
`Newsline Online
`www.snm.org/about/news_order.html
`
`BASIC SCIENCE INVESTIGATIONS
`| 4508 High-Level Production of a-Particle-Emitting
`|
`21t and Preparation of 2"'At-Labeled
`Antibodies for Clinical Use
`Michael R. Zalutsky, Xiao-Guang Zhao, Kevin L. Alston,
`and Darell Bigner
`"4516 Invited Commentary: Overcoming the Obstacles
`to Clinical Evaluation of 7"'At-Labeled
`Radiopharmaceuticals
`D. Scott Wilbur
`
`| |
`
`|
`1
`
` 1528 Invited Commentary: Multivalent Single-Chain
`
`+ 4519 2™Tc-Labeled Divalent and Tetravalent CC49
`Single-Chain Fv’s: Novel Imaging Agents for
`Rapid In Vivo Localization of Human Colon
`Carcinoma
`Apollina Goel, Janina Baranowska-Kortylewicz,
`Steven H. Hinrichs, James Wisecarver,
`Gabriela Pavlinkova, Sam Augustine, David Colcher,
`Barbara J.M. Booth, and Surinder K. Batra
`
`{
`
`Antibodies for Radioimaging of Tumors
`Syed V.S. Kashmiri
`
`! 1530 Conjugation with 1In-DTPA-Poly(Ethylene
`Glycol) Improves Imaging of Anti-EGF Receptor
`Antibody C225
`Xiaoxia Wen, Qing-Ping Wu, Shi Ke, Lee Ellis,
`Chusilp Charnsangavej, Abraham §. Delpassand,
`Sidney Wallace, and Chun Li
`
`|
`
`1538 Comparative Cellular Catabolism and Retention
`of Astatine-, Bismuth-, and Lead-Radiolabeled
`Internalizing Monoclonal Antibody
`Zhengsheng Yao, Kayhan Garmestani, Karen J. Wong,
`Luke §. Park, Ekaterina Dadachova,
`Alexander Yordanov, Thomas A. Waldmann,
`William C. Eckelman, Chang H. Paik,
`and Jorge A. Carrasquillo
`
`1845 High-Dose TreatmentwithRe-HEDP or
`'8Sm-EDTMP Combined with Amifostine in
`a Rabbit Model
`Winfried Brenner, Willm Uwe Kampen,
`Corinna von Forstner, Corinna Briimmer,
`Maaz Zuhayra, Claus Muhle, Norbert Czech,
`and Eberhard Henze
`
`| j |
`
`\
`
`:
`
`{
`{
`
`
`
`
`

`

`NEWSLINE
`
`Unexpected Shortfalls of Two
`Nuclear Medicine Pharmaceuticals
`
`hrough an unfortunate confluence ofman-
`ufacturing, scheduling, and regulatory
`occurrences, two pharmaceuticals widely
`used in nuclear medicine practice became
`temporarily unavailable for distribution in August.
`Duringthefirst week ofthat month, Bracco Diag-
`nostics Inc. (Princeton, NJ) mailed separate
`letters to customers, notifying them that short-
`ages of Kinevac (sincalide for injection) and
`Choletec (kit for preparation of°™Tc-mebrofenin)
`were imminent.
`
`
`
`In one letter, Marion Meeks, PhD,Director,
`Medical Affairs and Professional Services at
`Bracco, told customers that Kinevac would be
`out of stock and unavailable for approximately
`1 year. “This back-ordersituation is the result
`of issues encountered during a change in manu-
`facturers,” wrote Meeks. “Bracco is committed
`to resolving this situation as soonas possible.”
`Theletter also notedthata rationing program
`would beusedto distribute the remaining inven-
`tory ofKinevac during the monthofAugust. Cus-
`tomers whopurchased Kinevac directly from
`Bracco wereallowed to place one orderfor a max-
`imumoftwo boxes of Kinevac. Radiopharma-
`cies with average monthly orders larger than two
`boxes per monthofKinevacover the past 12
`months were allowed to order their average
`monthly purchase volume.Fulfillment of these
`orders was to be based on product availability,
`with all orders to be placed before September1.
`In the secondletter, dated August 7, Adrian
`Trevisan, Product Manager, Nuclear Medicine
`at Bracco, informed customers of “further
`delays in the transfer of manufacturing” for the
`Choletec kits, Trevisan wrote, “We will continue
`
`our rationing program until product on hand
`is exhausted. At that point, the product will
`go on backorder.” According to the letter,
`the backorder occurred because of “an unex-
`pected business interruption”at oneofthe raw
`material providers.
`
`The Nuclear Medicine
`Community Reacts
`Reaction among nuclear medicine practition-
`ers was oneofdismay, as e-mails and phonecalls
`aboutrationing, shortfalls, and possible alterna-
`tive pharmaceuticals circulated among
`practitioners and Society of Nuclear Medicine
`(SNM) officers andstaff. On August 10, Edward
`B. Silberstein, MD, Chair of the SNM
`Committee on Radiopharmaceuticals, talked
`with Bracco representatives and issued a
`statement on behalfofthe committee. “The good
`newsis that this radiopharmaceutical shortfall
`wasnot a direct business decisionto cut pro-
`duction of materials with a low profit margin,”
`said Silberstein.
`
`The bad news, of course, was that shortages
`would cause inconveniencesto practitioners and
`could affect the quality of patient care in some
`facilities. The experience ofTerence Beven, MD,
`Director of Nuclear Medicine at Our Lady
`of the Lake Regional Medical Center, Baton
`Rouge, LA, is typical of many nuclear medi-
`cine specialists who received the letters from
`Bracco. “At the time we received this news we
`had about a |-month supply ofKinevac,”he noted
`in mid September. “Since that time we have
`obtained about a |-year supply from a numberof
`different sources. Not being able to meetthe
`demandforthese procedures would have an
`adverse impact on our credibility as nuclear
`medicine physicians and causea lossofinterest
`in the specialty in the eyes ofreferring physicians,
`particularly those specialists who havelearned to
`dependon these proceduresas a significant part
`of their patient management.”
`
`Different Reasons for Shortfalls
`With the two announcements coming within
`aspan of8 days, the immediate assumption in the
`nuclear medicine community wasthat the
`shortfalls were related. In fact, although both
`pharmaceuticals were in the middle of a trans-
`(Continued on page 19N)
`
`16N
`
`THE JOURNAL OF NUCLEAR MEDICINE © Vol. 42 * No. 10 * October 2001
`
`
`
`
`

`

`High target-to-
`backgroundratio’
`
`Ease of
`preparation’®
`
`Fast liver
`clearance’
`
`.
`
`‘Ue
`
`Sereite(Tay
`diagnosis**
`
`BP) EOP)
`
`pall patients with known or suspected coronary artery disease,
`TBs
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`5
`if
`el M taken to ensure continuous cardiac monitoring FTO
`NatealoMUU TPM LUEMLecOlatLe!
`aaneve (erln(TOTTORIES MLLae
`eee
`© See Brief Summary of prescribing information on adjacent page.
`22001 Nycomed EU tela
`
`peca-tCeramicts
`
`TectinetiumcmTetrtosmin ForInjection
`
`PNTaACCCRC CRULi
`
`Ente iteliitate
`Tate
`solutions. Amersham
`Customer Service 800.292.8514
`bs
`:
`ter Pen
`
`
`
`
`

`

`MYOVIEW™
`—————ee
`BS-43-1011A
`MYOVIEW™
`ADVERSE REACTIONS
`Adverse events were evaluatedinclinicaltrials of 764 adults (511 men and 2:
`‘53 women)with
`a mean age of 58.7 years (range 29-94 years). The subjects received a mean
`dose of 7.67 mci
`on thefirst injection and 22.4 mCi on the second injection of Myoview™.
`Deaths did not occurduring theclinical study period of 2 days. Six cardiac deaths occurred 3
`days to 6 monthsafterinjection and were thoughtto be related to the underlying disease or car-
`diac surgery. After Myoview injection, serious episodes of angina occurredin 3 patients.
`Overall cardiac adverse events occurred in 5/764 (less than 1%) of patients after Myoview
`injection.
`The following events were noted in less than 1% of patients:
`Cardiovascular: angina, hypertension, Torsades de Pointes
`Gastrointestinal: vomiting, abdominal discomfort
`Hypersensitivity: cutaneous allergy, hypotension, dyspnea
`Special Senses: metallic taste, burning of the mouth, smelling something
`There wasa low incidence(less than 4%)of a transient andclinically insignificant rise in white
`blood cell counts following administration of the agent.
`DOSAGE AND ADMINISTRATION
`For exercise and rest imaging, Myoview is administered in two doses:
`Thefirst dose of 5-8 mCi (185-296 MBq)is given at peak exercise.
`The second dose of 15-24 mCi(555-888 MBq) is given approximately 4 hourslater, at rest,
`Imaging may begin 15 minutes following administration of the agent.
`Dose adjustment has not been established in renally orliver impaired, pediatric or geriatric
`patients.
`RADIATION DOSIMETRY
`
`pGy/MBq
`
`rad/mCi
`
`Kit for the Preparation of Technetium Tc99m Tetrofosmin for Injection
`Diagnostic Radiopharmaceuticalfor intravenous use only
`
`Rx ONLY
`Please consult full prescribing information before using. A summary
`follows:
`DESCRIPTION
`
`The Medi-Physics Myoview kit is supplied as a pack of five vials for use in the preparation
`of a technetium Tc99m tetrofosmin intravenous injection to be used for the scintigraphic delin-
`eation of regions of reversible myocardial ischemia in the presence or absence ofinfarcted
`myocardium. Eachvial contains a predispensed, sterile, non-pyrogenic, lyophilized mixture
`of 0.23 mg tetrofosmin [6,9-bis(2-ethoxyethyl)-3, 12-dioxa-6,9-diphosphatetradecane], 30 pig
`stannous chloride dihydrate (minimum stannous tin 5.0 1g; maximum total stannous and
`stannic tin 15.8 yg), 0.32 mg disodium sulphosalicylate and 1.0 mg sodium D-gluconate,
`and 1.8 mg sodium hydrogen carbonate. The lyophilized powderis sealed undera nitrogen
`atmosphere with a rubber closure. The product contains no antimicrobial preservative.
`CLINICAL PHARMACOLOGY
`General
`When technetium Tc99m pertechnetate is added to tetrofosmin in the presence of stannous
`reductant, a lipophilic, cationic technetium Tc99m complex is formed, Tc99m tetrofosmin. This
`complex is the active ingredient in the reconstituted drug product, on whose biodistribution and
`pharmacokinetic properties the indications for use depend.
`Clinical Trials
`A total of 252 patients with ischemic heart disease or atypical chest pain who had a reason
`for exercise stress imaging were studied in two open-label, multi-center,clinicaltrials of Tc99m
`tetrofosmin (study a and study b). Of these 252 patients there were 212 (B3%) males and 40
`(17%) females with a mean age of 60.5 years (range 33.7 to 82.4 years). At peak exercise, max-
`imum heart rate achieved and peak systolic blood pressure were comparable after Myoview and
`thallium-201 exercise studies.
`All patients had exercise and rest planar imaging with Myoview and thallium-201; 191 (76%)
`patients also had SPECTimaging. The Myoview andthallium-201 images were separated bya
`mean of 5.1 days (1-14 days before or 2-14 days after Myoview). For Myoview imaging, each
`patient received 185-296 MBq (5-8 mCi) Tc99m tetrofosmin at peak exercise and 555-888 MBq
`(15-24 mCi) Te99m tetrofosmin at rest approximately 4 hours later. For thallium-201 imaging,
`patients received thallium-201 55.5-74 MBq (1.5-2.0 mCi) at peak exercise.
`The images were evaluated for the quality of the image (excellent, good or poor) and the
`diagnosis (with scores of 0 = normal, 1 = ischemia, 2 = infarct, 3 = mixed infarct and ischemia).
`The primary outcome variable was the percentageof correct diagnoses in comparison to the
`tinal clinical diagnosis.All planar images wereblindly read; SPECT images were evaluated by
`the unblinded investigator. A subset of 181/252 (71%) patients had coronary angiography
`comparisons to the planar images of Myoview orthallium-201.
`INDICATIONS AND USAGE
`Myoviewis indicated for scintigraphic imaging of the myocardium following separate adminis-
`trations under exercise and resting conditions.
`It
`is useful
`in the delineation of regions of
`feversible myocardial ischemia in the presence or absence of infarcted myocardium.
`CONTRAINDICATIONS
`None known,
`WARNINGS
`In studying patients with known or suspected coronary artery disease, care should be taken
`to ensure continuous cardiac monitoring and the availability of emergency cardiac treatment.
`PRECAUTIONS
`General
`
`Based on humandata, the absorbed radiation doses to an average humanadult (70 kg) from
`intravenousinjections of the agent under exercise and resting conditions are listed in the fol
`lowing table. The valuesarelisted in descending order as rad/mCi and yGy/MBq and assume
`urinary bladder emptying at 3.5 hours.
`Estimated Absorbed Radiation Dose (Technetium Tc99m Tetrofosmin Injection)
`Absorbed radiation dose
`Exercise
`Rest
`rad/mCi
`
`Target organ
`pGy/MBgq
`48.6
`0.180
`33:2
`0.123
`Gall bladder wall
`30.4
`0.113,
`20.1
`0.075
`Upperlargeintestine
`19.3
`0.071
`15.6
`0.058
`Bladderwall
`22.2
`0,082
`15.3
`0.057
`Lowerlarge intestine
`17.0
`0.063
`12.1
`0.045
`Small intestine
`12.5
`0.046
`10.4
`0.039
`Kidney
`11.6
`0.043
`8.04
`0.030
`Salivary glands
`9.55
`0.035
`7.88
`0.029
`Ovaries
`8.36
`0.031
`7.34
`0.027
`Uterus
`5.58
`0.021
`6,23
`0.023
`Bone surface
`4,98
`0.018
`5.00
`0.019
`Pancreas
`4.63
`0.017
`4.60
`0.017
`Stomach
`5.83
`0.022
`4.34
`0.016
`Thyroid
`4
`0.015
`4.32
`0.016
`Adrenals
`3.93
`0.015
`4.14
`0.015
`Heart wall
`3.97
`0.015
`4.14
`0.015
`Red marrow
`3.82
`0.014
`4.12
`0.015
`Spleen
`3.22
`0.012
`3.52
`0.013
`Muscle
`3.05
`0,011
`3.41
`0.013
`Testes
`4.45
`0.015
`3.22
`0.012
`Liver
`254
`0.009
`3.11
`0.012
`Thymus
`2.15
`0.008
`2.72
`0.010
`Brain
`2,08
`0.008
`2.27
`0.008
`Lungs
`1.91
`“0.007
`2.22
`0.008
`Skin
`
`
`
`
`0.008 2.22 0.007Breasts 1.83a
`Dose calculations were performed using the standard MIRD method (MIRD Pamphlet No.1 (rev).Sociely
`ot Nuclear Medicine, 1976). Elfective dose equivalents (EDE) were calculated in accordance with ICAP 53
`(Ann. ICAP 18 (1-4),1988) and gave values of 8.61 x 10° mSV/MBq and 1.12 « 10° mSV/MBq after exercise and
`rest, respectively,
`
`To minimize radiation dose to the bladder, the patient should be encouraged to void whenthe
`examination is completed and as often thereafter as possible. Adequate hydration should be
`encouraged to permit frequent voiding,
`The contents of the Myoview vial are intended only for use in the preparation of technetium
`Te98m tetrofosmin injection and are NOT to be administered directly to the patient.
`As withall injectable drug products, allergic reactions and anaphylaxis may occur.
`Sometimes Tc99m labeled myocardial
`imaging agents may produce planar and SPECT
`images with different imaging information.
`
`Technetium Tc99m tetrafosmin injection,like other radioactive drugs, must be handled with
`care and appropriate safety measures should be used to minimize radiation exposureto clinical
`personnel. Care should also be taken to minimize radiation exposure to the patient consistent
`with proper patient management.
`Radiopharmaceulicals should be used by or under the control of physicians who are qualified
`by specific training and experience in the safe use and handling of radionuclides, and whose
`experience and training have been approved by the appropriate governmental agency autho-
`tized to license the use of radionuclides.
`DrugInteractions: Druginteractions were not noted and were notstudied in clinical studies in
`which Myoview was administered to patients receiving concomitant medication. Drugs such as
`beta blockers, calcium blockers and nitrates mayinfluence myocardial function and blood flow.
`The effects of such drugs on imaging results are not known.
`
`Carcinogenesis, Mutagenesis, Impairmentof Fertility
`Studies have not been conducted to evaluate carcinogenic potential or effects on fertility.
`Tetrofosmin sulphosalicylate was nol mutagenic in vitro in the Am
`es test, mouse lymphoma,
`or human lymphocyte tests, nor wasit clastogenic in vivo in the mo
`use micronucleustest.
`Pregnancy Category C
`Animal reproduction studies have not been conducted with Myoview,It is not known whether
`Myoview can causefetal harm when administered to a Pregnant womanor can affect reproduc-
`tive capacity. Therefore, Myoview should nat be administered to a Pregnant woman unless the
`potential benefit justifies the potential risk to the fetus.
`Nursing Mothers
`Technetium Te99m pertechnetate can be excreted in human mi
`ik. Therefore, formula should
`be substituted for breast milk until the technetium has cleared
`woman.
`from the body of the nursing
`Pediatric Use
`Safety and effectiveness in pediatric patients have not been established.
`
`Manufactured by:
`Nycomed Amersham plc
`Amersham United Kingdom
`
`Patent No. 5,045,302 (r)
`
`Distributed by:
`Medi-Physics,Inc.,
`Arlington Heights, IL 60004
`1-800-633-4123 (Toll Free)
`—_°—
`
`References: 1, Munch G, Neverve J, Matsunari |, Schroter G, Schwaiger M. Myocardial tech-
`netium-98m-tetrofosmin and technetium-99m-sestamibi kineticsin normal subjects and patients
`with coronary artery disease, J Nucl Med. 1997-38:428-432. 2. Higley B, Smith FW, Smith Ti
`et al. Technetium-99m-1 ,2-bis(bis(2-ethoxyethyl) phosphino] ethane: human biodistribution,
`dosimetry and safety of a new myocardial perfusion imaging agent. J Nuc! Med 1993;34;30-38.
`3. Jain D. Technetium-99m labeled myocardial perfusion imaging agents. Semin Nucl Med
`1999;29:221-236. 4. MYOVIEW™ Prescribing Information.
`
`Revised December 1998
`
`Myoview is a trademark of Nycomed Amersham ple.
`BS-43-1011A
`
`VAlmersham HEALTHCARE
`
`
`
`
`

`

`Unexpected Shortfalls
`(Continued‘from page 16N)
`
`|
`
`erofmanufacturing from Bristol-Myers Squibb,
`two separate sets of ensuing eventsled to the
`interruptions in production. Kevin Brooks,
`Bracco’s Senior Director, Nuclear Medicine,told
`Newsline that Braccoinstituted careful and
`detailedplanning measures more than 4 years ago
`ensure continued availability of Kinevac and
`Choletec during the transfer.
`Inthe case ofKinevac, the standing New Drug
`Application (NDA) was more than 20 yearsold
`andrequired an update to someofthe manufac-
`turing and testing processes to reflect 2001
`Food and DrugAdministration (FDA) standards.
`Brooks reported, “We unfortunately experienced
`costly delays, some of which were unexpected
`and outside our control, that have created the
`current Kinevac productshortage.” The company
`iscurrently working toward completing the
`technology transfer and submitting the supple-
`mental NDA.“We havenotified and are working
`with the FDA regarding the Kinevacsituation,”
`says Brooks.
`The delay in the transfer of Choletec manu-
`facturing came as a more abruptsurprise to
`Bracco. A new raw material source and a backup
`source had been identified. According to Brooks,
`Bracco investigated both sources with due
`diligence procedures and put the first-choice
`Source through a pilot program to ensure pro-
`duction capabilities. In April 2001, however, the
`pimary raw material supplier abruptly shut down
`synthesis operations, which were unrelatedto the
`nuclear medicine product category. The secondary
`supplier, now the only source of mebrofenin, was
`_ Stilindevelopment, Batchstability and otherdata
`ae-currently being compiled for FDA Current
`Good Manufacturing Practices (CGMP)approval,
`Which will not be forthcoming untilat least spring
`2002. Ifapproval is granted at that time, Choletec
`ies be available againin the third quarter of
`
`'
`
`_
`
`The Impactof Shortages
`During the past year, the nuclear medicine
`“ommunity has dealt with a similar unexpected
`tee of“Co B12. In the summerof2000,
`sil Supplier of *’Co announced ona
`aa that production ofthe 270-day half-life
`aWould ceasethe following Monday. Many
`s oan wereable to stretch their supplies
`2
`liberstein notes, “We'relucky “’Co has
`ong half-life.” A new supplier is now
`
`producing radiolabeled B12, and the FDA has
`approved the supplemental NDA. Bracco antic-
`ipates that the product, Rubratope, will be
`available for sale in October 2001.
`Silberstein cautions against blaming pharma-
`ceutical companiesdirectly for such shortfalls.
`“Because the manufacturers were caught by
`surprise from their own suppliers, whom they
`thought they knew well in several instances, we
`can’t blame them,” hesays.
`Bracco has assured the nuclear medicine
`community that both Kinevac and Choletec
`will return to the market as soonas possible, given
`the constraints of manufacturing difficulties
`and FDA regulations. Disofenin (Hepatolite)
`remains on the market for hepatobiliary imaging,
`butit, too, has been reported to be in short
`supply.
`In the interim, some nuclear medicine physi-
`cians worry about the effects on practice, patient
`care, and perceptionsofthe field. Even the search
`for temporary substitutes may be damaging.“It
`maybepossibleto derive other proceduresto sub-
`stitute for Kinevac, such as a standardized fatty
`meal, and to find other compounds capable of
`doing whatthe presentbiliary scanning agents
`do to delineate the dynamics of hepatobiliary
`function,” says Beven. “But it would take sub-
`stantial time to documentthe reliability of such
`agents,and, by the timethey are available, other
`alternatives would be so firmly incorporated into
`the practice patternsofreferring physiciansthat
`the new radionuclide procedures would be of
`no interest to them.”
`The need for speed is clear. “The SNM
`Committee on Radiopharmaceuticals is urging
`radiopharmaceutical manufacturers to have a
`secondary source of drug available—but that is
`clearly not alwayspractical,”said Silberstein. “We
`are also contacting the FDAto indicate the urgent
`need for these materials as quickly as possible.”
`Newslinewill keep readers updatedon these
`andanyothershortfalls in radiopharmaceuticals
`andrelated products. The Committee on Radio-
`pharmaceuticalswill continue to post news,
`updates, and action items on the SNM Web
`site at www.snm.org. The SNM Ambulatory
`PaymentClassification Task Force regularly
`updates reimbursement informationonthesite.
`On September13, a revised chart ofradiophar-
`maceuticals and drugs eligiblefor continued
`separate Medicare payment was posted.
`
`ANITSMAN
`
`Newsline
`
`19N
`
`
`
`
`