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Dual Tracer
     Single Acquisition
          Imaging
                 Thomas F Heston, MD

   Medical Director of Nuclear Medicine, Family Care Network,
     Bellingham, Washington. Assistant Professor of Radiology
(Adjunct), Johns Hopkins Hospital, Baltimore, Maryland. Presented
 at the Missouri Valley Chapter of the Society of Nuclear Medicine
      33rd Annual Meeting, 2011, Lake of the Ozarks, Missouri
Conflicts of Interest




       None
Learning Objectives
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pro and con
●
    Conclusions
Dual Tracer Single Acquisition
●
    Historical background: pre-2000
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
DISA: Gastric Emptying
●
    1974: RC Heading
    ●
        Cornflakes and milk meal
    ●
        Liquid Phase: 200 uCi In-113m DTPA
    ●
        Solid Phase: ~ 30 pieces of filter paper, 3mm
        square, impregnated with 200 uCi Tc-99m
        sulphur colloid, coated with a thin film of
        perspex (poly methyl methacrylate)
    ●
        Conclusion: solid & liquid components of
        emptying differ, and may be relevent
        clinically after gastric surgery
DISA: Liver Scans
●
    1976: Buraggi et al
●
    Ga-67
    ●
        3 mCi 48 hours prior to imaging
    ●
        Concentrates in areas of inflammation and
        rapid cell division
●
    Tc-99m sulfur colloid
    ●
        1 mCi 15 minutes prior to imaging
    ●
        Uptake by healthy liver (Kupffer cells; RES)
    ●
        Cold in areas of disease
Dual Isotope Imaging
●
    1981: Moore et al
    ●
        Gastric emptying solid phase (Tc-99m sulfur
        colloid, 140 keV photopeak)
    ●
        Simultaneous liquid phase (In-111 DTPA 247
        keV photopeak)
Dual Energy Imaging
●
    1988: Raman Mistry
    ●
        “Dual Energy” imaging: initial acquisition of
        low energy radiopharmaceutical followed
        immediately by acquisition of high energy
        radiopharmaceutical (Manual of Nuclear
        Medicine Procedures, p154)
Cardiac DISA
●
    1990: Nakajima et al
    ●
        Tl-201: 1 mCi (perfusion)
    ●
        I-123 MIBG: 1 mCi (symathetic neuron
        activity)
    ●
        This study strictly looked at crosstalk
        –   One isotope injected
        –   Both energy windows imaged
Almost DISA
●
    1991: Crawley et al
    ●
        Crosstalk a problem (Nakajima et al)
●
    Conclusion
    ●
        Solution: image low energy first, followed
        immediately by high energy
    ●
        Improving techology has improved potential
        for accurate DISA (SPECT)
DISA: Ga67 & Tc99m
●
    1985: Karl et al
●
    Ga67-citrate & Tc99m
●
    Tc99m compounds used to localize Ga67
    activity
Subtraction: Ga67 & Tc99m
●
    1978: Dhawan et al
●
    Ga67 / Tc99m subtraction
●
    Conclusion
    ●
        Ga67 used to identify infection
    ●
        Tc99m MDP used to localize
    ●
        Technique worked
DISA: Lung
●
    1986: Klumper et al
●
    Tc99m microspheres for lung perfusion
●
    Kr81m gas (190 keV) for ventilation
●
    Conclusion
    ●
        Adequate energy separation obtained
    ●
        Simultaneous perfusion/ventilation images
        possible
Dual Tracer Single Acquisition
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
Myocardial Viability
DISA: SPECT vs PET
●
    2006: Slart, Bax et al
    ●
        DISA SPECT: Tc99m sestamibi + F18-FDG
    ●
        DISA PET: N13 ammonia + F18-FDG
●
    Endpoint: functional recovery
●
    Sensitivity: 90% vs 89% (NS)
●
    Specificity: 86% vs 86% (NS)
●
    CONCLUSION: SPECT = PET
DISA vs DIDA
●
    2002: Pagnanelli et al
    ●
        SPECT DISA: Tc99m sestamibi + F18-FDG
    ●
        SPECT DIDA: Tc99m sestamibi + F18-FDG
    ●
        DIDA = dual isotope dual acquisition
●
    Endpoint: concordance
●
    Conclusion: DISA = DIDA
    ●
        143 of 156 segments corcordant for viability
        vs non-viability
DISA vs Tl-201
●
    2005: Wu et al
●
    40 pts
●
    DISA: Tc99m sestamibi & FDG SPECT
●
    Tl-201 stress-reinjection SPECT
●
    Conclusion: DISA is superior
    ●
        16 pts underwent revascularization
    ●
        DISA predicted functional recovery (p<0.02)
        but Tl-201 did not (p=0.09)
DISA (mibi/FDG) = PET (N13, FDG)




 CONCLUSION: SPECT DISA works (2005, Matsunari et al)
DISA (mibi,FDG) = FDG PET




CONCLUSION: SPECT DISA works (2005, Slart, Bax et al)
Parathyroid
DTSA vs Single Tracer Washout
●
    2002: Leslie et al
●
    Tc99m pertech 1.5 mci followed by 30m
    dynamic imaging
●
    Tc99m sestamibi 35 mCi injected at 15m
●
    Delayed imaging at 2h
●
    Conclusion: DTSA Superior
    ●
        DTSA: 58/68 solitary adenomas
    ●
        Washout: 49/68 solitary adenomas
Myocardial Infaction
DISA: mibi & FDG in MI/viability




CONCLUSION: it works (2010 Huang – China - et al)
DISA: Tl-201 & In111 antimyosin




 CONCLUSION: it works (1992 Anthunes et al, Columbia U)
Myocardial Perfusion Imaging
DISA: Tl-201 / Tc-99m
●
    Initial study (1994) => too much cross-
    talk, DIDA technique recommended
●
    Subsequent studies with newer gamma
    cameras have found it now feasible
    ●
        2008: Steele et al (multi-pinhole camera)
    ●
        2010: Ben-Haim et al (D-Spect)
1994: DISA Tl / Tc Doesn't Work




        Too much crosstalk
2008: Now it does work




Why? Newer hardware and software
2010: Tl/Tc DISA works
Brain Imaging
DISA: Tc99m and I-123
brain dopamine pre- and postsynaptic neuron imaging




 CONCLUSION: imaging patients with movement disorders
 by using DISA 99mTc-TRODAT-1 and 123I-IBZM is feasible
 and potentially useful clinically. (2009, Kao et al, Taiwan)
DISA: Tc99m and I-123
brain dopamine pre- and postsynaptic neuron imaging




CONCLUSION: Energy separation of Tc99m from I-123 is
feasible; DISA using these agents has clinical potential (Du,
Frey 2009, JHU)
Dual Isotope Simultaneous
                 Acquisition
●
    Myocardial Viability
    ●
        Tc-99m sestamibi / 18F-FDG
    ●
        Simultaneous perfusion & metabolism
●
    Myocardial Perfusion
    ●
        Tc-99m sestamibi / Tl-201
    ●
        Simultaneous rest/stress
●
    Myocardial Fatty Acid Metabolism
    ●
        Tc-99m tetrofosmin / I-123 BMIPP
    ●
        Simultaneous perfusion/fatty acid metabolism
Dual Isotope Simultaneous
                Acquisition
●
    Brain
    ●
        Tc-99m TRODAT-1 / I-123 BZM
●
    Parathyroid
    ●
        Tc-99m pertechnetate / Tl-201 or Tc-99m
    ●
        Simultaneous thyroid / parathyroid
●
    Infection
    ●
        Tc-99m MDP / In-111 SPECT-CT / Ga67
    ●
        Tc-99m used for registration with CT
DISA PET
●
    2010,2011: Andreyev & Celler (UBC)
        st
●
    1 Tracer: pure positron emitter (F-18)
●
    2nd Tracer: includes high energy gamma
    ●
         Both Cu-60 and Na-22 used
●
    Approach
    ●
         Detect auxillary gamma in coincidence with
         annihilation event to identify 2nd tracer
●
    Conclusion: method works with relative
    errors of ~5% (Cu) to 7% (Na)
DISA
●
    CONCLUSIONS
    ●
        The technique is technically feasible
    ●
        Several different combinations work
    ●
        The technique has clinical value
    ●
        Applications are currently being developed
        for PET tracers as well
Dual Tracer Single Acquisition
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
NaF, FDG, or MDP?
●
    2011: Iagaru et al
●
    Sensitivity
    ●
        MDP: 22/52 pts
    ●
        NaF: 24/52 pts (identified all 22 MDP & 16 FDG)
    ●
        FDG: 16/52 pts (+ soft tissue lesions in 28 pts)
●
    Conclusion
    ●
        NaF identified all bony lesions
    ●
        FDG identified important additional lesions
    ●
        FDG/NaF combination “may be necessary”
DTSA PET/CT using FDG & NaF
●
    2009: Iagaru et al
●
    Prospective; 14 pts with proven cancer
    ●
        6 sarcoma, 3 prostate, 2 breast, 1 colon, 1
        lung, and 1 malignant paraganglioma
●
    Pts got 3 scans: NaF, FDG, and FDG/NaF
●
    DTSA vs FDG: no lesions missed
●
    DTSA vs NaF: 1 skull lesion missed, but
    this did not change clinical staging
Analysis
●
    DTSA vs FDG alone
    ●
        You won't miss any FDG+ lesions
●
    DTSA vs NaF alone
    ●
        May miss skull lesions
●
    DTSA vs NaF and FDG separately
    ●
        95% CI = 11 to 14 (worst case: 1 of 5 pts)
●
    Replacing FDG scans with DTSA
    ●
        1 DTSA = 1.8 FDG
Conclusion
   “The arguments mentioned here
advocate for the use of both 18F PET/CT
  and 18F-FDG PET/CT for the initial
   staging of patients with cancer. “
DTSA: NaF & FDG PET/CT
●
    2011: Iagaru (SNM abstract)
●
    78 pts
    ●
        DTSA provided good-quality imaging of both
        skeletal and extra-skeletal malignant lesions
    ●
        “The beauty of it (DTSA) is that each agent
        has its own strength, and those are unified in
        the imaging. In combination they represent
        a powerful new tool for acquiring as much
        information as possible about the extent of a
        patient’s cancer.” - A. Iagaru
DTSA: NaF & FDG PET/CT
●
    2011: Simoncic et al (abstract)
●
    3 pts with prostate cancer
    ●
        “The addition of FDG PET imaging to the
        osseous NaF PET imaging provides
        additional information to treatment
        response and has the potential to improve
        the assessment of bone metastasis in
        therapy.”
Combined NaF / FDG
   ●
       Case Report
   ●
       NaF => sclerotic bone lesions
   ●
       FDG => lytic bone lesions
       ●
           “Various types of bone metastases may
           coexist in a single patient”
       ●
           “the combination of both FDG and NaF
           PET/CT is likely to provide the most
           comprehensive assessment”
 Withofs N, Collignon J, Rorive A, Jerusalem G, Hustinx R. [Heterogeneity of bone metastases
in a patient with breast cancer: case report illustrating the potential of combining various
imaging techniques]. Rev Med Liege. 2011 May-Jun;66(5-6):288-90. French. PubMed PMID:
21826964.
SNM 2011
Dual Tracer Single Acquisition
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
Technique
●
    Work closely with radiopharmacist
●
    Get agreement from clinicians (we also
    got research committee approval)
●
    Customize FDG-to-NaF ratio as necessary
    ●
        Start with 3:1 (in separate syringes)
●
    Vertex => Toes
●
    90 minute uptake
●
    Calculate patient exposure levels
Technique
●
    Every camera is unique
    ●
        Doses can vary widely
    ●
        Imaging times may vary widely
    ●
        Cameras frequently require a settling in
        period before stabilizing
    ●
        Follow general guidelines, but customize to
        maximize your camera's capabilities
●
    Must have PET/CT hybrid imaging
Case 01: Breast Cancer
●
    49 y/o female
●
    Cc: suspicious lung and T12 lesions
●
    Technique
    ●
        DTSA PET/CT
    ●
        4:1 FDG-to-NaF (7.9 mCi to 2.1 mCi)
    ●
        90 minute uptake period
    ●
        Estimated total exposure: 17 mSv
    ●
        16-slice Siemens PET/CT (2010)
Case 01
●
    Clinical concern was for both soft tissue
    and bone lesions
●
    DTSA in a single study evaluated both
    with high accuracy
●
    No additional imaging necessary at this
    time
Case 02: Breast Cancer
●
    64 y/o female
●
    Initial workup of bilateral invasive ductal
    carcinoma
●
    Technique
    ●
        DTSA PET/CT
    ●
        3:1 FDG-to-NaF (6.4 mCi to 2.1 mCi)
    ●
        90 minute uptake period
    ●
        Estimated total exposure: 19 mSv
Case 02: Tips
●
    Bone uptake must be correlated with CT
●
    It is easy to over-call lesions when starting
    out with NaF
    ●
        CT correlation greatly reduces false-positives
●
    Must look at multiple views & contrasts
    ●
        3D
    ●
        Axial
    ●
        Coronal
    ●
        Sagittal
Case 02: Conclusion
●
    Bone lesions appear most likely
    degenerative
●
    No additional soft tissue lesions outside
    of the breasts
●
    Would an additional bone scan help?
    ●
        No, because false-positives > true positives
●
    Would a dedicated NaF PET/CT help?
    ●
        Would double costs & patient exposure
    ●
        MRI or other imaging probably better
Case 03: Breast Cancer
●
    61 y/o female
●
    Restaging breast cancer, recent chemo
●
    Technique
    ●
        DTSA PET/CT
    ●
        3:1 FDG-to-NaF (7.05 mCi to 2.35 mCi)
    ●
        90 minute uptake period
    ●
        Estimated total exposure: 15 mSv
Case 03: Conclusion
●
    DTSA similar in appearance to recent
    GCSF
●
    DTSA clinical value in this patient
    population unknown but likely
    decreased
Dual Tracer Single Acquisition
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
“Indeed, we try to improve the
   patient's condition as soon as
  possible. It is clearly unethical to
delay treatment in order to compare
   two diagnostic techniques, so
simultaneous imaging would be the
ideal method but for the problem of
              crossover.”
                 J. Crawley & T. Smith, 1991
“The use of a single examination
opens the possibility for improved
         patient care.”
                  SS Gambhir et al, 2009
“I'm Third”
●
    Patient first
●
    Greater society second
●
    I'm third
Clinical Care
●
    CON
    ●
        Possibility of missed skull lesions due to
        proximity of high FDG uptake by brain
    ●
        Possibility of making a good scan (FDG) not
        as good due to lower dosages (DTSA)
    ●
        …. but dosages generally significantly lower
        in Europe, and there does not appear to be a
        decrease in FDG PET/CT sensitivity or
        specificity
Clinical Care
●
    PRO
    ●
        Greater sensitivity (probably)
    ●
        Patients more likely to get both FDG and NaF
        scans actually done (definitely)
    ●
        Separate scans increase no-show rate
    ●
        Separate scans more likely to be denied by
        insurances
    ●
        Maximizes clinical yield (1 = 1.8)
Socioeconomics
●
    CON
    ●
        Added cost of making NaF/FDG cocktail may
        drive up imaging costs
    ●
        If DTSA is inferior (unlikely), then
        misdiagnosis rate would drive up costs
Socioeconomics
●
    PRO
    ●
        Misdiagnosis rate likely to be decreased,
        which will decrease costs
    ●
        DTSA likely to decrease total # of scans
    ●
        DTSA saves patient time & energy
    ●
        Getting the greatest amount of information
        from a single scan is essential in a limited
        resources environment
Limitations
●
    Primary
    ●
        Difficult to get radiopharmacies to create
        compound
●
    Secondary
    ●
        Lack of research
Dual Tracer Single Acquisition
●
    Historical background
●
    DTSA: different radioisotopes
●
    DTSA: different radiopharmaceuticals
●
    DTSA: case studies
●
    DTSA: pros and con
●
    Conclusions
Evidence-Based Medicine
●
    The available evidence indicates
    superiority of DTSA over FDG alone
    ●
        Clinically
    ●
        Socioeconomically
●
    There is no evidence showing DTSA to be
    inferior to separate FDG and NaF scans
    ●
        DTSA = FDG
    ●
        DTSA = NaF (clinically)
Conclusions
●
    NaF/FDG DTSA vs FDG alone will improve
    clinical care
    ●
        1 DTSA = 1.8 FDG
    ●
        More likely than not: improved initial staging
    ●
        More likely than not: will reduce costs
    ●
        Uncertain: role in follow-up imaging
●
    More clinical experience is needed
●
    More research is needed
Contact Information
Thank You!
Thomas F. Heston, MD




            Photo by Rick Leche - used with permission

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Dual Tracer Single Acquisition Imaging in Nuclear Medicine

  • 1. Dual Tracer Single Acquisition Imaging Thomas F Heston, MD Medical Director of Nuclear Medicine, Family Care Network, Bellingham, Washington. Assistant Professor of Radiology (Adjunct), Johns Hopkins Hospital, Baltimore, Maryland. Presented at the Missouri Valley Chapter of the Society of Nuclear Medicine 33rd Annual Meeting, 2011, Lake of the Ozarks, Missouri
  • 3. Learning Objectives ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pro and con ● Conclusions
  • 4. Dual Tracer Single Acquisition ● Historical background: pre-2000 ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 5. DISA: Gastric Emptying ● 1974: RC Heading ● Cornflakes and milk meal ● Liquid Phase: 200 uCi In-113m DTPA ● Solid Phase: ~ 30 pieces of filter paper, 3mm square, impregnated with 200 uCi Tc-99m sulphur colloid, coated with a thin film of perspex (poly methyl methacrylate) ● Conclusion: solid & liquid components of emptying differ, and may be relevent clinically after gastric surgery
  • 6.
  • 7. DISA: Liver Scans ● 1976: Buraggi et al ● Ga-67 ● 3 mCi 48 hours prior to imaging ● Concentrates in areas of inflammation and rapid cell division ● Tc-99m sulfur colloid ● 1 mCi 15 minutes prior to imaging ● Uptake by healthy liver (Kupffer cells; RES) ● Cold in areas of disease
  • 8.
  • 9. Dual Isotope Imaging ● 1981: Moore et al ● Gastric emptying solid phase (Tc-99m sulfur colloid, 140 keV photopeak) ● Simultaneous liquid phase (In-111 DTPA 247 keV photopeak)
  • 10.
  • 11. Dual Energy Imaging ● 1988: Raman Mistry ● “Dual Energy” imaging: initial acquisition of low energy radiopharmaceutical followed immediately by acquisition of high energy radiopharmaceutical (Manual of Nuclear Medicine Procedures, p154)
  • 12. Cardiac DISA ● 1990: Nakajima et al ● Tl-201: 1 mCi (perfusion) ● I-123 MIBG: 1 mCi (symathetic neuron activity) ● This study strictly looked at crosstalk – One isotope injected – Both energy windows imaged
  • 13.
  • 14. Almost DISA ● 1991: Crawley et al ● Crosstalk a problem (Nakajima et al) ● Conclusion ● Solution: image low energy first, followed immediately by high energy ● Improving techology has improved potential for accurate DISA (SPECT)
  • 15.
  • 16. DISA: Ga67 & Tc99m ● 1985: Karl et al ● Ga67-citrate & Tc99m ● Tc99m compounds used to localize Ga67 activity
  • 17.
  • 18. Subtraction: Ga67 & Tc99m ● 1978: Dhawan et al ● Ga67 / Tc99m subtraction ● Conclusion ● Ga67 used to identify infection ● Tc99m MDP used to localize ● Technique worked
  • 19.
  • 20. DISA: Lung ● 1986: Klumper et al ● Tc99m microspheres for lung perfusion ● Kr81m gas (190 keV) for ventilation ● Conclusion ● Adequate energy separation obtained ● Simultaneous perfusion/ventilation images possible
  • 21.
  • 22. Dual Tracer Single Acquisition ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 24. DISA: SPECT vs PET ● 2006: Slart, Bax et al ● DISA SPECT: Tc99m sestamibi + F18-FDG ● DISA PET: N13 ammonia + F18-FDG ● Endpoint: functional recovery ● Sensitivity: 90% vs 89% (NS) ● Specificity: 86% vs 86% (NS) ● CONCLUSION: SPECT = PET
  • 25.
  • 26. DISA vs DIDA ● 2002: Pagnanelli et al ● SPECT DISA: Tc99m sestamibi + F18-FDG ● SPECT DIDA: Tc99m sestamibi + F18-FDG ● DIDA = dual isotope dual acquisition ● Endpoint: concordance ● Conclusion: DISA = DIDA ● 143 of 156 segments corcordant for viability vs non-viability
  • 27.
  • 28. DISA vs Tl-201 ● 2005: Wu et al ● 40 pts ● DISA: Tc99m sestamibi & FDG SPECT ● Tl-201 stress-reinjection SPECT ● Conclusion: DISA is superior ● 16 pts underwent revascularization ● DISA predicted functional recovery (p<0.02) but Tl-201 did not (p=0.09)
  • 29.
  • 30. DISA (mibi/FDG) = PET (N13, FDG) CONCLUSION: SPECT DISA works (2005, Matsunari et al)
  • 31. DISA (mibi,FDG) = FDG PET CONCLUSION: SPECT DISA works (2005, Slart, Bax et al)
  • 33. DTSA vs Single Tracer Washout ● 2002: Leslie et al ● Tc99m pertech 1.5 mci followed by 30m dynamic imaging ● Tc99m sestamibi 35 mCi injected at 15m ● Delayed imaging at 2h ● Conclusion: DTSA Superior ● DTSA: 58/68 solitary adenomas ● Washout: 49/68 solitary adenomas
  • 34.
  • 36. DISA: mibi & FDG in MI/viability CONCLUSION: it works (2010 Huang – China - et al)
  • 37. DISA: Tl-201 & In111 antimyosin CONCLUSION: it works (1992 Anthunes et al, Columbia U)
  • 39. DISA: Tl-201 / Tc-99m ● Initial study (1994) => too much cross- talk, DIDA technique recommended ● Subsequent studies with newer gamma cameras have found it now feasible ● 2008: Steele et al (multi-pinhole camera) ● 2010: Ben-Haim et al (D-Spect)
  • 40. 1994: DISA Tl / Tc Doesn't Work Too much crosstalk
  • 41. 2008: Now it does work Why? Newer hardware and software
  • 44. DISA: Tc99m and I-123 brain dopamine pre- and postsynaptic neuron imaging CONCLUSION: imaging patients with movement disorders by using DISA 99mTc-TRODAT-1 and 123I-IBZM is feasible and potentially useful clinically. (2009, Kao et al, Taiwan)
  • 45. DISA: Tc99m and I-123 brain dopamine pre- and postsynaptic neuron imaging CONCLUSION: Energy separation of Tc99m from I-123 is feasible; DISA using these agents has clinical potential (Du, Frey 2009, JHU)
  • 46. Dual Isotope Simultaneous Acquisition ● Myocardial Viability ● Tc-99m sestamibi / 18F-FDG ● Simultaneous perfusion & metabolism ● Myocardial Perfusion ● Tc-99m sestamibi / Tl-201 ● Simultaneous rest/stress ● Myocardial Fatty Acid Metabolism ● Tc-99m tetrofosmin / I-123 BMIPP ● Simultaneous perfusion/fatty acid metabolism
  • 47. Dual Isotope Simultaneous Acquisition ● Brain ● Tc-99m TRODAT-1 / I-123 BZM ● Parathyroid ● Tc-99m pertechnetate / Tl-201 or Tc-99m ● Simultaneous thyroid / parathyroid ● Infection ● Tc-99m MDP / In-111 SPECT-CT / Ga67 ● Tc-99m used for registration with CT
  • 48. DISA PET ● 2010,2011: Andreyev & Celler (UBC) st ● 1 Tracer: pure positron emitter (F-18) ● 2nd Tracer: includes high energy gamma ● Both Cu-60 and Na-22 used ● Approach ● Detect auxillary gamma in coincidence with annihilation event to identify 2nd tracer ● Conclusion: method works with relative errors of ~5% (Cu) to 7% (Na)
  • 49.
  • 50.
  • 51. DISA ● CONCLUSIONS ● The technique is technically feasible ● Several different combinations work ● The technique has clinical value ● Applications are currently being developed for PET tracers as well
  • 52. Dual Tracer Single Acquisition ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 53. NaF, FDG, or MDP? ● 2011: Iagaru et al ● Sensitivity ● MDP: 22/52 pts ● NaF: 24/52 pts (identified all 22 MDP & 16 FDG) ● FDG: 16/52 pts (+ soft tissue lesions in 28 pts) ● Conclusion ● NaF identified all bony lesions ● FDG identified important additional lesions ● FDG/NaF combination “may be necessary”
  • 54.
  • 55. DTSA PET/CT using FDG & NaF ● 2009: Iagaru et al ● Prospective; 14 pts with proven cancer ● 6 sarcoma, 3 prostate, 2 breast, 1 colon, 1 lung, and 1 malignant paraganglioma ● Pts got 3 scans: NaF, FDG, and FDG/NaF ● DTSA vs FDG: no lesions missed ● DTSA vs NaF: 1 skull lesion missed, but this did not change clinical staging
  • 56.
  • 57. Analysis ● DTSA vs FDG alone ● You won't miss any FDG+ lesions ● DTSA vs NaF alone ● May miss skull lesions ● DTSA vs NaF and FDG separately ● 95% CI = 11 to 14 (worst case: 1 of 5 pts) ● Replacing FDG scans with DTSA ● 1 DTSA = 1.8 FDG
  • 58. Conclusion “The arguments mentioned here advocate for the use of both 18F PET/CT and 18F-FDG PET/CT for the initial staging of patients with cancer. “
  • 59. DTSA: NaF & FDG PET/CT ● 2011: Iagaru (SNM abstract) ● 78 pts ● DTSA provided good-quality imaging of both skeletal and extra-skeletal malignant lesions ● “The beauty of it (DTSA) is that each agent has its own strength, and those are unified in the imaging. In combination they represent a powerful new tool for acquiring as much information as possible about the extent of a patient’s cancer.” - A. Iagaru
  • 60. DTSA: NaF & FDG PET/CT ● 2011: Simoncic et al (abstract) ● 3 pts with prostate cancer ● “The addition of FDG PET imaging to the osseous NaF PET imaging provides additional information to treatment response and has the potential to improve the assessment of bone metastasis in therapy.”
  • 61.
  • 62. Combined NaF / FDG ● Case Report ● NaF => sclerotic bone lesions ● FDG => lytic bone lesions ● “Various types of bone metastases may coexist in a single patient” ● “the combination of both FDG and NaF PET/CT is likely to provide the most comprehensive assessment” Withofs N, Collignon J, Rorive A, Jerusalem G, Hustinx R. [Heterogeneity of bone metastases in a patient with breast cancer: case report illustrating the potential of combining various imaging techniques]. Rev Med Liege. 2011 May-Jun;66(5-6):288-90. French. PubMed PMID: 21826964.
  • 63.
  • 64.
  • 66.
  • 67. Dual Tracer Single Acquisition ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 68. Technique ● Work closely with radiopharmacist ● Get agreement from clinicians (we also got research committee approval) ● Customize FDG-to-NaF ratio as necessary ● Start with 3:1 (in separate syringes) ● Vertex => Toes ● 90 minute uptake ● Calculate patient exposure levels
  • 69. Technique ● Every camera is unique ● Doses can vary widely ● Imaging times may vary widely ● Cameras frequently require a settling in period before stabilizing ● Follow general guidelines, but customize to maximize your camera's capabilities ● Must have PET/CT hybrid imaging
  • 70. Case 01: Breast Cancer ● 49 y/o female ● Cc: suspicious lung and T12 lesions ● Technique ● DTSA PET/CT ● 4:1 FDG-to-NaF (7.9 mCi to 2.1 mCi) ● 90 minute uptake period ● Estimated total exposure: 17 mSv ● 16-slice Siemens PET/CT (2010)
  • 71.
  • 72.
  • 73. Case 01 ● Clinical concern was for both soft tissue and bone lesions ● DTSA in a single study evaluated both with high accuracy ● No additional imaging necessary at this time
  • 74. Case 02: Breast Cancer ● 64 y/o female ● Initial workup of bilateral invasive ductal carcinoma ● Technique ● DTSA PET/CT ● 3:1 FDG-to-NaF (6.4 mCi to 2.1 mCi) ● 90 minute uptake period ● Estimated total exposure: 19 mSv
  • 75.
  • 76.
  • 77. Case 02: Tips ● Bone uptake must be correlated with CT ● It is easy to over-call lesions when starting out with NaF ● CT correlation greatly reduces false-positives ● Must look at multiple views & contrasts ● 3D ● Axial ● Coronal ● Sagittal
  • 78. Case 02: Conclusion ● Bone lesions appear most likely degenerative ● No additional soft tissue lesions outside of the breasts ● Would an additional bone scan help? ● No, because false-positives > true positives ● Would a dedicated NaF PET/CT help? ● Would double costs & patient exposure ● MRI or other imaging probably better
  • 79. Case 03: Breast Cancer ● 61 y/o female ● Restaging breast cancer, recent chemo ● Technique ● DTSA PET/CT ● 3:1 FDG-to-NaF (7.05 mCi to 2.35 mCi) ● 90 minute uptake period ● Estimated total exposure: 15 mSv
  • 80.
  • 81. Case 03: Conclusion ● DTSA similar in appearance to recent GCSF ● DTSA clinical value in this patient population unknown but likely decreased
  • 82. Dual Tracer Single Acquisition ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 83. “Indeed, we try to improve the patient's condition as soon as possible. It is clearly unethical to delay treatment in order to compare two diagnostic techniques, so simultaneous imaging would be the ideal method but for the problem of crossover.” J. Crawley & T. Smith, 1991
  • 84. “The use of a single examination opens the possibility for improved patient care.” SS Gambhir et al, 2009
  • 85. “I'm Third” ● Patient first ● Greater society second ● I'm third
  • 86. Clinical Care ● CON ● Possibility of missed skull lesions due to proximity of high FDG uptake by brain ● Possibility of making a good scan (FDG) not as good due to lower dosages (DTSA) ● …. but dosages generally significantly lower in Europe, and there does not appear to be a decrease in FDG PET/CT sensitivity or specificity
  • 87. Clinical Care ● PRO ● Greater sensitivity (probably) ● Patients more likely to get both FDG and NaF scans actually done (definitely) ● Separate scans increase no-show rate ● Separate scans more likely to be denied by insurances ● Maximizes clinical yield (1 = 1.8)
  • 88. Socioeconomics ● CON ● Added cost of making NaF/FDG cocktail may drive up imaging costs ● If DTSA is inferior (unlikely), then misdiagnosis rate would drive up costs
  • 89. Socioeconomics ● PRO ● Misdiagnosis rate likely to be decreased, which will decrease costs ● DTSA likely to decrease total # of scans ● DTSA saves patient time & energy ● Getting the greatest amount of information from a single scan is essential in a limited resources environment
  • 90. Limitations ● Primary ● Difficult to get radiopharmacies to create compound ● Secondary ● Lack of research
  • 91. Dual Tracer Single Acquisition ● Historical background ● DTSA: different radioisotopes ● DTSA: different radiopharmaceuticals ● DTSA: case studies ● DTSA: pros and con ● Conclusions
  • 92. Evidence-Based Medicine ● The available evidence indicates superiority of DTSA over FDG alone ● Clinically ● Socioeconomically ● There is no evidence showing DTSA to be inferior to separate FDG and NaF scans ● DTSA = FDG ● DTSA = NaF (clinically)
  • 93. Conclusions ● NaF/FDG DTSA vs FDG alone will improve clinical care ● 1 DTSA = 1.8 FDG ● More likely than not: improved initial staging ● More likely than not: will reduce costs ● Uncertain: role in follow-up imaging ● More clinical experience is needed ● More research is needed
  • 95. Thank You! Thomas F. Heston, MD Photo by Rick Leche - used with permission