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IAEA Consultant’s Meeting: Clinical Use of Gamma Probes in Cancer Management
Radioguided Surgery: Open Issues and Perspectives
Giuliano MarianiRegional Center of Nuclear Medicine
University of Pisa Medical School, Pisa, Italy
Vienna, July 19-21, 2010
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Radioguided Surgery: Definitions•• ComplexComplex ofof prepre-- and and intraintra--operativeoperative proceduresprocedures thatthat implyimplyinteractioninteraction ofof at at leastleast due due disciplinesdisciplines ((NuclearNuclear Medicine and Medicine and SurgerySurgery) ) withwith the the aimaim ofof optimizingoptimizing oncologiconcologic surgerysurgery..
•• CloselyClosely linkedlinked toto the the modernmodern approachesapproaches aimingaiming at at reducingreducingasas muchmuch asas possiblepossible invasivenessinvasiveness ofof surgerysurgery and at and at sparingsparingunnecessaryunnecessary surgeriessurgeries alsoalso in the in the oncologiconcologic domain.domain.
•• TwoTwo mainmain applicationapplication domainsdomains::- Sentinel lymph node biopsy(solid epithelial cancers)- Radioguided occult lesion localization (ROLL).
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Radioguidance
Adding “hearing” (proportional to radio-activity accumulation and directed by distribution) as an extra-sense of the surgeon (in addition to “seeing” and “touch”), with incremental value versus conventional preoperative imaging.
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Radioguidance•• Utilization of probes for intraUtilization of probes for intra--operative detection operative detection of radiation (of radiation (γγ or or ββ++, with or without imaging), with or without imaging)emitted by a tissue of interest that has emitted by a tissue of interest that has preliminarly been preliminarly been ““radiolabeledradiolabeled””..
•• Such detection Such detection ““guidesguides”” the surgeon for faster the surgeon for faster and more accurate identification/localization of and more accurate identification/localization of the tissue to be removed.the tissue to be removed.
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Radioguided Surgery•Sentinel lymph node: Mapping of lymph nodes Mapping of lymph nodes draining the tumor site, after peridraining the tumor site, after peri--tumoral tumoral administration of a lymphoadministration of a lympho--tropic tropic radiopharmaceutical (nonradiopharmaceutical (non--specific).specific).
•ROLL: Localization of a nonLocalization of a non--palpable/nonpalpable/non--visible visible tumor lesion, after administration of suitable tumor lesion, after administration of suitable radiopharmaceutical either intraradiopharmaceutical either intra--tumorally (tumorally (99m99mTcTc--MAA, nonMAA, non--specific) or systemically (tumorspecific) or systemically (tumor--seeking seeking radiofarmaceuticals).radiofarmaceuticals).
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Sentinel Lymph Node Biopsy
• Breast cancer• Cutaneous melanoma• Penile cancer• Head & neck cancer• Gynecologic cancers• Gastrointestinal cancers• Prostatic cancer• Non-Small Cell Lung Cancer• Thyroid cancers• Others?
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ROLL• Breast cancer• Parathyroid tumors• Neuroendocrine tumors• Solitary pulmonary nodules• Locally recurring thyroid cancer• GI cancers (MoAb and 99mTc-MAA)• Bone lesions• [18F]FDG-avid tumors• Others?
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Endoscopic Injection of 99mTc-MAA in Colonic Lesions
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Laparoscopic Gamma-Probe
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Ultrasound-Guided Injection of 99mTc-MAA in Locally Recurring Thyroid Cancer
Pisa Group: Ann Surg Oncol (submitted)
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Ultrasound-Guided Injection of 99mTc-MAA in Locally Recurring Thyroid Cancer
Pisa Group: Ann Surg Oncol (submitted)
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Lesions/pt (mean±sd) 1.7±0.9range 1 – 4
Lesion size, mm (mean±sd) 11±4.5range 4-20
Size ≤ 10 mm 28/59 (47%)Level (Robbins)
II 10III 11IV 16V 4VI 17VII 1
Ultrasound-Guided Injection of 99mTc-MAA in Locally Recurring Thyroid Cancer
Pisa Group: Ann Surg Oncol (submitted)
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ROLL with Tumor-Seeking Radiopharmaceuticals
•• 99mTc-Sestamibi• 111In-Octreotide• 131I-Iodide• 111In-MoAb• 99mTc-Depreotide• 99mTc-Bombesin and other peptides• [18F]FDG• [18F]Fluoro-deoxyuridine• 68Ga-DOTA-TOC• Etc.
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99mTc-Depreotide (2 h)15-mm nodule in upper lobe of right lungCT-guided FNA: undeterminedRadioguided VATS 24 h after 99mTc-Depreotide (700 MBq): Adenocarcinoma.Lesion/background SPECT: 1.8Lesion/background VATS: 2
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Most Recent/Promising Developments in Radioguided
Surgery• Wireless gamma probes• Hybrid imaging (pre-operative)• Intra-operative imaging• Positron-sensitive probes• Probes for high-energy gamma photons• Probes with 3-D tracking and optical/radioactivity fusion (“surgical eye”)
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SPECT/CT with 99mTc-Sulfur colloid for sentinel lymph node biopsy
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SPECT/CT with 99mTc-Sulfur colloid for sentinel lymph node biopsy
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Patient #1Patient #1 Patient #2Patient #2
SPECT/CT with 99mTc-Sestamibi for parathyroid adenomas
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SPECT/CT with 99mTc-Sestamibi in recurrent primary hyperparathyroidism
Ectopic parathyroid adenoma in upper mediastinum
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SPECT/CT with 99mTc-Sestamibi in secondary hyperparathyroidism
(US: hyperplastic right lower parathyroid)
Multiple-gland disease: lower right, upper right (retro-tracheal), and lower left (para-retro-tracheal)
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Radioguided Detection of Cancer
Courtesy of IntraMedical Imaging, Los Angeles, Ca
Colorectal Ca.
1- Probe for high-energy gamma rays:detection of deep-seated tumors
2- Beta-probe for detection of positrons:checking the margins
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The GF&E design
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Electronic Collimation versus Mechanic Collimation
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γ-Locator DXI
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Pisa: Clinical Case 1
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Patient SV, 79-yr old woman
09.04.08: Biopsy left breast
�� PossiblePossible infiltratinginfiltrating cancercancer ((butbut nonnon--diagnostic)diagnostic)
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12.05.08: Lymphoscintigraphy for SLNB
45°°°° Left oblique SPECT/CT
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13.05.08: PET/CT with [18F]FDG
SUVSUVmaxmax 3.7 (primary lesion in left breast)3.7 (primary lesion in left breast)
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13.05.08: Surgery, about 2 h after [18F]FDG and 24 h after 99mTc-Nanocoll
IN VIVO 99mTc IN VIVO 18FSLN 5500 cps Tumor 10600 cpsBackground 655 cps Background 400-500 cps
EX VIVO 99mTc EX VIVO 18F1 SLN 3000 cps Tumor 9030 cps2 SLN 1051 cps Background 400 cpsBackground 400-500 cps Resection bed 400 cps
Intraoperative counts
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Intraoperative Histology
� Infiltrating breast cancerInfiltrating breast cancer(with free margins)(with free margins)
�� LNS (1) : micrometastasisLNS (1) : micrometastasis
AxillaryAxillary dissectiondissection
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Pisa: Clinical Case 2
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Patient CG, 59-yr man
18.06.08 PET/CT: SUVSUVmaxmax 15.8 in 15.8 in CTCT--visiblevisible lesionlesion at at the the leftleft lowerlower lobelobe..
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19.06.08: Surgery, 2-3 h after [18F]FDG
Intraoperative CountsLesion 4700 cps; ex vivo 2300 cpsLesion 4700 cps; ex vivo 2300 cpsLingula 1500 cpsLingula 1500 cpsBackground 500/600 cpsBackground 500/600 cpsCarenal lymph node Carenal lymph node in vivoin vivo 800/1230 cps; 800/1230 cps; ex vivoex vivo 500 cps500 cpsHylar lymph node 600/800 cpsHylar lymph node 600/800 cpsPulmonary vein 500/600 cpsPulmonary vein 500/600 cps
Surrounding healthy tissue Surrounding healthy tissue ex vivoex vivo 200 cps200 cps
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Atypical Left Lower Lobectomy(including part of lingula)
Histology•• Moderately differentiated adenocarcinoma (G2), with mixed Moderately differentiated adenocarcinoma (G2), with mixed features (acinar, bronchofeatures (acinar, broncho--alveolare and solid).alveolare and solid).
•• 13 hylar13 hylar--mediastinal lymph nodes with reactive hypermediastinal lymph nodes with reactive hyper--plasia and anthracosis (but no metastasis).plasia and anthracosis (but no metastasis).
•• Stage: pT2(G2) N0 MxStage: pT2(G2) N0 Mx..
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CSS300 for freehand SPECT
Gamma Detection using conventional gamma probe
Imaging & Navigation bySurgicEye‘s CSS300
freehand SPECT imaging and navigation device
0297
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Spatial localization system of CSS3001. Handle (can be covered to be used sterile)2. Optical camera3. Infrared localization system4. Non-sterile Handle
1
4
32
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Gamma probewith steriletracking target
Sterile patient target
Accessories of CSS300
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Data with tracked non-imaging probeNon-uniform/non-symmetric set
<180° coveredCenter depends on scan< 40 thousand events
Freehand SPECT imaging technologyused in CSS300 during surgery
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Cases of SLNB in Breast CancerCases of SLNB in Breast Cancer3D Imaging and Navigation at the Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa (Italy)
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Setup in the OR
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Case 1: pre-incision image /visualization in 3D (focus on 1st SLN)
1st SLNInjection site
1st SLN
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Case 1: pre-incision image /visualization in 3D (focus on 2 SLNs)
1st SLN
Injection site
1st SLN
2nd SLN
2nd SLN
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Case 1: image after resection of 1st SLN / visualization in 3D
Remaining SLN (2nd)
Injection site2nd SLN
Lymphatic / 3rd SLN?
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Case 2: pre-incision image /visualization in 3D
1st SLNs
Injection site 1st SLNs
Injection site 2nd SLN
2nd SLN
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Case 2: image after resection of 1st SLNs / visualization in 3D
Injection site 2nd SLN
2nd SLN
Injection site
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Case 3: pre-incision image /visualization in 3D
Injection site SLN
Injection site
SLN
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Case 3: image after resection of 1st SLN / visualization in 3D
Injection site
Neglible count rateNeglible remaining radioactivity
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