KRNM FN BRNO Nuclear medicine I. —Gama emiters ¡99mTc, 123I, 81mKr, 111In ¡Detects 1 photon ¡Planar scintigraphy (sumation) or SPECT (tomographic) ¡Static x dynamic ¡Possible hybrid imaging SPECT/CT —Beta+ emiters ¡18F, 68Ga, 11C ¡Detects 2 photons ¡Tomographic method ¡Always hybrid imaging PET/CT or PET/MRI ¡ —Beta- and alfa emiters ¡131I – thyroid carcinoma, hyperthyreosis ¡177Lu – metastatic prostate cancer, NETs ¡90Y – synovectomy ¡223Ra (alfa) – prostate cancer bone mts Nuclear medicine —Medical specialty using radiopharmaceuticals for diagnostic and therapeutic purposes — —Diagnostics - imaging the distribution of the tracer in the body ¡Scintigraphy (planar, tomographic=SPECT) and PET ¡Static or dynamic examinations ¡ —The tracer uptake is related to biochemical process and function within tissue/organ/body – scintigraphies are referred to as functional imaging techniques, not showing anatomic details — —Therapeutic methods – targeted radiotherapy based on the distribution of a carrier bound to a suitable radionuclide (beta-, alfa emitter) – 131I, 223Ra, 177Lu, Sr, Sm, Re, 90Y, Er Bone scintigraphy —One of the most commonly used method — —Principle: When tracer is injected intravenously, is taken up by adsorbtion onto the surface of bone, distribution in the skeleton is based on differencies in regional perfusion (vascularity) and bone turnover as well as other factors – non specific!!! — —High sensitivity, small specifity (clinical context, patient´s history, SPECT, SPECT/CT) — —RP: technetium-labeled bisphosphonates (99mTc-MDP), analogs of some components of the mineral portion of bone ¡(alternatively - 18F-NaF for PET imaging ) — —Imaging technique: wholebody planar image in anterior and posterior view 2-4h after RP administration, SPECT or SPECT/CT , 3-phase protocol — Bone scan — skelet3 skelet2 Bone scan scinti kosí kojenec.png scinti kostí děti.png Bone scintigraphy —Indications: — -Metastatic bone disease, primary bone tumors -Osteomyelitis (mostly periferal bones) -Evaluation of prosthetic joints for loosening and infection — -Skeletal trauma, stress fructures -Metabolic bone disease : Morbus Paget, hyperparathyroidism -Evaluation of bone pain in patients with normal radiographs, evaluation of the significance of an incidental bone finding on radiographs, determination of biopsy site Bone scintigraphy —High sensitivity - predominantly osteoblastic sites show increased activity (hot spots), whereas mainly osteoclastic or lytic lesions can be difficult to detect (cold lesions) – tumors that are predominantly lytic have lower sensitivity — —Highest sensitivity for prostate cancer, high sensitivity for breast and lung cancer, low sensitivity for multiple myeloma, thyroid cancer, renal carcinoma….. — —Bone scan vs FDG PET ¡Higher sensitivity of scintigraphy in osteoplatic metastases ¡Higher sensitivity of PET in osteolytic lesions — —Metastatic breast cancer —Metastatic prostate cancer Bone scan skelet1 SK62 SK62A —RCC —Osteosarcoma grawitz tu.png sarkom femuru.png Bone scan Bone scan – SPECT/CT boneCT1 Bone scan– SPECT/CT Lung cancer Paget disease paget.png —The pelvis is the most commonly involved site, followed by the spine, skull, femur… Track sign hypertr.png —Hypertrophic osteoarthropathy — —Increased uptake in the cortices of the femora and tibiae — —Commonly seen in patients with bronchogenic carcinoma, can be seen in other pulmonary conditions Bone scan : Erdheim –Chester disease erdheim.png —Non Langerhans-cell histiocytosis (rare disease) — —Bone leasions are typically symmetrical, sclerotic and involve long bones (with prominent uptake on scan) Infection imaging methods —3-phase bone scintigraphy – bones only! — —Radiolabeled leukocytes —Radiolabeled antigranulocyte monoclonal antibodies — —18F-FDG PET — — — —Galium imaging (67 galium citrate) – has very limited role today 3-phase bone scintigraphy —Indication: differentiation between eosteomyelitis and cellulitis (especially in periferal skeleton), evaluation of joint replacement complications (aseptic loosening or infection) — —Imaging protocol: —I. Flow phase: dynamic 2- to 5-second images of the area of interest for 60 seconds after bolus injection —II. Blood pool and soft tissue phase = immediate static images for time (usually 5 minutes), followed dynamic phase —III. Skeletal phase : Delayed images at 2-4 hours after injection —SPECT/CT increasis specifity — —Withouth underlying bone pathology negative study result exludes osteomyelitis with high degree of certainty —With underlying bone pathology (recent trauma, tumor..) is still sensitivity very high, but specificity only 30-50% — 3-phase bone scintigraphy zánět.png 3-phase bone scintigraphy uvolnění endoprotézy.png Radiolabeled leukocytes —Leukocyte imaging using in vitro labeling with 111Indium or 99mTc is the nuclear medicine gold standard for diagnosing most infection — —Principle: leukocytes are attracted to the site of inflammation – acitive migration, uptake is not specific for infection, may occur in any inflammatory process that incites the leukocytes response — —Leukocytes are isolated from about 60ml anticoagulated blood, labelled in vitro, effectiveness depends on viability, thus is essential to avoid damage to the cells —(If not possible to label enough leukocytes, examination with radiolabeled antigranulocyte monoclonal antibodies is possible, needs HAMA test, imaging protocol is same) — —Imaging protocol: wholebody image in anterior and posterior view at 4 and 24 hours after injection + SPECT/CT , early imaging of the abdomen at 1- 2 hours after injection is obtain in case of inflammatory bowel disease — —Indication: acute pyogenic infection, fever of the unknown origo, osteomyelitis, prosthetic joint infection, vascular grafts infection… — —! MR is the method of the choice once there is a suspicion for spine osteomyelitis and no other underlying bone patology Radiolabeled leukocytes — Ant 4h Ant 24h Post 24h Post 4h Radiolabeled leukocytes — Post removal of OS, infection in soft tissues without osteomyelitis Respiratory system – nuclear imaging methods — —Perfusion study : 99mTc-MAA macroaggregated albumin- displays regional lung perfusion — —Ventilation study: radiolabeled aerosols (99mTc-DTPA), radioactive gases (81mKrypton) - display regional lung ventilation — — — — — —18F-FDG PET/CT, PET/MR : lung carcinoma, infection — Perfusion a ventilation scintigraphy —Indication: assess the probability of pulmonary embolism, assess regional lung perfusion before lung surgery (semiquantitative evaluation) — —Imaging: traditionally perfusion+ventilation (V/Q scan) - V/Q Mismatch —SPECT/low-doseCT perfusion only ¡Ventilation in uclear cases only — —Many centers performed both the perfusion and ventilation studies, clinical experience show that perfusion study by performing SPECT/CT is fully sufficient (depends on clinical context, technical equipment…) — —R-L shunt may be demostrated at images (activity is seen in the brain, kidneys) ‘Q’ comes from “quantité“, the French word for quantity or amount. French scientists like Darcy and Poiseuille derived equations involving rate of flow represented by the variable ‘Q’ Perfusion ventilation study PE 1.png Perfusion ventilation study SPECT perfuye ventilace plic.JPG Lung perfusion study, SPECT/CT — Lung perfusion study, SPECT/CT — Lung perfusion study, SPECT/CT — Thyroid imaging — —RP: 99mTcO4 (technetium pertechnetate), 123I, 131I —Planar images, SPECT, SPECT/CT — Thyroid scintigraphy - indication —Hyperthyroidism : autonomous/toxic adenoma, Graves disease, subacute thyreoiditis, compensatory low level TSH due to another disease — —Thyroid nodules : to determine their functional status — —Detection of the ectopic thyroid tissue, evaluation of the retrosternal tissue mass (retrosternal goiter, lingual thyroid, struma ovarii) — —Thyroid cancer (123I, 131I) staging — Therapy I 131 —Hospitalization required — —Malignant - patients with differentiated thyroid cancer: —Elimination of residues and micrometastases after TTE —Therapy of metastases found on follow up dg. scan with I131 — —Benign: —Autonomous adenoma —Relapse of autoimmune hyperthyroidism (Graves-Basedow) without endocrine orbitopathy Thyroid scintigraphy – normal finding — Thyroid scintigraphy – normal finding Tc štítnice.png —Cold nodule —Toxic adenoma studený uzel.png toxický uzel.png Thyroid study —Ectopic thyroid - substernal —Graves-Basedow disease GD.png Thyroid scintigraphy — —131I –normal finding —131I-dissemination I131.png I131 metastatické postižení.png Iodine 131 Parathyroid scintigraphy —Indication: preoperative localization of hyperfunctioning parathyroid glands making possible minimally invasive surgery —RP: 99mTc-MIBI – unspecific uptake in paratahyroid and thyroid gland — —Protocol: - -Two-phase scan (99mTc-MIBI), initial images 10 min after injection, second set of images at 2 hours, there is more rapid washout fromt the thyroid, so delayed images show hyperfunctioning parathyroid gland) - -Subtraction methodology (compares 99mTc-pertechnate study and 99mTc-MIBI study by digital subtraction) - —Planar images, but SPECT, SPECT/CT with better accuracy, localization of the parathyroid gland —If unclear/negative result – posibility of 18F-choline PET — MIBI normal finding MIBI PT norma.png MIBI - adenoma MIBI adenom.png MIBI adenoma MIBI adenom 2.png MIBI adenoma — Ant 2h Ant 5min MIBI adenoma — Ant 2h Ant 5min Central nervous system —Brain perfusion imaging -Epileptogenous focus, Brain death, evaluation of cerebrovascular reserve,, dementia (AD, vascular,…) - —Neuroreceptor imaging - DaTscan -Parkinson disease and syndromes, essential tremor, Dementia with Lewy Bodies - —(Cerebrospinal fluid imaging) -Evaluation of suspected CSF leaks, investigation of suspected communicating hydrocephalus (normal-pressure hydrocephalus), verification of CSF shunt patency — —PET : Amyloid imaging, 18F- FDG, 18-F-FLT…. — Brain perfusion —RP: 99mTc-HMPAO – lipophilic, crosses blood–brain barrier, enter neurons, becomes hydrophilic and is trapped — perfuze mozku 3.png Brain perfusion – epilepsy —Ictal Interictal farmakorezist. fokální epilepsie z levé pericentárlní oblasti, dle MR výrazná gyrifikace vlevo frontálně Brain death —Imaging methods for diagnosing brain death: Brain perfusion study, angiography, CT angiography, transcranial Doppler ultrasound — —Criteria for brain death (brain perfusion study): No intracerebral arterial, capillary or venous blood flow/tracer activity on the dynamic study, no visualisation of the sagittal sinus on immediate post-injected images (99mTc-HMPAO, 99mTc-ECD) — —Protocol: dynamic study, immediate post-injected images better in multiple projections, SPECT — —Advantages: No iodine contrast (possible nephrotoxic effect), simple intravenous injection, preferable in patients with lossy head injury or craniectomy (arteriography can be falsely negative) —Positive —Negative Brain death —Uptake is seen in the left hemisphere – negative study for the brain death —Total absence of cerebral uptake – brain death confirmed smrt negativní.png mozková smrt.png Brain death – 99mTc-HMPAO study Datscan – 123Ioflupan —Idiopatic Parkinson disease – degeneration of nigrostriatal pathways, impairment of afferent pathway from substantia nigra to BG = presynaptic impairment —Parkinson's disease plus diseases (MSA, PSP...) - directly affected striatum, affected pre- and postsynaptically —Essential tremor, parkinsonism secondary to medication = no dopamine synapse disorder — —123I-Ioflupan : distribution of presynaptic dopamine transporters, cocaine analogue, thyroid blockade preparation — —Indications: differentiation of Parkinson's disease and Parkinson plus diseases from essential tremor, dg. dementia with Lewy bodies https://www.mdpi.com/ijms/ijms-22-11234/article_deploy/html/images/ijms-22-11234-g001.png —Normal —Positive – Parkinson disease Datscan — — 99mTc-MIBI (sestamibi) —Nonspecific tumor binding agent, it is concentrated in mitochodria of the viable cells as a result of the passive difusion —Use: —cardiology (cardiac perfusion studies – dg. ICD) —endocrinology (localisation of hyperparathyroid gland) —oncology – follow up of patients with differentiated thyroid cancer as an alternative to 131I — - earlier in pts. with multiple myeloma, breast ca, soft tissue sarcomas — - accumulation also in other types of malignancies. — MIBI scan MIBI norma.png MIBI sarkom.png Normal finding: uptake in salivary glands, thyroid, myocardium, liver, colon , bladder, kidneys, small, intestinum , spleen, muscles Scintimammography breast cancer.png —- Adjunct procedure to mammography, ultrasound, MRI 123I-MIBG – adrenal medullary scintigraphy —Metajodobenzylguanidin = guanethidin analogue (similar to norepinephrin) that accumulates in adrenergic and neuroblastic tumors —Protocol: Wholebody planar scan + SPECT/CT at 4 and 24 hours after injection, patient preparation before study! (thyroid blockade) — —Indication : diagnosis, staging, management of adrenergic neuroectodermal tumors ( pheochromocytomas, extraadrenal paragangliomas, neuroblastomas), before planned 131I-MIBG therapy of medullary thyroid cancer — —Pheochromocytoma/paraganglioma – catecholamine-secreting tumors (hypertension, arrytmias), 10%bilateral pheochr., 10% extraadrenal paragangliomas, 10% malignant, found from the bladder up to the base of the skull —Neuroblastoma – embryonal malignancy of the sympathetic nervous system, typically in children younger than 4years of age, 70% originate in retroperitoneal area, 131I-MIBG for therapy after the failure of previous conventional therapies 123I-MIBG scan – normal finding MIBG norma 1.png —Prominent uptake in salivary glands, heart, liver —Colon and blader clearance —Mild uptake in nasal mucosa 123I-MIBG — Pheochromocytoma on 123I-MIBG scan feochromocytom.png —The increased uptake corresponds to a enlarged left adrenal mass with central necrosis on CT Imaging of somatostatin receptors —Imaging of the distribution of somatostatin receptors, which are highly expressed in neuroendocrine tumors (especially pulmonary and gastro-enteropancreatic NETs) — —111In-Pentetreotid (Octreoscan) - synthetic somatostatin analogue with high affinity to SSTR2, SSTR5 — Protocol : wholebody scan + SPECT/CT at 4h, 24h (sometimes 48h) after injection —Newer alternative: —Tektrotyd = 99mTc-EDDA/HYNIC-TOC – at 1h and 4h — - better image quality than Octreoscan (energy of 99mTc), 1-day exam, lower radiaton dose, lower price — —Indication: evaluating neuroendocrine tumors, especially carcinoid , gastroenteropanctreatic tumors, small cell lung cancer, meningioma, variable affinity for medullary thyroid cancer, insulinoma —Limitation : false positive uptake in bening inflammmatory granulomatous disease (sarcoidosis, TBC, IBD...), in tumors expressing lack of appropriate receptor subtype — —PET alternatives: —68Ga-DOTA-TOC - best sensitivity and image quality, lower availability (68Ga), higher price —18F-FDG PET useful in poorly differentiated neuroendocrine tumors — —Therapy: 177Lu-DOTA-TATE – beta- radiation therapy in patients with progressing GEP NETs Octreoscan – normal finding Octreoscan norma.png —Prominent uptake in spleen, liver —Kidneys clearance Tektrotyde – NET in ileum + lymph nodes — Tektrotyd vs Octreoscan Carcinoid - octreoscan octreoscan carcinoid.png Lymfoscintigraphy of limbs —RF: 99mTc-nanocoloid, subcutaneus —Indication: lymphedema Lymphoscintigraphy – SLN detection —Small amount of radioactive active colloidal tracer is injected into the skin in proximity to tumor leasion to determine the SLU receiveing drainage and thus possibly metastasizing tumor cells — —SLN (sentinel lymph node) = the first lymph node (nodes) which is first on a direct lymphatic drainage pathway from a primary tumor site, and as such is the most likely the location of metastasis — —Identification and histopathological examination of the SLU (after surgical removal) allow us to predict a regional metastatic potential of that given tumor and thus to choose optimal therapy — —99mTc-nannocolloid — —Indication : malignant melanoma, breast cancer, cancer of the tonque, neck, head, vulva — —Contraindication: already known metastatic disease indicated fo systemic therapy, suspected altered lymphatic drainage due to the previous surgery procedure Breast cancer – detection of SLN — SLU imaging – patient with melanoma sentinelová uzlina.png —Tracer was injected around the leasion on the lower back and drained to 2 lymph nodes. They were marked superficially over the skin