PET
Guillermo Gilligan
Jornadas Nacionales de Radiologia Pediatrica 2014
Sociedad Argentina de Pediatria
9 de agosto 2014
Respuestas de la Imagen Molecular Indicadores precoces de efectividad terapeutica
que pueden mejorar la atencion
••Reduciendo uso de medicacion Reduciendo uso de medicacion
inefectivainefectiva
Imagenes Convencionales = Reduccion tamaño Tumoral, o Imagenes Convencionales = Reduccion tamaño Tumoral, o
desaparicion , o cambio cualitativoTumoraldesaparicion , o cambio cualitativoTumoral
inefectivainefectiva
••Reduciendo procedimientos que no Reduciendo procedimientos que no
ayudan ayudan
••Reduciendo costosReduciendo costos
••Mejorando calidad de vida y sobrevidaMejorando calidad de vida y sobrevida
PILAR DE LAPILAR DE LA
SENSIBILIDAD=SENSIBILIDAD=
Capacidad deCapacidad de
concentracionconcentracion
MAPA DE LA DISTRIBUCION
CORPORAL DE LA HEXOQUINASA
TUBERCULOSIS
SARCOIDOSIS
ENFERMEDADES GRANULOMATOSAS
MICOSIS SISTEMICAS PROFUNDAS
OSTEOMIELITIS(especialmente con
Injuria estructural osea o hueso violado)Injuria estructural osea o hueso violado)
IMAGEN FUNCIONAL CON PET en Sarcomas
Aplicaciones
• Benigno versus maligno
• Gradacion
• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia
• Estadificacion
•Monitoreo terapeutico
• Reestadificacion ( recurrencia local )
June 2012, Volume 198, Number 6
Nuclear Medicine and Molecular Imaging
Original Research
Correlating Metabolic Activity on 18F-FDG PET/CT With Histopathologic Characteristics of Osseous and
Soft-Tissue Sarcomas: A Retrospective Review of 136 Patients
Rajan Rakheja1, William Makis2, Sonia Skamene1, Ayoub Nahal3, Fadi Brimo3, Laurent Azoulay4 5,
Jonathan Assayag6, Robert Turcotte5 and Marc Hickeson1
OBJECTIVE. The objective of our study was to determine whether there is a statistically significant correlation between
metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value
(SUVmax) on 18F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis,
and the presence of a myxoid component
MATERIALS AND METHODS. We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous
sarcoma who underwent 18F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUVmax of each
primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the
final pathology reports
RESULTS. Histopathologic data were available for 136 sarcomas. The median SUVmax values of sarcomas with mitotic
counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00–6.99, 7.00–16.24, and 16.25 or greater were 5.0, 6.6, 10.3, counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00–6.99, 7.00–16.24, and 16.25 or greater were 5.0, 6.6, 10.3,
and 13.0, respectively (p = 0.0003). The median SUVmax for the sarcomas with necrosis (90 patients) was 8.6 and for
those without necrosis (43 patients), 6.0 (p = 0.026). The median SUVmax for the sarcomas without a myxoid component
(118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28).
CONCLUSION. There was a statistically significant correlation between the mitotic count significant correlation between the mitotic count
and the SUVmax as well as between the presence of tumor necrosis and the SUVmax.and the SUVmax as well as between the presence of tumor necrosis and the SUVmax.
Although a correlation between the presence of a myxoid component and SUVmax was
shown, it was not found to be statistically significant. These findings improve on the current These findings improve on the current
information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy.information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy.
Correlating the SUVmax with histologic markers that also feature prominently in major
sarcoma grading systems may help improve the accuracy of grading and of prognostication may help improve the accuracy of grading and of prognostication
by allowing the SUVmax to potentially serve by allowing the SUVmax to potentially serve as a surrogate markeras a surrogate marker in these grading in these grading
systems, particularly in cases in which there is interobserver disagreement in the pathologic systems, particularly in cases in which there is interobserver disagreement in the pathologic
diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of
histopathologic evaluation alone.histopathologic evaluation alone.
Grado vs SUV (por percentilo)
n = 89
25% 50% 75%
BEN 1.5 3.8 6.9
PET en Sarcoma
Aplicaciones – Gradacion tumoral
Folpe AL et al. Clin Cancer Res 2000; 6: 1279-1287
BEN 1.5 3.8 6.9
G1 1.55 2.65 4.11
G2 3.40 6.05 10.25
G3 4.22 6.85 19.35
IMAGEN FUNCIONAL CON PET en Sarcoma
Aplicaciones
• Benigno versus maligno
• Gradacion
• Guia para obtener la mejor muestra biopsia(HETEROGENEIDAD)• Guia para obtener la mejor muestra biopsia(HETEROGENEIDAD)
• Estadificacion
•monitoreo terapeutico
• Reestadificacion ( recurrencia local)
• Gran masa en muslo
izquierdo e imagenes de
RMN consistentes con
liposarcoma
• Biopsia guiada hacia la Biopsia guiada hacia la
PET en Sarcoma
Aplicaciones – Guiando biopsia
• Biopsia guiada hacia la Biopsia guiada hacia la
region metabolicamente region metabolicamente
mas elevada confirmo mas elevada confirmo
tumor de alto grado de tumor de alto grado de
malignidadmalignidad
• Multiples metastasis
subcutaneas tambien
detectadas por el PET
IMAGEN FUNCIONAL CON PET en Sarcoma
Aplicaciones
• Benigno versus maligno
• Gradacion
• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia
• Estadificacion
•Monitoreo terapeutico
• Reestadificacion ( recurrencia local)
July 2001, Volume 177, Number 1
Pediatric Imaging
Whole-Body MR Imaging for Detection of Bone Metastases in Children and Young Adults
Comparison with Skeletal Scintigraphy and FDG PETHeike E. Daldrup-Link1 2, Christiane Franzius3, Thomas M. Link1 2, Daniela Laukamp1, Joachim Sciuk3,
Heribert Jürgens4, Otmar Schober3 and Ernst J. Rummeny1
OBJECTIVE. The purpose of this study was to compare the diagnostic accuracy of whole-body MR
imaging, skeletal scintigraphy, and 18F-fluorodeoxyglucose (FDG) positron emission tomography
(PET) for the detection of bone metastases in children.
SUBJECTS AND METHODS. Thirty-nine children and young adults who were 2-19 years old and who had Ewing's sarcoma, osteosarcoma, lymphoma, rhabdomyosarcoma, melanoma, and Langerhans' cell
histiocytosis underwent whole-body spin-echo MR imaging, skeletal scintigraphy, and FDG PET for the initial
staging of bone marrow metastases. The number and location of bone and bone marrow lesions diagnosed with
each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference. each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference.
RESULTS. Twenty-one patients exhibited 51 bone metastases. Sensitivities for the detection of bone metastases were 90%
for FDG PET, 82% for whole-body MR imaging, and 71% for skeletal scintigraphy; these data were significantly different (p
< 0.05). False-negative lesions were different for the three imaging modalities, mainly depending on lesion location. Most
false-positive lesions were diagnosed using FDG PET.
CONCLUSION.
Whole-body MR imaging has a higher sensitivity than skeletal
scintigraphy for the detection of bone marrow metastases but
a lower sensitivity than FDG PET
PET en SarcomasAplicaciones - Estadificacion
• TAC superior al FDG PET para detectar MTTS pulmonares (1,2)
• PET puede identificar masas falsamente positivas de TAC
• VPN proporcional a la menor captacion en el tumor primario
• FDG PET tiene mayor sensibilidad que la TAC para metastasis de
1. Franzius C et al Ann Oncol 2001; 12:479-486
2. Lucas JD et al J Bone Joint Surg Br 1998; 80:441-447
3. Franzius C et al Eur J Nucl Med 2000; 27:1305-1311
tejidos blandos (2)
• FDG PET de cuerpo entero superior al centellograma oseo para
metastasis oseas (3)
• FDG-PET NO se discapacita por susceptibilidad al metal o
artefactos generados por metales
• Estudios multiples indican buena seguridad del FDG PET para la
deteccion de recurrencia tardia local
PET en SarcomasAplicaciones– Sospecha de
recurrencia local
Franzius C et al Ann Oncol 2002;13:157-160
Garcia R et al J Nucl Med 1996; 37:1476-1479
el Zeftawy H et al Cancer Biother Radiopharm 2001; 16:37-46
Bredella M et al AJR 2002; 179:1145-1150
Johnson GR et al Clin Nucl Med 2003; 28:815-820
deteccion de recurrencia tardia local
IMAGEN FUNCIONAL CON PET en Sarcomas
Aplicaciones
• Benigno versus maligno
• Gradacion
• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia
• Estadificacion
•Monitoreo terapeutico
• Reestadificacion ( recurrencia local )
Respuesta Tumoral
1. Crecimiento enlentecido
2. Estasis
3. Necrosis ( coagulativa, licuefactiva)
4. Hemorragia
5. Seria acumulacion de fluidos5. Seria acumulacion de fluidos
6. Formacion de Tejido de Granulacion
7. Formacion de cicatriz
8. Perdida de vascularizacion
9. Perdida de elementos malignos
Definiendo Respuesta TumoralInterrogantes clinicos
1. Cuan temprano puedo detectar respuesta?
2. Cual es el mejor agente de tratamiento?
3. Es una imagen de la respuesta sustituto, o equivalente
de la efectividad del tratamiento?
4. PUEDE inferirse la evolucion del paciente?
5. Predice la imagen de la respuesta el curso posterior
del paciente , su evolucion?
Redefiniendo Respuesta Tumoral
Parametros Biologicos Tumorales Cuantificables por PETParametros Biologicos Tumorales Cuantificables por PET
• Osteosarcoma femoral
izquierdo tratado con
PET en SarcomasAplicaciones – monitoreo terapeutico
Basal Post-QTP
MIP
izquierdo tratado con
quimioterapia adyuvante
• Respuesta metabolica Respuesta metabolica
completacompleta
PET Transaxial
PET-CT
SUV = 7,8 SUV = 0,6
PRE QTPPRE QTP
SUV 7,4SUV 7,4
(corte hasta(corte hasta(corte hasta(corte hasta
2,5)2,5)
POST QTPPOST QTP
2 DOSIS2 DOSIS
SUV 0.9SUV 0.9
April 2005, Volume 184, Number 4 - Pediatric Imaging
Pictorial Essay
PET/CT in the Evaluation of Childhood Sarcomas
M. Beth McCarville1 2, Ryan Christie2, Najat C. Daw3, Sheri L. Spunt3 and Sue C. Kaste
CONCLUSION. We found PET/CT useful in depicting an unknown primary
rhabdomyosarcoma and detecting unsuspected and unusual metastatic sites of childhood
sarcomas. It was useful in monitoring response to chemotherapy, radiation therapy, and
radiofrequency ablation and aided the postoperative evaluation of tumor resection sites
Fig. 6A. —16-year-
old boy with large
right pelvic Ewing's
Fig. 6B. —16-year-old boy
with large right pelvic right pelvic Ewing's
sarcoma, treated
preoperatively with
chemotherapy and
radiation therapy.
Maximum-intensity-
projection PET
image, obtained
before neoadjuvant
therapy, shows
intense FDG activity
in primary tumor
(arrow) without
evidence of
metastatic disease.
with large right pelvic
Ewing's sarcoma, treated
preoperatively with
chemotherapy and radiation
therapy. Maximum-intensity-
projection PET image,
obtained after neoadjuvant
therapy, shows minimal
activity within tumor (arrow),
suggestive of good
response. Pathologic Pathologic
inspection of resected inspection of resected
tumor showed less than tumor showed less than
5% residual viable tumor.5% residual viable tumor.
(a)
Figure 4: FDG-
PET/CT at
baseline, early
followup, and
after completion
of neoadjuvant
treatments in a
(b)
histopathological
responder (a)
and a
nonresponder
(b).
(a)
Figure 4: FDG-
PET/CT at
baseline, early
followup, and
after completion
of neoadjuvant
treatments in a
(b)
histopathological
responder (a)
and a
nonresponder
(b).
(a) ∆SUV Baseline-Followup (bars) and
SUVmax at Followup (numerical)
(b) ∆Size Baseline-Followup
Figure 3: (a) SUVmax values (numerical) and changes in SUVmax (bars) after completion of
neoadjuvant treatment for each patient. (b) depicts changes in tumor size from baseline to
end of treatment. Histopathologic responders are illustrated in orange. Three of four
histopathologic responders showed decreases in SUVmax by ≥60% from baseline to
followup scan. One histopathologic responder with a 38% decrease in FDG uptake from
baseline to followup showed an SUVmax value after completion of neoadjuvant therapy of
<2.5 and was therefore correctly classified. Size changes in response to treatment were
marginal.
IMAGEN FUNCIONAL CON PET en Sarcoma
Aplicaciones - Conclusiones
• Estadificacion y reestadificacion(Barrido de cuerpo entero util )
Auxilio valioso en evaluar posibles recurrencias locales
•Monitoreo terapeutico
ENORME valor clinico ENORME valor clinico
Cambios rapidamente evidenciables ( semanas)
Se requieren mas estudios para mejorar y estratificar la cuantificacion de la respuesta
Potenciales ventajas con trazadores alternativos ( FLT hipoxia, sintesis proteica, intervencion genetica, etc.)
IMAGEN FUNCIONAL CON PET en Sarcomas
Aplicaciones - Conclusiones
• Posible marcador grado benignidad vs . malignidad
provee informacion complementaria util
Debe considerarse en el contexto clinico (cuando!!)
Pareceria poder asumir valor pronostico independiente, Pareceria poder asumir valor pronostico independiente, necesitando mas estudios al respecto
• Utilidad conductora al seleccionar sitio a biopsiar
MUY valioso, particularmente PET/CT – extendido a intevenciones quirurgicas y/o radioterapeuticas
PET : Componentes
• Scanner – detector que exploraexplorael paciente y efectua reconstruccion tomograficareconstruccion tomografica
• Ciclotron - produce el emisor el emisor de positrones a detectarde positrones a detectarde positrones a detectarde positrones a detectarModulo de sintesis- produce el elemento ,compuesto o elemento ,compuesto o MOLECULA MOLECULA que se UNIRA por reaccion quimica al emisor de positrones y se incorporara al incorporara al proceso metabolico a explorarproceso metabolico a explorar
CPET
State of the Art Clinical Positron Emission Tomograph
Advanced detector technologyAdvanced detector technology
�� improved resolutionimproved resolution
Design features & benefitsDesign features & benefits
AMPLIA PROYECCION ASISTENCIAL DE UNA HERRAMIENTA DE INVESTIGACION
DIRECTA, CON EXPLORACIONES FUNCIONALES UNICAS Y NOTABLES
MEJORAS EN LA RESOLUCION ,CAPAZ DE CUANTIFICAR REALES MEDIDAS DE
CONCENTRACION DE LOS TRAZADORES CON UN FUTURO LIBRE DEL
CICLOTRON,PIONERO EN FUSION CON OTRAS TECNICAS TOMOGRAFICAS
A D A CADAC Laboratories
ADAC-PET Vers. 5.2 18
�� improved resolutionimproved resolution
(5 mm @ center)(5 mm @ center)
�� betterbetter homogeinityhomogeinity
�� larger diameterlarger diameter
(92 cm)(92 cm)
� Better image quality
fusión de imágenes(con TAC)Mapeo funcional Mapeo anatomico
Semicuantificacion Semicuantificacion
EXTREMA
SENSIBILIDAD
Proporcionamente
En algunas
situaciones
MENOR
ESPECIFICIDAD
Comienza a depender
Del operador
MENOR SENSIBILIDAD RELATIVA
•Anatomía
+ Función
•Eleva la especificidad
•Mejora localización especialmente en algunos
sitios como abdomen,pelvis o cuello
•Reduce en casos los resultados falsos +
•En otros es de poco valor , superflua.
Semicuantificacion
metabolica
Semicuantificacion
densitometrica
FUSION de PET + TAC = “ PIEDRA ROSETA “ para la “civilizacion anatomista “
Del operador
Mejora sobre todo ESPECIFICIDAD ,sin abandonar rol estadificador , mejorando la
comprension de localizacion de los hallazgos del PET , auxiliando especialmente algunas
Tacticas medicas desarrolladas sobre bases ANATOMICAS (Ej: Cirugia – Radioterapia)
YA VIMOS LA MESA , LOS PLATOS , LOS
CUBIERTOS Y LA ETIQUETA A CUMPLIR
( TODOS VALIOSOS , COMPLEJOS Y
ELEGANTES ) PERO /..ELEGANTES ) PERO /..
¿¿¿ QUE HAY DE COMER $????¿¿¿ QUE HAY DE COMER $????
(EL MENU POSITRONICO)
SEGURIDAD RADIOLOGICA
JUSTIFICACION DE
LA PRACTICA
LIMITACION
DE LA
DOSIS
OPTIMIZACION DE LA
PROTECCION
POR QUE <.????
(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from
a single whole-body 18F-FDG PET/CT examination at a given age.
Huang B et al. Radiology 2009;251:166-174
©2009 by Radiological Society of North America
(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from a single whole-body 18F-FDG PET/CT examination at a given age.
(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from a single whole-body 18F-FDG PET/CT examination at a given age.
Huang B et al. Radiology 2009;251:166-174
©2009 by Radiological Society of North America
Huang B et al. Radiology 2009;251:166-174
©2009 by Radiological Society of North America
PET : Imagen de Factores que
Limitan Respuesta a la Terapia
• Hipoxia– Efectos Directos: resistencia a
radiacion y quimioterapia
– Indirectos: Inestabilidad genetica
• VEGF, mutacion del p53
• Resistencia Multi Medicamentosa(MDR)
– via P-glicoproteina
– Requerimiento de Alta energia
$$$$$$$$$$$$$$$$$$$$$$
• Citrato de GALIO 67 3,3 mCi = 1176 $
• Cada mCi adicional = 351$
• FDG –f18 15 mCi = 1350$
• Cada mCi adicional = 98$• Cada mCi adicional = 98$
• Centellografia osea corporal = 1500$ +
material radiactivo = 680$ =2180 $
Factores en la Respuesta y la Resistencia
Receptores Receptores
de de
superficiesuperficie
OctreotidoOctreotido
Ritmo Ritmo
ProliferativoProliferativo
Timidina & Timidina &
AnalogosAnalogos
Ritmo Ritmo
GlicoliticoGlicolitico
FDGf18FDGf18
HipoxiaHipoxia
FMISO, EF1, FMISO, EF1, OctreotidoOctreotido
FMISO, EF1, FMISO, EF1,
ATSMATSM
Bombas de Bombas de
EflujoEflujo
MIBI, MIBI,
(Verapamilo, (Verapamilo,
Colchicina)Colchicina)
ReceptoresReceptores
NuclearesNucleares
FES, FDHTFES, FDHT
Clinical History
A 14-year-old girl was diagnosed with osteosarcoma of the lower end of the right femur. Chemotherapy was
recommended prior to surgery to amputate the right leg.
Imaging Findings
NUCLEAR MEDICINE PET/CT: January 2007
IMAGING FINDINGS: The initial PET/CT scan in January 2007 showed a hypermetabolic primary tumor with slight
lateral soft tissue extension but without skip lesions or metastases.
Treatment
The patient was started on chemotherapy with a follow-up PET/CT scan recommended for evaluation
before surgery was scheduled to amputate the right leg.
Follow-up Imaging Findings
NUCLEAR MEDICINE PET/CT: April 2007
IMAGING FINDINGS: The follow-up PET/CT scan performed in April 2007 after her initial
chemotherapy, showed gross decrease in uptake in the primary tumor, suggesting excellent response
to chemotherapy. The standard uptake value (SUV) decreased from 8.0 to 1.0.
• Treatment
Due to the PET/CT findings the surgical plan was altered and a local resection with limb salvage
was performed instead of amputation.
• Dr. Helen Nadel, BC Children's Hospital and BC Cancer Research Centre, Vancouver, Canada
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