Volumeflgzi
`
`Number 10
`
`October 2001
`
`bemoan-1.20111
`
`'
`
`HEALTH SCIENCES '
`LIBRARIES
`
`TheJournal of
`Nuclear Medicine
`
`l
`
`ll1l1 1 l l
`
`l i
`
`The Official Publication
`of the Society of Nuclear Medicine, Inc.
`
`MAIA Exhibit 1031
`
`MAIA V. BRACCO
`
`IPR PETITION
`
`
`
`
`MAIA Exhibit 1031
`MAIA V. BRACCO
`IPR PETITION
`
`

`

`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 may be repro-
`duced or translated without permission from the copy-
`right owner. Because the copyright on articles published in
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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-
`loading: www.3nm.org.
`
`THEJOURNAL OF NUCLEAR MEDICINE (ISSN 0161-
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`Publications Committee
`R. EDWARD COLEMAN, MD
`Chairman
`ELIAS H. Borvmicx, MD
`SIMINDOKH'I‘ DADPARVAR. MD
`SUSAN A. GILBERT. CNMT
`STANLEY J. Gomsmrrn. MD
`MICHAEL M. GRAHAM. MD. PHD
`MARK W. Gaocti. PHD
`MILTON J. GUIBERTEAU. MD
`HEINRICH SCHELBERT. MD, PHD
`ARNOLD M. STRASHUN. MD
`H. WILLIAM STRAUSS, MD
`KATHY S. THOMAS. CNMT
`RONALD S. Tntorsxv, PHD
`DAVID A. WEBER. PHD
`
`Ex ofiicio
`ROBERT F. CARRETI‘A. MD
`CONRAD E. NAGLE. MD
`
`Senior Journals Manager
`BRIAN HAers
`
`Associate Director of Publications
`SUSAN ALEXANDER
`Senior Editors
`SUSAN NADOLNY
`TERRY PEARSON
`
`WILLIAM J. BenTssA
`
`Marketing Manager
`JENNIFER ZAWACKI
`
`Graphic Artist
`JEN NIFER GILBERTSON
`
`Production Manager
`STEVEN KLEIN
`Production Assistant
`TINA PAxTON
`Director of Publications
`MELISSA MCKENNA
`Executive Director
`
`
`
`
`

`

`I l
`
`1457 99mTc-Sestamibi Retention Characterising
`During pharmacologic Hyperernia in Human
`Myocardium: Comparison with Coronary Fl
`Reserve Measured by Doppler Flowire
`Junichi Taki, Suxumu Fujino, Kenichi Nakajima,
`lcliim Marsmmri. Hiderilri Okazaki. Takaslzi Saga.
`Hisaxhi Bunko, and Nm‘ihisa Twiami
`
`1464 Clinical Impact of 13F-FDG PET in Thyroid
`Carcinoma Patients with Elevated Thyroglubulin '
`Levels and Negative 13‘! Scanning Results
`After Therapy
`Badia 0. Halal, Pascal Merle-'1,
`
`I l
`
`
`
`I I
`
`I
`
`|I
`
`Mw‘iewElisabelh Taliban. Brigitte Franc,
`Claire Sc'lwnrlz. Haléne Gaulhier-Knelesnikov.
`Alain Prigem. and André Sylvia
`
`1470 Serum Thyroglobulin Concentrations and
`131I Whole-Body Scan Results in Patients
`with Differentiated Thyroid Carcinoma After
`Administration of Recombinant Human Thyroid-
`Stimulating Hormone
`Almsia David. Annabella Blorra. Marta Bondanelli,
`Robrrm Rossi. Elia Roll, Lewis E. Braverman,
`
`Lui'iww BllSltlii. (mt! Error-e C. degll Uberii
`
`1476 Expression of Multidrug Resistance Protein
`and Messenger RNA Correlate with 99mTc-Illllil
`Imaging in Patients with Lung Cancer
`Jinslian erau. Koran) Higaxhi, Yoshimichi Ueda‘
`Villa) Kmicrmcl. Dtii'llttun Gun, Fulfil/CU Jisalti,
`
`Ayn Stiklli'flfl Tmmmn Takegami, Shogo Kallufl'fl
`mid lrum Yimmmrim
`
`1484 Determination of Glomerular Filtration Rate
`
`by Means of Newly Developed Plastic
`Scintillation Counter Both With and
`Without Dilution Procedures
`Kaznn lrnl;
`
`1489 Comparison of [13F]FDG PET and 2°1Tl SPECT in
`Evaluation of Pulmonary Nodules
`Kmart] Higcrrhi, I’nshimichi Urda. TmrnmuSnklrijflli.III
`Himyasu Saki. M(H’I£ilJLi Ogurhi. Mirsilru Tamgm
`.S'uzuku Taki, Himu Tommi. Sham; Kamlda.
`and Hum I’amamoro
`
`1 497 Invited Commentary: Changing Pattern of
`Lung Cancer and Its Imaging: 2:11-11 SPECT
`Versus [13F]FDG PET
`Kazan Kulmla
`
`CONTINUING EDUCATION
`
`1 499 Technical Aspects of Myocardial SPECT'
`Guido Germano
`DJ
`
`|'
`I
`
`magi"!
`
`Volume 42, Number 10 0 October 2001
`
`
`
`\ O
`
`fficial Publication of
`the Society of Nuclear Medicine
`
`i4“
`
`16H
`
`25H
`
`25H
`
`26H
`
`28H
`
`Public Affairs Update
`William Ufirlman
`
`Unexpected Shortfalls of Two Nuclear Medicine
`Pharmaceuticals
`
`SNM Executive Director Search
`
`Keep in Mind
`
`Loevinger—Berman Award Presented to Keith F.
`Eckerman
`
`In Memoriam: Richard Lambrecht, PhD.
`1943-2001
`Mathew L. Tll(il\'IU'. PliD
`
`30H
`
`SNM Announces Education Initiatives
`
`32M
`
`34H
`
`Basic Science CD-ROM: Filling a Need, Fulfilling
`a Mission
`
`SNM Issues Two New Volumes in Nuclear
`
`Cardiology Self-Study Series
`
`37N
`
`Newsbriefs
`
`38N
`
`Erratum
`
`CLINICAL INVESTIGATIONS
`
`1441 Donepezil Hydrochloride Preserves Regional
`Cerebral Blood Flow in Patients with
`Alzheimer‘s Disease
`
`Seign Nuktuitr Triknslii Armin. Hires/ii Malinda.
`Muscimke Urm. and Mumru Talcumki
`
`1446 Fractal Analysis of Cerebral Blood Flow
`Distribution in Alzheimer’s Disease
`Michinolm Nagan, Kenya Mal-axe, Takarmri Kikm'lii,
`Marimba lkrdu. Akilllko Nylm. Ryuji Fukuhura,
`Yoshifumi Sngawmn. Himshi Miki, and Junpei lkezoe
`
`1451 Clinical Impact of Combination of Scatter,
`Attenuation Correction, and Depth-Dependent
`Resolution Recovery for 2°ITI Studies
`Francois Hal-cl, Rémi Gém'n, Dcumil Daau,
`Rachida Lebmhi. Nicolas Delahaye, Badia 0. Halal,
`Dominique Le Guludec, and Marc Fai‘aggi
`———__
`
`
`
`
`

`

`1551
`
`FDG Uptake and Glucose Transporter Subtype
`Expressions in Experimental Tumor and
`Inflammation Models
`
`1 556
`
`1 563
`
`1571
`
`Takafumi Mochiznlci, Erika Tsukamoto, Fuji Kuge,
`Kakako Kanegae, Sonji Zhao. Kenji Hikosaka.
`Mama Hosokawa, Masashi Kohanawa,
`
`and Nagara Tamaki
`
`Quantification of Serotonin Transporters
`in Nonhuman Primates Using [‘23I1ADAM
`and SPECT
`
`Paul D. Acton, Seek-Rye Chai, Catherine Hon.
`Karl Pla'ssl, and Hank F. Kung
`
`Registration of Emission and Transmission
`Whole-Body Scintillation-Camera Images
`Katarina Sjfigreen. Michael Ljungberg, Karin Wingiirdlz,
`Kjell Erlandsson. and Sven-Erik Strand
`
`Accuracy of Ventricular Volume and Ejection
`Fraction Measured by Gated Myocardial SPECT:
`Comparison of 4 Software Programs
`Kcniclii Nalcajima. Takaltiro Higuchi. Junichi Taki,
`Masaya Kuwaiti), and Norihisa Tanami
`
`1579
`
`Phantom Studies for Estimation of Defect Size
`on Cardiac 1"F SPECT and PET: Implications
`
`for Myocardial Viability Assessment
`t'cltira Matsnnari, Tatsnya Yaneyama,
`
`Sugaka Kanayama, Masamit'lti Matsudaira.
`Karachi Nakajima. Janichi Talci. Stephan G. Nekolla,
`Nai'ihisa Tanami. and Kinichi Hisacla
`
`DEPARTMENTS
`
`1586
`
`Book Review
`
`1587
`
`Letters to the Editor
`
`1590
`
`Calendar
`
`40A
`
`44A
`
`Classified Advertising
`
`JNM Direct Response
`
`BASIC SCIENCE INVESTIGATIONS
`
`I 1508 High-Level Production of oz-Particle—Emitting
`I
`211At and Preparation of 211At-Labeled
`Antibodies for Clinical Use
`Michael R. Zalutsky, Xiao-Gaang Zhao. Kevin L. Alston,
`and Darrell Bigner
`
`I |
`
`I 1516 Invited Commentary: Overcoming the Obstacles
`to Clinical Evaluation of NAP-Labeled
`Radiopharmaceuticals
`D. Scott Wilbur
`
`‘
`‘
`I
`
`‘ 1519 MTG-Labeled Divalent and Tetravalent 0049
`Single-Chain Fv's: Novel Imaging Agents for
`Rapid In Vivo Localization of Human Colon
`Carcinoma
`
`Apallina Gael. Janina Saranokaa-Kortvlewicz.
`Steven H. Hinriclts, James Wistccarver.
`
` 1528 Invited Commentary: Multivalent Single-Chain
`
`I.
`
`Gabriela Pat'linlcava. Sam Augustine. David Colclwr.
`Barbara JM. Booth, and Snrinder K. Barra
`
`Antibodies for Radioimaging of Tumors
`
`i
`
`Eyed VS. Kashmiri
`
`i 1530 Conjugation with 111In-DTPlt-PolydEthylene
`Glycol) Improves Imaging of Anti-EGF Receptor
`Antibody 0225
`Xiaoxia Wen, Qing-Ping Wu. Slti Ky. Lee Ellis:
`Clmsilp Chat'ns'angavaj. Abraham S. Delpasxaml.
`Sidney Wallace. and Chan Li
`
`I
`
`1538 Comparative Cellular Catabotism and Retention
`of Astatine-, Bismuth-, and Lead-Radiolabeled
`Internaiizing Monoclonal Antibody
`Zliengrheng Yaw. Kaylran Garmmtani. Karen J. Wang,
`Luke 5. Park. Ekaterina Dadm'ltm'a.
`Alexander Yardrmot', Thomas A. Waldimmn.
`
`William C. Et'ltelman. Chang H. Paik.
`and thrga A, Carratquilln
`
`i 1 I
`
`I
`
`_.
`i
`
`I
`
`1545 High—Dose Treatment with 186Re-HEDP or
`‘flSm-EDTMP Combined with Amifostine in
`a Rabbit Model
`
`Winfried Brenner. Willm Uwe Kampen.
`Corinna van Farstner. Corinna Briimmc’r.
`Man: Zultaym. Claus Maltlt’. NUI‘b‘f’" CUT,"
`and Eberhard Heine
`
`jnm.snmjournals.org
`
`Continuing Education Activity
`www.snm.org/educationlce_online.html
`
`Newsline Online
`
`www.cnm.org/about/news_order.html
`
`
`
`
`

`

`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.
`During the first week ofthat month, Btacco 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 WTc-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-order situation is the result
`
`of issues encountered during a change in manu-
`facturers.“ wrote Meeks. “Bracco is committed
`to resolving this situation as soon as possible."
`The letter also noted that a rationing program
`would be used to distribute the remaining inven-
`tory ofKincvac during the month ol'August. Cus-
`tomers who purchased Kinevac directly from
`Bracco were allowed to place one order for a max-
`imum ot‘two boxes ofKinevac. Radiopharma»
`ties with average monthly orders larger than two
`boxes per month ol‘Kinevae over 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 September 1.
`In the second letter, dated August 7. Adrian
`Trcvisan, Product Manager, Nuclear Medicine
`at Brae-co, 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 one of the raw
`material providers.
`
`The Nuclear Medicine
`
`Community Reacts
`Reaction among nuclear medicine practition-
`ers was one of dismay. as emails and phone calls
`about rationing, shortfalls, and possible alterna-
`tive pharmaceuticals circulated among
`practitioners and Society of Nuclear Medicine
`(SNM) officers and staff. 011 August 10, Edward
`B. Silberstcin, MD, Chair of the SNM
`Committee on Radiopharmaceuticals, talked
`with Bracco representatives and issued a
`statement on behalfofthe committee. “The good
`news is that this radiopharmaceutical shortfall
`was not a direct business decision to cut pro-
`duction of materials with a 10w profit margin,“
`said Siiberstein.
`
`The bad news, of course, was that shonages
`would cause inconveniences to practitioners and
`could affect the quality of patient care in some
`facilities. The experience ofTerence Eleven, MD,
`Director ofNuclear Medicine at Our Lady
`ofthe 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 1-month supply ofKinevac." he noted
`in mid September. “Since that time we have
`obtained about a l-year supply from a number of
`different sources. Not being able to meet the
`demand for these procedures would have an
`adverse impact on our credibility as nuclear
`medicine physicians and cause a loss of interest
`in the specialty in the eyes ofreferring physicians,
`particularly those specialists who have learned i0
`depend on these procedures as a significant p311
`oftlieir patient management."
`
`.
`Different Reasons for Shortfalls
`With the two announcements coming with“
`a span 0% days, the immediate assumption in the
`nuclear medicine community was that the
`shortfalls Were related. In fact, although both
`pharmaceuticals were in the middle of a trans—
`(Comimied on page ”W
`
`IGN
`
`THE JOURNAL or NUCLEAR Maoicuvr. - Vol. 42 - No. 10 - October 2001
`
`
`
`
`

`

`High target-to-
`background reflex"4
`
`Ease of
`|:)re|:u:1rctI'ion"3
`
`Confident
`diagnosis“
`
`Excellent image
`
`TechnefiumTcQQmTetrotosminForlnjection
`
`5.? ASS-00.3.2019
`
`[Spitting patients with known or suspected coronary artery disease
`t‘v Shetttd tze taken to ensure continuous cardiac monitoring and the
`i‘ilf-id‘i'lw, E” Blttereenw Cardiac treatment. As with an iniectabte drug
`., JtUC s. al-ergm reactions and anapttytaxis may occur.
`Plea
`( I
`.
`Q9 “Le Brier SUmmary 01 prescribing information on adtacem page
`£255” Nyccmed Anieistiom
`
`MYOVIEW. A clear message from the heart.
`
`Nycomed
`_
`sun-nous. Amersham
`
`Customer Service 800.292.8514
`.us-nai.com
`
`
`
`
`

`

`MYOVIEW"
`
`35413-1 011A
`
`MYOVIEW'"
`4—————________
`ADVERSE REACTIONS
`
`Kit for the Preparation of Technetium TcSllm Tetrofosrnin for Injection
`Diagnostic Radlopharmaccutical tor Intravenous use only
`
`Rx ONLY
`Please consult full prescribing Information before using. A summary
`follows:
`DESCRIPTION
`
`The Marti-Physics Myovi‘ew kit is supplied as a paclt at live vials for use in the preparation
`01 a technetium Tcsgm lelrofosmin intravenous injection to be used for the scintigraphr'c delin-
`cation 01 regions oi reversible myocardial lschemla In the presence or absence of infarcted
`myocardium. Each vial contains a predispensed. sterile. non-pyrogenic. lyophilized mixture
`of 0.23 mg letrolosrnin [6.9-hile-ethexyethyIJ-a.12-clove-6.9—diphosphaletredecanej. 30 pg
`stannous chloride dihydrate (minimum standous tin 5.0 No: maximum total stanrtous and
`stannlr tin 15.3 pg}. 0.32 mg disodium sulphosalicylate and 1.0 mg sodium D-gluconate.
`and 1.3 mg sodium hydrogen carbonate. The lyophilized powder is sealed under a nitrogen
`atmosphere with a rubber closure. The product contains no antimicrobial preservative.
`CLINICAL PHARMACOLOGY
`General
`When technetium T099rn pertechnetale is added to tstrofosmin in the presence of slannous
`reductant. a fipophilic, cationic technetium Tcsem complex is formed. Tagger tetroioemin. This
`complex is the active ingredient in the reconstituted drug product. on whose ‘ciodietrihution and
`pharmacokinelic properties the indications for use depend.
`Clinical Trials
`A total of 252 patients with isohemic hean disease or atypical chest pain who had a reason
`lor exercise stress imaging were studied in two open-label, multl-oenter. clinical trials of ‘l'c99m
`tetroiosrnin (study a and study bl. 01 these 252 patients there were 212 (33%) males and 40
`[17%) Iemales with a mean age of 60.5 years (range 33.711: 02.4 years). At peak exercise. max—
`imum hean rate achieved and peak systolic blood pressure were comparable alter Myoview and
`thallium—201 exercise studies.
`All patients had exercise and rest planar imaging with Myovlew and thallium-201: 191 (76%]
`patients also had SPECT imaging. The Myoview and thallium-201 images were separated by a
`mean 01 5.1 days (144 days before or 2-14 days alter Mycwiew}. For Myoview imaging, each
`patient received 185-296 MBq (5-3 mCij Tcssm letrolosrnin at peak exercise and 555-008 0130
`(15-24 mCi] Tchm letrolosmin at rest approximately 4 hours later. For thallium-201 imaging.
`patients received thallium-201 55.544 160:: (Ls-20 mail at peak exercise.
`The images were evaluated lcr lhe qualily oi the image (excellent, good or poor) and the
`diagnosis (with scores 010 = normal. 1 = iechemla. 2 = iniarct. 3 = mixed iniarct and ischemia).
`The primary outcome variable was the percentage of correct diagnoses in comparison to the
`linal clinical diagnosis. Ali planar Images were blindly read: SPECT images were evaluated by
`the unbllnded Investigator. A subset of 180252 (71%) patients had coronary angiography
`comparisons to the planar images 01 Myoview or thallium-201.
`INDICATIONS AND USAGE
`Mycview is indicated lor scinligrapnic imaging 01 the myocardium lollowrng separate adminis-
`trations under exercise and resting conditions.
`It
`is useful
`in the delineation of regions of
`reversible myocardial ischemia in the presence or absent» 01 inlarcled myocardium.
`CONTRAINDICATIONS
`None known.
`WARNINGS
`In studying patients with known or suspected coronary artery disease, care should be taken
`to en sure continuous cardiac monitoring and the avarlability of emergency cardiac treatment.
`PRECAUTIONS
`General
`
`To minimize radiation dose to the bladder. the patient should be encouraged to void when the
`examination is completed and as often tharealler as possible. Adequate hydration should be
`encouraged to permit Ireouenl voiding.
`The contents oi the Myoview vial are intended only for use in the preparation at technetium
`Tcsstm telrofosmin injection and are NOT lo be administered directly to the patient.
`As with all injectable drug products, allergic reactions and anaphylarris may occur.
`Sometimes TcQQm labeled myocardial
`imaging agents may produce planar and SPECT
`images with different imaging inlormation.
`
`live drugs, must be handled with
`Technetium rcssm lelroiosmln injection. like other radio
`care and appropriate Safety measures should be used to minimize radiation exposure to clinical
`personnel. Care should also be taken to minimize radiation exposure to the palienl consistent
`with proper patient management.
`Fladiopharmaceuticals should be used by or under the control of physrcians who are qualiliod
`by specific training and experience in the safe use and handling ol radionuclide: and whose
`expensnce and naming have been approved by the appropriate governmental agency autho-
`rized to license the use at rarl'ronuclides.
`Drug interactions: Drug Interactions were not noted and were not studied in clinical sludies in
`which Myoviaw was administered to patients receiving concomitant medication. Drugs such as
`beta blockers. calcium blockers and nitrates may influence myocardial lunc1ion and blood liow.
`The elfecls at such drugs on imaging results are not known.
`
`Carcinogenesis. Mutagenesis. impairment of Fertility
`Studies have not been conducted to evaluate carcinogenic potential or effects on fertility.
`Tetrolosrnin sulphoealicylate was nol mulagenic in wire in the Am
`as test. mouse lymphoma.
`or human lymphocyte tesls. nor was it clastogenic in vivo in the mo
`use micron ucleus test.
`Pregnancy Category C
`Animal reproduction studies have not been conducted with M
`it is not known whether
`yoview.
`Myoview can cause telal harm when administered to a
`pregnant woman or can ailect reproduc-
`live capacity. Therelore. Myoview should not be admin
`islered to a pregnant woman unless the
`potential benelit justiiles the potential risk to the talus.
`Nursing Mothers
`Technerium Tc9§m partechnetale can be excreted In human m
`ilk. Therefore. formula should
`be substituted for breast milk until the technetium has cleared
`woman.
`from the body 01 the nursing
`Pediatric Lise
`Saiety and attentiveness in pediatric patients have not been established.
`
`Adverse events were evaluated in clinical trials or 764 adults [511 men and 253 Wflmanlwlth
`u mean age of 50.7 years (range 29-94 years). The subjects received a mean dose 01137 mCi
`on the first injection and 2.4 m01 on the second injection 01 Mywieww_
`Deaths did not occur during the clinical study period of 2 days. Six cardiac deaths occurreda
`days to 6 months after Injection and were thought to be related to the underlying diseaseor car-
`doc surgery. After Myoview injection. serious episodes of angina declined in 3 panama
`Overall cardiac adverse events occurred in 5.764 {less than 1%] of patients alter Mm...
`injection.
`The following events were noted in less than 1% of patients:
`Cardiovascular: angina, hypertension. Torsades de Poinlas
`Gastrointestinal: vomiting. abdominal discomfort
`Hypersensitivity: cutaneous allergy, hypotension. dyspnea
`Special Senses: metallic taste. hunting of the mouth. smelling something
`There was a low incidence {less than W.) of a transient and clinically insignificant rise in wh‘ne
`blood cell counts lollowing administration of the agent.
`DOSAGE AND ADMINISTRATION
`For exercise and rest imaging. Myovlow is administered in two doses:
`The first dose of 5-8 mCi [185-290 Mqu is given at peak exercise.
`The second dose of 15-24 rnGi (555-888 M80) is given approximately 4 hours Eater, at rest.
`Imaging may begin 15 minules lollowing administration oi the agent,
`Dose adjustment has not been established in renally or liver impaired. pediatric or geriatric
`patients.
`RADIATION DOSIMETRV
`
`Based on human data. the absorbed radiation doses to an average human adult (70 kg) from
`intravenous injections 0! the agent under exercise and resting conditions are listed in the lol-
`lowing table. The values are listed in descending order as tad/mCI and uGyi’MBq and assume
`urinary bladder emptying at 3.5 hours.
`Estimated Absorbed Radiation Dose (‘l’echnetium Tcsem Tetrolosmln injection)
`Absorbed radiation dose
`Exercise
`Fleet
`Target organ
`radJ'rnCi
`pGyl‘MBq
`redl'mCi
`pGyi’MBq
`
`Gall bladder wall
`0 120
`33.2
`0.130
`48.6
`Upper large intestine
`0.075
`20.1
`0.113
`30.6
`Bladder well
`0058
`15.6
`0.071
`193
`Lower large intestine
`0,057
`15.3
`0.002
`222
`Small inlestine
`0.045
`12.1
`0.063
`17.0
`Kidney
`0.039
`10.4
`0.046
`12.5
`Salivary glands
`0.030
`6.04
`0.043
`11.5
`Ovaries
`0.029
`7.013
`0.035
`9.55
`Uterus
`0.027
`7.34
`0.031
`8.36
`Bone surface
`0.023
`6.23
`0.021
`5.58
`Pancreas
`0.010
`5.00
`0.018
`4-98
`Stomach
`0.011
`160
`0.017
`11.53
`Thyroid
`0.016
`4.34
`0.022
`5.03
`Adrenals
`0.016
`d.32
`0.015
`4.11
`Heart wall
`0.015
`4.14
`0.015
`133
`Red marrow
`0.015
`4.14
`0.015
`3.97
`Spleen
`0.015
`4.12
`0.014
`3.32
`Muscle
`0.013
`3.52
`0.012
`3.3?
`Testes
`0.013
`3.41
`0.011
`305
`Over
`0012
`a 22
`0.015
`4‘15
`Thymus
`0.012
`3 11
`0.009
`2.54
`Brain
`0.010
`2.72
`0.008
`2.15
`Lungs
`0.000
`2.27
`0.008
`2.08
`Skin
`0.003
`2.22
`- 0.007
`1.91
`Breasts
`0.005
`2.22
`0.00?
`1.55
`—i————_——
`Dose calculations were parlor-med using the standard MIRD method [MIFiD Pamphlfll Not transmit
`“I "WWW MNICIWI 197E} Eflecllve dear: equivalents (EOE) were calculated in accordance with “3” 53
`Win ICRP ‘8 ll-tiJJBBBl and gave values of 3.61 :10’mSWMEq and 1 12 x to: mswuleq alterarercisaand
`rest. respectively
`
`Manufactured by:
`Nyoorned Amersham pic
`Am-rsham United Kingdom
`
`Patent No. 5.045.302 (1}
`
`Distributed by:
`Merit-Physics. Inc..
`Arlington Heights. It. 60004
`1-000-633-4123 (Toll Free}
`————————__———-—'
`
`Relerences: 1. Manon G, Neverve .J. Matsunari I. Sch oter G. Schwaiger M. Myocardial le‘h‘
`netium-BQm-tetroiosrnrn and technelium-Qan-seslamihr kinetics in normal subjects and patients
`with coronary anery disease. J Nuci Med. 1997;38:128-432. 2. Higley 5- Smith FW. 5mm] T'
`at al. Technelium-QQm-1.2-bislbis(2-elhoxyethyll phosphino] ethane: human biodislrrbullofl-
`dosimetry and solely ol 2 new myocardial perfusion imaging agent. J Nuci Med 1893;341:3033-
`3. Jam D. Technetiurn-QSm labeled myocardial perfusion imaging agents. 59min Mad Mad
`1999291221236. 4. MYOVIEW" Prescrrbing Information.
`
`Revised December 1998
`
`Myoview is a trademark ol Nyoomed Amsreham pic.
`35-43-1011A
`
`”Imersham HEALTHCARE
`
`
`
`
`

`

`Unexpected Shortfalls
`{Continuedfrom page 161V)
`
`ferofmanufacmring fi‘om Bristol-Myers Squibb,
`two separate sets of ensuing events led to the
`interruptions in production. Kevin Brooks,
`Becco’s Senior Director, Nuclear Medicine, told
`Newsline that Bracco instituted careful and
`detailed planning measures more than 4 years ago
`to ensure continued availability of Kinevac and
`Choletec during the transfer.
`Inthe case ofKinevac, the standing New Drug
`Jtirilrlication (NDA) was more than 20 years old
`and required an update to some of the 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
`cun‘ettt Kinevac product shortage." The company
`is currently working toward completing the
`technology transfer and submitting the supple-
`mental NDA. “We have notified and are working
`with the FDA regarding the Kinevac situation,”
`says Brooks.
`The delay in the transfer of Choletec manu-
`facturing came as a more abrupt surprise to
`Bmcco. 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
`SUUrce through a pilot program to ensure pro-
`duction capabilities. In April 2001 . however. the
`P1211131)! raw material supplier abruptly shut down
`Stilthettis operations. which were unrelated to the
`nuclear medicine product category. The secondary
`Supplier, now the only source of mebrofenin, was
`Slill in development. Batch stability and other data
`are currently being compiled for FDA Current
`Good Manufacturing Practices (cGM P) approval,
`Wl'thh will not be forthcoming until at least spring
`2ll02_ Ifapproval is granted at that time. Choletcc
`ESE? be available again in the third quarter of
`
`-
`
`-
`
`.
`
`_
`
`The Impact of Shortages
`Dunng the past year, the nuclear medicine
`Community has dealt with a similar uneXPECted
`slhortage of57Co 812. In the summer of 2000,
`lFrtdenaJor supplier of “Co announced on 3
`M03? that productlon ofthe 270-day half-life
`practif'would ceasethe following Monday. Many
`and, filings were able to stretch their supplies
`a l
`t crstein notes, “We’re'lucky 57CD has
`ORB 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 companies directly 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,” he says,
`Bracco has assured the nuclear medicine
`
`community that both Kinevac and Choletec
`will retum to the market as soon as possible, given
`the constraints of manufacturing difficulties
`and FDA regulations. Disofenin (Hepatolite)
`remains on the market for hepatobiliary imaging,
`but it, 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 perceptions ofthe field. Even the search
`for temporary substitutes may be damaging. “It
`may be possible to derive other procedures to sub-
`stitute for Kinevac, such as a standardized fatty
`meal, and to find other compounds capable of
`doing what the present biliary scanning agents
`do to delineate the dynamics of hepatobiliary
`function,” says Beven. “But it would take sub-
`stantial time to document the reliability of such
`agents. and, by the time they are available, other
`alternatives would be so firmly incorporated into
`the practice patterns of referring physicians that
`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 availablwbut that is
`clearly not always practical.“ said Silberstcin. “We
`are also contacting the FDA to indicate the urgent
`need for these materials as quickly as possible.“
`Newsline will keep readers updated on these
`and any orbcrshorfiiriis in imiiophar'itrucetriiccib
`and related products. The Committee on Radio-
`pl'rurmac'etrricriis wiN continue to post news,
`updates, and action items on the SNM Web
`site at wwwsmn. org. The .S‘NM .4 mbuiariorv
`Payment Ciasstj‘i'catiou Task Force regularly
`updates reimbursement iiyformariou on the site.
`On September 13, a revised chart ofmdiophar—
`mucenticais and drugs eligibiefor continued
`separate Medicare payment was posted.
`
`EINI'ISMEIN
`
`Newsline
`
`19N
`
`
`
`
`