THE PARATHYROID GLAND THEORY AND NUCLEAR MEDICINE PRACTICE

THE PARATHYROID GLAND THEORY AND NUCLEAR MEDICINE PRACTICE George N. Sfakianakis MD Professor of Radiology and Pediatrics Director, Division of Nuclear Medicine UM/JMMC Miami FL October 2009

ENDONCRINE GLANDS RADIOISOTOPE IMAGING AND THERAPY THYROID GLAND TRAPPING MECHANISM : 99m Tc-0 4 Na (γ) IODINATION: 123 I (γ), 131 I (β), 125 I (Auger e - ) METABOLISM: 18 FDG, 201 TI (x), 99m TcMIBI (γ) PARATHYROIDS METABOLISM (K): 201 TI(x), 99m Tc-MIBI (γ) ADRENAL CORTEX STEROIDOGENESIS: 131 I( 123 I) CHOLESTEROL ADRENAL MEDULLA NORADRENALIN SYNTHESIS: 131 I( 123 I) MIBG PITUITARY GLAND RECEPTORS: 18 F-BROMOCTYPTINE 111 In- 99m Tc-OCTREOTIDE RVH (RENIN) ACE-INHIBITORS 99m Tc-MAG 3 /LASIX SOMATOSTATIN RECEPTOR IMAGING: 111 In-OCTREOTIDE

PARATHYROID GLANDS ANATOMY-EMBRYOLOGY-PHYSIOLOGY

LOCATION OF ORTHOTOPIC AND ECTOPIC PARATHYROID GLANDS AND ADENOMAS

HYPERPARATHYROIDISM (1) PRIMARY: TUMORS (ADENOMAS-CARCINOMAS) HYPERPLASIA (2) SECONDARY: RENAL FAILURE => HYPERPLASIA

PARATHYROID GLAND SCINTIGRAPHY 201 Thallium+ 99m Tc-Pertechnetate(TcPTC) 99m Tc-SESTAMIBI+ 123 INa or TcPTC 99m Tc-SESTAMIBI 30min+120min imaging SPECT/CT ( 99m Tc-SESTAMIBI 30min+2hr)

PARATHYROID IMAGING RADIOPHARMACEUTICALS Single Photon agents for Planar and SPECT 201 Thallium 99m TcSestamibi Tl + Tl

PARATHYROID IMAGING RADIOPHARMACEUTICALS Pump Mitochondria Thallium Sestamibi

A patient is evaluated with clinical and laboratory finding suggesting hyperparathyroidism A Thallium / Technetium study is performed to see parathyroid adenoma

PARATHYROID ADENOMA (Primary) with Thallium-201 / Tc-99m Pertechnetate Subtraction Tl visualizes Tc-PT visualizes the Thyroid and Only the Thyroid the Parathyroid Adenoma Thallium Tc-Pertechnetate Subtraction Images show only the Parathyroid Adenoma Subtraction Images

A patient is referred for parathyroid adenoma The patient had right hemi-thyroidectomy to remove (50% by chance) an unidentified potentially orthotopic parathyroid adenoma The patient had a Thallium-201 / Tc-99m-Pertechnetate study now

PARATHYROID ADENOMA (Primary) MEDIASTINAL THALLIUM PERTECHNETATE Salivary glands Hemi-thyroid Mediastinal parathyroid adenoma

Enters Sestamibi (MIBI) Sestamibi has higher Sensitivity than Thallium for Parathyroid adenomas but also While Sestamibi is washed out from the thyroid gland it stays in the parathyroid O Docherty et al JNM 1992, 33:313-318

EARLY AND LATE IMAGING WITH MIBI PARATHYROID LESION: AREA OF PRESISTENT ACTIVITY LOCALIZATION RATE 90% (19/21) FOR ADENOMA Taillefere et al JNM 1992; 33:1801-1807

(Surgical) Therapy of PTH-Adenomas the Miami Approach The effort of the surgeon: Localization and Complete Excision of all Hyperfunctioning Tissue (this can be a difficult and lengthy operation) Hypothesis: Exact Preoperative Localization by MIBI-SPECT helps identify easier and faster the Adenoma(s) Intraoperative monitoring of PTH confirms the total excision of all abnormal tissue These may improve results and shorten the operation

2

Protocol for Parathyroid Adenoma Localization with 99m Tc-SESTAMIBI at UM/JMH 99m Tc-SESTAMIBI 20 mci IV Planar and SPECT acquisition (Picker/Trionix) immediately and at 2 hours post injection Routine Reconstruction and Reprojection mode Review of SPECT in the Reprojection mode its 34 images and the rotating 3-D version

Planar 99m Tc-SESTAMIBI Study 30 min 2 hr SPECT Reprojection mode = 34 images

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) RIGHT, LOWER POLE, WITHIN THE THYROID GLAND MIBI Volume Images Salivary glands EARLY Thyroid gland Heart Parathyroid adenoma LATE ANT R. LAT Strap Muscles ANT R. LAT

PATHOLOGIC FOCI PARATHYROID ADENOMAS/HYPERPLASIAS THYROID TUMORS (BENIGN AND MALIGNANT) [ 99m Tc0 4 Na ( 123 INa) may exclude functioning (benign) thyroid tumors but not carcinomas ] MEDIASTINAL/NECK/CHEST TUMORS/LYMPH NODES [ 67 Ga may exclude lymphomas, lung cancer]

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) LEFT, LOWER, POSTERIOR, ADJACENT TO THE SPINE MIBI Planar Images Early Late MIBI Volume (reprojection) Images Early Late Parathyroid adenoma But where exactly is it located? Anterior LAO Left Lateral

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) LEFT, CAUDALLY AND IN THE SAME PLANE WITH THE THYROID (ECTOPIC IN THE THYMUS GLAND) MIBI Planar Images Early Late MIBI Volume (reprojection) Images Early Late Parathyroid adenoma But where exactly is it located? Anterior LAO Left Lateral

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) RIGHT, LOWER, INSIDE THE THE THYROID AND THYROID ADENOMA LEFT, UPPER MIBI Planar Images MIBI Volume (reprojection) Images ANT LAO L LAT EARLY EARLY LATE Questionable Findings There is a lesion on the left There is also a lesion on the right LATE

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) FALSE NEGATIVE STUDY MIBI Planar Images Early Late MIBI Volume (reprojection) Images Early 7 / 7 Late 7 / 21 Right Lateral RAO Anterior

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

TWO PARATHYROID ADENOMAS (Primary) RIGHT, UPPER AND LOWER, WITHIN THE THYROID MIBI Planar Images MIBI Volume (reprojection) Images There is a lesion on the right upper There is a lesion on the right lower There is a LN uptake

MODE OF REPORTING All abnormal foci in the neck and mediastinum present early and active late are reported Upper limit: thyroid cartilage (strap muscles?) Lateral limit: 1cm lateral to thyroid margin Inferior limit: myocardium Foci are ordered by intensity of activity and size of the abnormality and are localized in relation to the thyroid The surgeon reviews the study preoperatively in consultation with the nuclear specialist

A patient s/p renal transplant is referred for Tc-Sestamibi (MIBI) study for parathyroid hyperplasia (hypercalcaemia / high PTH)

PARATHYROID HYPERPLASIAS (Secondary) MIBI Planar Images MIBI Volume (reprojection) Images Early Late Early Late There are two lesions planar Muscle uptake There are two lesions tomo

SECONDARY HYPERPARATHYROIDISM All 4 parathyroid glands are hyperplastic

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) ECTOPIC (MIDDLE MEDIASTINAL) MIBI Planar MIBI SPECT Volume(reprojection) EARLY LATE ANT LAO L LAT EARLY Ectopic Parathyroid Adenoma Bone marrow How deep is it located? LATE Ectopic Parathyroid Adenoma Retrosternal

Additional scintigraphic studies for more Precise Localization and Tissue Characterization To Better Localize Mediastinal Lesions: a) Simultaneous Sestamibi, Skeletal and Blood Pool SPECT: 30 mci MDP the night before (Bone Scan) 20 mci SESTAMIBI 5(8) mci Human Serum Albumin b) Sestamibi SPECT/CT To Differentiate Lymphoma from PTH Adenoma Sequential SESTAMIBI-GALLIUM SPECT (Gallium showed only lymphoma)

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) ECTOPIC (LOWER MEDIASTINAL) Tc-SESTAMIBI Tc-SESTAMIBI + Tc-HSA(for Blood Pool) Ectopic Adenoma Ectopic Adenoma on the ascending aorta

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcaemia / high PTH)

PARATHYROID ADENOMA (Primary) ECTOPIC PLANAR MIBI EARLY LATE To Better Localize Mediastinal Lesions: a) Simultaneous: Sestamibi, Skeletal and Blood Pool SPECT: b) Sestamibi SPECT/CT

PARATHYROID ADENOMA (Primary) Ectopic (Mediastinal, middle) Under the Aortic Arch Adenoma Skeleton Aortic Arch

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma S/P Hemithyroidectomy (hypercalcemia / high PTH)

PARATHYROID ADENOMA (Primary) ECTOPIC PLANAR MIBI EARLY LATE Early Study Late Study

PARATHYROID ADENOMA (Primary) ECTOPIC Early Study PLANAR MIBI EARLY LATE Late Study

PARATHYROID ADENOMA (Primary) Ectopic (Mediastinal, middle) Under the Aortic Arch

A patient is referred for SPECT/CT Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcemia / high PTH)

PARATHYROID ADENOMA (Primary) ORTHOTOPIC Early Study

PARATHYROID ADENOMA (Primary) ORTHOTOPIC PLANAR MIBI EARLY LATE Late Study

A patient is referred for Tc-Sestamibi (MIBI) study for parathyroid adenoma (hypercalcemia / high PTH)

PARATHYROID ADENOMA (Primary) In a patient with Lymphoma The use of Gallium for differentiation Tc-Pertechnetate Tc-SESTAMIBI ANT LAO L LAT Lymphomas. Is there an adenoma? Lymphomas The Adenoma

PROTOCOL OF OPERATION PERIPHERAL VENOUS BLOOD IS DRAWN/PREPARED (FOR BSL-PTH) THE MOST INTENSE/LARGER FOCUS IS EXCISED (RESECTION-1) PERIPHERAL VENOUS BLOOD IS DRAWN 5 min LATER (FOR PRS-PTH) (T1/2 of PTH in the blood is 2-3 min) IF PRS-PTH <1/2 BSL-PTH, OPERATION COMPLETED WHEN ADDITIONAL LESIONS EXIST PTH REMAINS HIGH THE SURGEON EXCISE THE NEXT MOST INTENSE/LARGE FOCUS AND PERIPHERAL VENOUS BLOOD IS DRAWN FOR PRS-PTH REPEATEDLY,UNTIL PRS-PTH <1/2 BSL-PTH

QUICK INTRAOPERATIVE PTH ASSAY(qPTH) IMMUNORADIOMETRIC (12 min) IRMAIMMUNOCHEMILUMINESCENCE (5 min) PTH HAS SHORT HALF LIFE (3-4 min) DRAW BLOOD BEFORE AND 5 min AFTER EXICISION SPIN/INCUBATE COUNT IN THE OPERATING ROOM RESULTS AVAILABLE BEFORE PATHOLOGY REPORT IF THERE IS A 50% DROP IN qpth, AWAKE PATIENT

THE ROLE OF PREOPERATIVE SPECT 99m Tc-SESTAMIBI TUMOR LOCALIZATION AND INTRAOPERATIVE PTH MONITORING IN PARATHYROIDECTOMY G. N. Sfakianakis, J. Foss, M. Georgiou, G. Irvin III S. Levis-Dusseau, S. Chandarlapaty University of Miami School of Medicine, Miami, FL

MIBI-SPECT/RPJ IN PARATHYROIDECTOMY THE UM EXPERIENCE Preoperative scintigraphy (MIBI-SPECT/RPJ) Intraoperative measurements of PTH (QPTH) Total patients studied: 75 Patients operated: 58 (1 0 :52,2 0 :4,MEN:2) SPECT: Sensitivity = 94%, Specificity = 92% SPECT+QPTH: 98% cure rate in 30%less time

INITIAL RESULTS OF SCINTIGRAPHY 36 PATIENTS (36 STUDIES) WITH PRIMARY HYPERPARATHYROIDISM FINDINGS SPECT PLANAR POSITIVE 32 26 CONFUSING/QUESTIONABLE 1 8 NEGATIVE 3 6 THERE WERE 2 CASES WITH MEDIASTINAL TUMORS

CORRELATION OF 99m Tc-SESTAMIBI IMAGING WITH OPERATIVE FINDINGS OPERATED: 22 PATIENTS (JAN. 5, 1994) RESULTS SPECT/R PLANAR ACCURATE LOCALIZATION 21 16 CONFUSING IMAGE 1 5 FALSE NEGATIVE - 1

RESULTS (PRELIMINARY) TOTAL PATIENTS : 49 FOCI IDENTIFIED: ONE TWO THREE FOUR MEDIASTINAL PATIENTS : 35 5 6 3 4 OPERATED PATIENTS: 39 TUMORS EXCISED: ONE TWO THREE MEDIASTINAL PATIENTS : 24 3 1 1 TUMORS NOT FOUND: 1 (MEDIASTINAL,UNACCESSIBLE)

RESULTS (PRELIMINARY) CON T TUMORS EXCISED BUT NO CURE: 3 (SCAN IDENTIFIED ADDITIONAL TUMOR BUT ASSAY/INTERPRETATION ERROR) LESIONS MIMICKING PARATHYROID ADENOMA: 3 1. THYROID ADENOMA 2. LYMPH NODES (NORMAL/LYMPHOMA)

USEFULNESS OF SPECT SESTAMIBI FOR LOCALIZATION OF PARATHYROID ADENOMAS IT IS MORE SENSITIVE THAN PLANAR IMAGING IDENTIFIES EXACT LOCATION OF LESION (DEPTH) AND RESULTS IN FASTER RECONGNITIION OF LESIONS AND SHORTENING OF THE OPERATION TIME BY 50% AN AVERAGE TIME OF SAME SURGEON 90--> 36 min A MINIMUM OPERATIVE TIME (SKIN TO SKIN) 13 min ENABLES OPERATION ON AN OUTPATIENT BASIS

CONCLUSION THE PREOPERATIVE LOCALIZATION OF PARATHYROID ADENOMAS WITH SPECT 99m Tc-SESTAMIBI AND THE INTRAOPERATIVE QPTH MEASUREMENT RESULTED IN BETTER PATIENT CARE AND THEY WERE ALSO COST EFFECTIVE REDUCING OPERATING TIME AND HOSPITALIZATION