Non-PET Tumor Imaging p5_Tc-99m MIBI_Parathyroid

Jiraporn Sriprapaporn, M.D.

Nuclear Medicine

Siriraj Hospital

Mahidol University Last updated on 6 Aug 2017

Non-PET Oncologic Imaging_Jiraporn

Radiopharmaceuticals for Non-PET Oncologic Applications

Nonspecific

• Ga-67 citrate:

– Lymphoma

• Tl-201 chloride:

– Bone sarcomas

– Brain tumors

– Thyroid cancer

• Tc-99m sestamibi:

– Breast cancer

– Parathyroid adenoma

– Thyroid cancer

• Tc-99m tetrofosmin: Similar to sestamibi

Tumor-Type Specific

• I-131: DTC (PTC, FTC)

• I-131 MIBG: Neural crest tumors (adrenal medullary imaging)

• Radiolabeled peptides, Somatostatin receptors:

– In-111 pentetreotide (OctreoScan): Neuroendocrine tumors

– Tc-99m HYNIC-TOC: NETs

– Tc-99m depreotide*: Lung cancer

• Radiolabeled monoclonal antibodies:

– Tc-99m arcitumomab (CEA-Scan)*: Colorectal cancer

– In-111 capromab pendetide (ProstaScint): Prostate cancer

REF : modified from The Requisites


• Purpose: To localize the hyperfunctioning parathyroid

gland(s) in cases of hyperparathyroidism before surgery,

making possible minimally invasive surgery.

• The clinical diagnosis of hyperparathyroidism is generally

made by elevated serum Ca, reduced serum PO4-, and

elevated PTH level.


Anatomy:

• 80% of population have 4 parathyroid glands at posterior aspect of thyroid

• Normal gland size: 35 mg • Ectopic parathyroid glands

– Unusual locations: carotid bifurcation, inferior in the mediastinum and pericardium, anterior to the thyroid, and posterior in the superior mediastinum in the tracheoesophageal groove and paraesophageal region

Parathyroid glands (posterior)

Ectopic parathyroid glands


Parathyroid Glands: Embryology

• The superior glands are derived from the 4th pharyngeal pouch and are more constant position in relation to the middle or upper third of the lateral thyroid lobe

• The inferior glands are derived from the 3rd pharyngeal pouch (origin of thymus) they migrate along with

the thymus.


Eutopic Parathyroid Glands

• Eutopic superior parathyroid glands (red dots) are situated posterior to the superior and middle third of the thyroid lobe.

• Eutopic inferior parathyroid glands (blue dot) are posterior, lateral, or anterior to the inferior third of the thyroid

Superior Parathyroid gland

Inferior Parathyroid gland

Eslamy HK, RADGr 2008


Ectopic Parathyroid Glands

• Ectopic superior glands (red dots), from top to bottom

• In the carotid sheath; intrathyroidal; in the tracheoesophageal groove, retroesophageal, or paraesophageal; or posterosuperior mediastinal.

• Ectopic inferior glands (blue dots), from top to bottom

• Submandibular, intrathyroidal, in the thyrothymic ligament, intrathymic (in the neck), or anterosuperior mediastinal; except in intrathyroidal locations, their positions are anterior to those of superior glands.



Hyperparathyroidism (HPT)

• Primary HPT: Adenoma; High Ca, Low PO4

• Secondary HPT: occurs in cases with renal insufficiency Hyperplasia; Normal Ca, high PO4

• Tertiary HPT: occurs in cases with renal failure, one or more glands become autonomous hypercalcemia

Cause of PHPT Percentage Adenoma 85 Hyperplasia 10 Ectopic <5 Carcinoma <1

The Requisites


Pathophysiology of Hyperparathyroidism

• Parathormone (PTH), an 84–amino acid polypeptide hormone, is synthesized, stored, and secreted by the chief cells of the parathyroid glands.

• Hyperparathyroidism: Increased synthesis and release of PTH.

• PTH regulates calcium and phosphorus homeostasis by its action on bone, small intestine, and kidneys.


Primary Hyperparathyroidism (PHPT)

• PHPT is usually a sporadic disease, <5% of cases is hereditary. (MEN1, MEN2A).

• Causes:

– 85% single adenoma, 15% multiple adenomas or hyperplasia. [Fraker DL 2009]

– 90% single adenoma, 4% double adenomas, 6% hyperplasia of multiple glands, and < 1% parathyroid carcinoma [Ruda JM 2005]

– Ectopic parathyroid adenomas are noted in about 10-20% of cases and the anterior mediastinum is the most common location

• Presentation: Asymptomatic (75%–80%) or symptomatic (20%–25%) [Bilezikian JP].

• LAB: High PTH, High Ca, , Low PO4

http://emedicine.medscape.com/article/127351-overview

MEN = Multiple Endocrine Neoplasia


Multiple Endocrine Neoplasia

MEN MEN 1 (Wermer syndrome)

MEN 2

Mutation MEN1 gene RET proto-oncogene

Prevalence 1 in 30,000 individuals 1 in 30,000 to 1 in 35,000 individuals.

Inherited AD AD

http://www.cancer.gov/types/thyroid/hp/medullary-thyroid-genetics-pdq

MEN2- 3 subtypes • MEN2A • MEN2B • Familial MTC (FMTC)


MEN Syndrome_WIKI

• MEN I (3 Ps) -Pituitary, -Parathyroid, -Pancreatic

• MEN 2A (1M,2Ps) -MTC -Pheochromocytoma -Parathyroid

• MEN 2B (2Ms,1P) -MTC, -Marfanoid habitus/Mucosal neuroma -Pheochromocytoma

3P 2P 1M 1P 2M


Parathyroid Localization for Hyperparathyroidism

4D-CT Selective venous sampling MRI

and angiography

http://www.endocrinesurgery.net.au/primary-hpth-diagnosis/

Ultrasound Tc-99m MIBI Imaging CT Scan


Parathyroid Localization Tests

Study Type Sensitivity Specificity

Ultrasound7,10 71-80% 80%

Endoscopic Ultrasound10 71%

CT Scan6,7,17,19 46-80% 88-98%

MRI Scan6,7,24,28 64-78% 88-95%

Thallium-Technetium Scan7,8,16,18 75% 73-82%

Technetium-Sestamibi Scan3 90.7% 98.8%

PET Scan49,51,53,54 80-94%

Angiography & Venous Sampling7 91-95% 96-98%

Venous Sampling Alone11,16,55 70-80%

http://www.rcsed.ac.uk/RCSEDBackIssues/journal/vol47_4/47400003.html


Parathyroid Imaging for PHPT

• US: sen 34-85%, spec 77-98% [2,3,15,18,21].

– The sensitivity falls to about 40% in patients who have prior failed surgical explorations [21AM].

• CT scan: Sen 46-87 %

• MRI: Sen 70-82%, similar to scintigraphy [4,15 AM].

• Nuclear scan: Sen 60-90% for single adenoma, 50% for multiple glands.

• Nuclear scan:

– Norton KS 2002-12356156 : > 500 mg: sen 91%, < 500 mg sen 80%. (scan does not correlate with Ca nor PTH levels.)

– SPECT-early 96%, combined planar 79%, dual-phase MIBI 60% (Lorberboym M, JNM2003)

1. www.auantminnie.com

2. eMedicine : http://emedicine.medscape.com/article/127351-overview


Role of Parathyroid Scintigraphy

• 99mTc-sestamibi assessment has a well defined clinical role in PHPT > SHPT & THPT

– Preop localization: It can identify patients suitable

for focused surgery and is a prerequisite of the minimally invasive radioguided parathyroidectomy.

– Persistent or recurrent disease post surgery, NM is a first line examination before reoperation.

• 99mTc-sestamibi assessment in secondary HPT is not clearly established.

Ectopic parathyroid adenoma Nuclear scan has great benefit !


Guidelines for Parathyroid Scintigraphy

2012


• Single isotope, dual-phase technique

– Tc-99m MIBI or Tc-99m tetrofosmin, early & delayed

• Double isotopes, subtraction technique

– Tl-201 & Tc-99m pertechnetate

– Tc-99m MIBI & Tc-99m pertechnetate

• Combined techniques

A. Tc-99m pertechnetate thyroid only

B. Tl-201 or Tc-99m MIBI thyroid + parathyroid

Parathyroid = B-A

Parathyroid Scintigraphy: Technique

*Same position


Mechanism of Tc-99m MIBI Uptake

• Parathyroid adenomas typically have a very high metabolic rate for their size and show high avidity for labeled MIBI.

• The presence of mitochondria-rich oxyphil cells and increased vascularity presumably accounts for 99mTc-MIBI trapping

• However, a small number of oxyphil cells in some adenomas may account for rapid washout of 99mTc-MIBI from the adenoma.

Lorberboym M, JNM 2003


Sensitivity of Parathyroid Scintigraphy

Parathyroid Adenoma NM Sensitivity Remarks

The Requisites Approach 90% For > 300 mg adenoma

Essentials of NM ∿ 90% Mostly > 500 g

eMedicine - 60-90%

- 50%

- Single adenoma

- Multiple glands

Wong KK, 2015 86% SPECT/CT, Metaanalysis

Cheung K, 2012 78.9% SPECT, Metaanalysis

Ruda JM, 2005

- 88%

- 44%

Systematic review:

- Single adenomas

- Multiglandular

hyperplasia

Norton KS, 2002 - 91%

- 80%

- For > 500 mg

- For < 500 mg adenoma

Parathyroid Hyperplasia

The Requisites ∿ 50-60%

Caldarella C, 2012 58% (spec 93%) Metaanalysis


• Metaanalysis by Cheung K et al, 2012-21710322

– US: Pooled sensitivity and PPV 76.1% (95% CI 70.4-81.4%) and 93.2% (90.7-95.3%),

– Sestamibi-SPECT: Pooled sensitivity and PPV of 78.9% (64-90.6%) and 90.7% (83.5-96.0%)

– Only two 4D-CT studies: Sensitivity and PPV of 89.4% and 93.5%.

precontrast, post-venous-bolus, postcontrast, and delayed imaging, at 30, 60, and 90 sec after the IV bolus.


Subtraction Technique Dual-phase Technique

Giuliano Mariani et al. J Nucl Med 2003;44:1443-1458

Parathyroid Scintigraphy (Dual-tracer, Subtraction Technique : 99mTcO4 & 99mTc MIBI)


Primary Hyperparathyroidism (Dual-phase Tc-99m MIBI Imaging)

(a) Delayed washout in the right inferior parathyroid adenoma

(b) Early washout in a large inferior thyroid adenoma


Early Delayed


Dual-isotope, subtraction techn.

• Persistent hyperparathyroidism

following right lobectomy due to

ectopic parathyroid adenoma

Early & delayed Tc-99m MIBI scan

• Parathyroid adenoma shows increased

Tc-99m MIBI uptake with delayed

washout at right lower pole

Single isotope, dual-phase technique

99mTcO4- 99mTc MIBI

After subtraction


• Parathyroid Adenoma at left inferior pole

Tc-99m MIBI Parathyroid scan & SPECT/CT images.


SPECT/CT: Left Inferior Parathyroid Adenoma

SPECT/CT images on coronal, sagittal, and axial views.



Double Eutopic Right Parathyroid Adenoma: Fused SPECT/CT- coronal image



Ectopic Parathyroid Adenoma in the Mediastinum

Fused SPECT/CT images: Paratracheal mass at the left tracheobronchial angle. Axial CT image depicts an enhancing 12 × 13-mm left paratracheal mass

parathyroid adenoma. Surgery 1.3-g adenoma



SHPT & THPT

• Secondary hyperparathyroidism: serum

calcium is normal and the PTH level is elevated.

•

• Tertiary hyperparathyroidism : excessive

secretion of PTH after longstanding secondary

hyperparathyroidism, hypercalcemia


Secondary Hyperparathyroidism

• Caldarella C et al.2012- 22875577

• RESULTS: 24 studies, 471 cases

• The pooled sensitivity and specificity of Tc-99m MIBI planar parathyroid scintigraphy in detecting hyperplastic glands in SHPT patients were 58 % (95 % CI 52-65 %) and 93 % (95 % CI 85-100 %), respectively, on a per lesion-based analysis.

• Area under ROC curve was 0.75.


Tertiary Hyperparathyroidism

• Most lesions in THPT are multiglandular disease. [Kebebew E, 2004]

– Hyperplasia 33, single adenoma 1

• Tc-99m MIBI scan sensitivity 76% [Loftus KA, 2007]


Causes of False Negative Results

• Small size of parathyroid lesions, < 500 mg.

• Hyperplastic parathyroid glands

• Small number of oxyphil cells

• Rapid wash-out (delayed phase)

• Coexisting thyroid pathology eg. Nodular goiter

• Cystic adenoma [PMC4211770]

• Multiglandular disease*

• Preop normocalcemia*

* Merlino JI, 2003, 12678479


FN planar Tc-99m MIBI scan due to overlying

nodular goiter

• 3D-volume rendered images show a small adenoma attached to posterior aspect of right lower lobe.

Lorberboym M, et al. JNM 2003


Causes of False Positive Results

• Solitary thyroid adenoma - most frequent*

• Multinodular goiter

• Benign or malignant tumors such as breast, lung, and H & N carcinomas, lymph node met. and osseous metastases, as well as bronchial carcinoids.

– Delayed washout of 99mTc MIBI has been described in DTC.

• Motion artifact (subtraction) Early washout in a large thyroid adenoma


Non-PET Tumor Imaging p5_Tc-99m MIBI_Parathyroid

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