non-pet tumor imaging p6_i-131 mibg
TRANSCRIPT
Jiraporn Sriprapaporn, M.D.
Nuclear Medicine
Siriraj Hospital
Mahidol University
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: Diff thyroid cancer (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
Non-PET Oncologic Imaging_Jiraporn
• I-131 or I-123 Metaiodobenzylguanidine
• Noradrenaline analog
• Localizes in adrenergic tissues, catecholamine-producing tumors & their metastases
• First synthesized by Wieland et al. In 1979
• Also known as adrenal medullary imaging
Non-PET Oncologic Imaging_Jiraporn
• Patient Preparation:
– Withdrawal of drugs interfering MIBG uptake
– Lugol’s solution to block thyroid uptake of free iodide
• I-131 MIBG: 0.5-1 for PED, 1-2 mCi for adults, slowly injected
• Imaging at 24,48, (72) hrs pi.
• Normal uptake: Liver, spleen, salivary gls, myocardium, adrenal medulla, colon, bladder, (thyroid)
• Excretion: Kidneys, large bowel
Non-PET Oncologic Imaging_Jiraporn
2010 EANM/SNMMI Guideline
Non-PET Oncologic Imaging_Jiraporn
Thyroid Blockade in Adults
Compound Formulation Daily dose
Potassium iodate Capsules 170 mg
Potassium iodide Capsules 130 mg
1% Lugol’s Solution 1 drop/kg to a maximum of 40
drops (20 drops twice a day)
Potassium perchlorate Capsules 400 mg
2010 EANM Guideline
Non-PET Oncologic Imaging_Jiraporn
Drug interaction with MIBG uptake
• Cardiovascular & Sympathomimetic drugs
– Antiarrhythmics
– Combined /β blockers
– Adrenergic neurone blockers
– Ca channel blockers
– Inotropic sympathomimetics
– Vasoconstrictors symp.
– Β stimulants
– Nasal decongestants
• Neurological drugs
– Antipsychotics
– Tricyclic antidepressants
– Sedating antihistamine
– Opioid analgesics
– CNS stimulants
2010 EANM Guideline
√ Prazosin (-1 antagonist)
Non-PET Oncologic Imaging_Jiraporn
• Pheochromocytoma/Paraganglioma*
• Neuroblastoma*
• Medullary thyroid carcinoma (MTC)
• Carcinoid tumor
• The specificity in diagnosis has remained above 95%.
• The sensitivity has varied with the nature of the tumor: close to 90% for intra-adrenal pheochromocytomas but 70% or less for PGLs. [SNM 2012, PMID: 22475426]
Non-PET Oncologic Imaging_Jiraporn
Incidence of Pheochromocytomas
• Any age, male ~ female
• It is estimated that 1 to 8 (0.0001%–0.0008%) cases of pheochromocytoma occur per million persons annually;
– The incidence of pheo increases with advancing age, with the prevalence approaching 0.1% in elderly persons.
– The prevalence of pheo is about 4%-6.5% in patients who have an incidental adrenal tumor.
– The incidence of genetic predisposition to pheo is between 10% and 20% in patients diagnosed with an apparent pheochromocytoma.
– This tumor is found in up to 5% of patients evaluated for hypertension with suggestive clinical symptoms (eg, headache, diaphoresis, palpitations).
Mary Ann Nguyen & Martin, Gary D. Hammer, 2006 - file:///D:/1_ACAD%203/2006_Pheo_Update.pdf
Non-PET Oncologic Imaging_Jiraporn
Pheochromocytoma (A disease of 10%)
• Malignant (90% are benign)
• Bilateral (90% are arise in just one of the two adrenal glands)
• Extra-adrenal (90% occurs in the adrenal gland)
• In Children (90% are in adults)
• Familial (10% will have a family member)
• Recur (10% or slightly less, will come back 5 to 10 years later)
• Associated with MEN syndromes (patients with rare syndromes of endocrine tumors.)
• Present with a stroke (10% of these tumors are found after the patient has a stroke)
[Classic Sx or TRIAD : Headache, palpitation, sweating]
http://www.endocrineweb.com/
Non-PET Oncologic Imaging_Jiraporn
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)
Non-PET Oncologic Imaging_Jiraporn
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
Non-PET Oncologic Imaging_Jiraporn
Pheo & associated hereditary syndromes
von Hippel-Lindau Syndrome (vHL)***
• Autosomal dominant (AD)
• Patients with vHL can develop pheochromocytomas (often bilateral), paragangliomas, retinal angiomas, CNS hemangioblastomas (brain tumors), RCC, renal and pancreatic cysts, pancreatic endocrine tumors, and epididymal cystadenoma.
• Mutations in the vHL gene, on chromosome 3.
• In some families with vHL, pheochromocytoma is the only sign of the syndrome.
• Overall, about 10 to 20% of vHL patients will develop pheochromocytomas.
• Bilateral tumors may present synchronously (i.e. at the same time) or separately over the course of many years.
MEN2A and 2B syndrome***
• AD
• Mutations in the RET gene are responsible for tumor development in
MEN2. 2 forms
• MEN 2A, pheochromocytomas are usually bilateral but may be
asynchronous (i.e. develop separately over time). They occur in
about 50% of MEN2A patients and are associated with MTC and
hyperparathyroidism
• MEN2B (accounts for 5% of MEN2 cases) includes
pheochromocytomas (usually bilateral), MTC, mucosal neuromas
(bumps on the lips, tongue, and eyelids), thickened corneal nerves
over the front of the eye, intestinal ganglioneuromatosis, and a
marfanoid body habitus
Neurofibromatosis type 1 (NF1)
• NF1 is also known as von Recklinghausen's disease.
• Mutation in chromosome 17
• NF1 is characterized by café au lait lesions (i.e. coffee-colored skin spots)
and tumors arising from nerve cells in the skin.
• Pheochromocytoma can occur in up to 5% of cases.
• They can be both in the adrenal and outside of the adrenal, but are rarely
bilateral.
Familial Paraganglioma Syndrome
• Pheochromocytomas can also occur (albeit rarely) in association with
familial paraganglioma syndromes
• Mutations in the succinate dehydrogenase (SDH) gene.
• Mutations in the B, C, and D parts of the SDH gene lead to different forms
of the disease.
Non-PET Oncologic Imaging_Jiraporn
Genetic testing should be considered if ..
a patient has one or more of the following:
• Diagnosis at younger than 50 years old
• Bilateral pheochromocytomas
• Paraganglioma
• Family history of pheochromocytoma or paraganglioma
• Family history of the syndromes previously described
• Other signs or symptoms of the syndromes previously described
Non-PET Oncologic Imaging_Jiraporn
LAB Investigations
• Plasma metanephrine testing has the highest sensitivity (96%) for detecting a pheochromocytoma, but it has a lower specificity (85%).[28]
• In comparison, a 24-hour urinary collection for catecholamines and metanephrines has a sensitivity of 87.5% and a specificity of 99.7%.[29]
http://emedicine.medscape.com/article/124059-workup
Non-PET Oncologic Imaging_Jiraporn
Biochemical diagnosis of pheochromocytoma
Tests Sensitivity Specificity
Plasma free metanephrine1 96% 85%
24-hr urine metanephrine2 87.5% 99.7%
Plasma normetanephrine
24-hr normetaneohrine
24-hr urine VMA
http://emedicine.medscape.com/article/124059-workup
1. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, et al. Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA. 2002 Mar 20. 287(11):1427-34. 2. de Jong WH, Eisenhofer G, Post WJ, Muskiet FA, de Vries EG, Kema IP. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab. 2009 Aug. 94(8):2841-9.
Non-PET Oncologic Imaging_Jiraporn
Biochemical Diagnosis of Pheochromocytoma: Which Test is Best?
Lenders JW, Et Al. JAMA 2002 PubMed PMID: 11903030
Tests Sensitivity [95% CI] Specificity [95% CI]
Plasma free metanephrines 99% [96%-100%] 89% [87%-92%]),
Urinary fractionated
metanephrines 97% [92%-99%] 69% [64%-72%]
Plasma catecholamines 84% [78%-89%] 81% [78%-84%]
Urinary catecholamines 86% [80%-91%] 88% [85%-91%]),
Urinary total metanephrines 77% [68%-85%] 93% [89%-97%]);
Urinary VMA 64% [55%-71%] 95% [93%-97%]
Catecholamines & metabolites
Non-PET Oncologic Imaging_Jiraporn
Detecting Pheochromocytoma: Defining the most sensitive test.
Guller U et al. 2006
Non-PET Oncologic Imaging_Jiraporn
Pheochromocytoma, An Update
• The “rule of 10s” is an outdated axiom that can no longer be used as an epidemiologic guide to pheochromocytomas.
• Genetic testing should be performed in the following groups:
– patients with a family history of pheochromocytoma,
– patients with bilateral or multifocal tumors or malignant or extra-adrenal pheochromocytoma, and
– patients who are aged 50 years or younger when diagnosed with pheochromocytoma.
• Plasma free metanephrine levels are the biochemical test of choice for excluding pheochromocytomas. (sen 99%)
• CT and MRI should be used as first-line imaging modalities for localizing pheochromocytomas.
• Radiolabelled MIBG radionuclide scan is useful for confirmation of pheochromocytoma and evaluate the extent of disease.
Mary Ann Nguyen & Martin, Gary D. Hammer, 2006 - file:///D:/1_ACAD%203/2006_Pheo_Update.pdf
Non-PET Oncologic Imaging_Jiraporn
Interpretation-Pitfalls
• Causes of false-negative results
– Lesion size,
– Tumor biology ( radiotracer avidity),
– Physiological uptake masking cancer lesions,
– Pharmaceutical interference, etc.
• Causes of false-positive results
– Artifacts (eg. contamination-planar images),
– Uptake due to physiological processes (misleading),
– Benign uptake, etc.
Non-PET Oncologic Imaging_Jiraporn
I-131 MIBG Scan in Right Pheochromocytoma
A. Whole-body I-131 MIBG images
B. I-131 MIBG static images with renal ROIs (Tc-99m DMSA)
• Typical location of adrenal mass = superomedial aspect of the kidney
24 hrs 48 hrs
Anterior Posterior Anterior Posterior
160905
A
Anterior Posterior
B
Non-PET Oncologic Imaging_Jiraporn
I-131 MIBG SPECT/CT Images in Right Pheochromocytoma
Anterior Posterior
SPECT/CT
071011
Non-PET Oncologic Imaging_Jiraporn
21 F, VHL with Family Hx of Pheo (Dad) Bilateral Pheochromocytoma
APD 3-7-15
Non-PET Oncologic Imaging_Jiraporn
70 M, Paraganglioma Retroperitoneal nodule, 3x3x2 cm.
CW 28-4-15
Non-PET Oncologic Imaging_Jiraporn
Malignant Paraganglioma with Multiple Liver and Bone Metastases, preop
I-131 MIBG Scan
Anterior Posterior
SPECT/CT images-Preop
CL 3-12-2009
Non-PET Oncologic Imaging_Jiraporn
Malignant Paraganglioma w Multiple Liver & Bone Metastases, postop.
[Before & After 1st I-131 MIBG Rx]
20-1-2010 15-2-2010
Diagnostic I-131 MIBG scan Posttherapeutic I-131 MIBG scan
Non-PET Oncologic Imaging_Jiraporn
• Neuroblastoma (NBM) is an embryonal malignancy of the sympathetic nervous system, typically occurring in children younger than 4 years of age.
• 70% of tumors originate in the retroperitoneal region, from the adrenal or the abdominal sympathetic chain, and 20% occur in the chest, derived from the thoracic sympathetic chain.
• At the time of Dx, > 50% of patients present with metastatic disease typically involves LN, liver, bone, and bone marrow.
[common locations of bone metastases are in the metaphyseal area of long bones]
The Requisites
Non-PET Oncologic Imaging_Jiraporn
Sen & spec
• Radiolabelled MIBG sensitivity for detection of neuroblastoma is > 90%, with specificity of 95%.
• MIBG is much more specific than bone scan
• Can evaluate both bony and soft tissue (solid organ) metastases.
• Combined bone scan and MIBG scan highest sensitivity for
metastatic disease.
Clinical Indications
• The study is used for staging, detecting metastatic disease, restaging, and determining patient response to therapy. (MIBG is very sensitive)
The Requisites
Non-PET Oncologic Imaging_Jiraporn
• Girl, 3 yo.
• Neuroblastoma stage IV with multiple bone metastases 2-44
• Pretreatment
• Staging
ANT POST
Non-PET Oncologic Imaging_Jiraporn
• Girl, 3 yo.
• Neuroblastoma stage IV with multiple bone metastases (2-44)
• S/P 4 courses of chemotherapy (induction)
• F/U after Rx
ANT POST ANT POST
28-2-44 (PreRx) 6-6-44 (PostRx)
Non-PET Oncologic Imaging_Jiraporn
I-123 MIBG SPECT/CT & Bone Metastasis in NBM
• Axial I-123 MIBG SPECT/CT
images demonstrating focal
uptake in a metastatic focus
in the T12 pedicle. (A: SPECT,
B: Fused SPECT/CT, C: CT )
B C
Sharp SE et al. SNM 2011