RADIOPHARMACEUTICALS IN ENDOCRINE IMAGING
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1 IAEA Regional Training Course (AFRA) on the Role of uclear Medicine in Endocrine Disease and Infection/Inflammation RADIPHARMACEUTICALS I EDCRIE IMAGIG Giuliano Mariani Regional Center of uclear Medicine, University of Pisa Medical School, Pisa, Italy Pretoria, South Africa, Dec. 6-10, 2010 Radioiodide/ 99m Tc 4 - IS Thyroid cell a +- a +- 99m Tc - I - 4 Basocellular membrane blood Apical membrane 1
2 99m Tc-Sestamibi MIBI
3 99m Tc-Sestamibi 15 min 99m Tc-Sestamibi 2.5 hr 3
4 131 I-Methyl-nor-Cholesterol Developed for scintigraphic imaging of the adrenal glands (cortical component) in the early 1970 s. Cholesterol analog entering the synthetic pathways of steroid hormones. Relatively slow synthesis, involving late imaging times (up to 7 days). Mandatory use of 131 I, despite its poor imaging characteristics. 4
5 131 I-Methyl-nor-Cholesterol Upon i.v. administration, it is transported by plasma lipoproteins. Active transport into cells of the adrenal cortex. Inside the cells, it is estherified and thus becomes a metabolically inert molecule. Estherified 131 I-methyl-nor-cholesterol is therefore trapped inside cells of the adrenal cortex. 5
6 [*I]MIBG Developed for imaging cells of the chromaffin system in the late 1970 s. ATP-mediated uptake, and storing in secretory vesicles. Released by exocytosis in the synaptic space. Secretory vesicles abundant in several tissues with adrenergic innervation (including the myocardium). [*I]MIBG Radiolabeled MIBG released in the synaptic space does not bind to post-synaptic receptors. Radiolabeled MIBG is not degraded by enzymes that degrade catecholamines (CMT, MA). Employed for scintigraphic imaging of neural crest tumors (including pheochromocytoma). Relatively fast kinetics of uptake/accumulation allows labeling with 123 I (favourable imaging characteristics). Labeling with 131 I mostly reserved for therapy. ovel applications of [ 123 I]MIBG for imaging cardiac innervation. 6
7 Some of the Multiple Facets of a euroendocrine Tumor Cell [*I]MIBG 18 F-DPA [ 11 C]5-HTP *MoAb *SST *CCK *VIP [ 18 F]FDG eurotransmitters HC HC HC HC H H H H SH HS H CH 3 H H H H H H CH 3 H H 2 7
8 -terminal E SST 1-5 receptors Protein G Affinity (IC 50 ) of Somatostatin Analogs for Human Receptors SST 1-5 Reubi et al. Eur J ucl Med 2000 (and subsequent data) 8
9 Eur J ucl Med Mol Imaging. 2007; 34: [DTA 0,-Tyr 3 ]-octreotide HC H-D-Phe Cys Tyr D-Trp In Y HC CH Thr (ol) Cys Thr Lys 9
10 [DTA 0,-Tyr 3 ]-octreotide HC H-D-Phe Cys Tyr D-Trp 68 Ga HC CH Thr (ol) Cys Thr Lys SST Agonist or Antagonist? 10
11 Several Types of Peptide Receptors in euroendocrine Tumors Somatostatin receptors - SST 1 SST 5 Bombesin receptors - BB1 or neuromedin B (MB) - BB2 or GRP - BB3 CCK1 and CCK2 receptors VIP Receptors - VPAC1 - VPAC2 GLP-1 receptors 11
12 99m Tc-Depreotide Synthetic peptide originally developed as an SST analog for imaging neuroendocrine tumors. High affinity for SST 3 (preferentially expressed by small cell lung cancer). Employed for differential diagnosis of solitary pulmonary nodules (including SCLC). Uptake possibly linked to infiltration of tumors by lymphocytes expressing SST 3 receptors? 99m Tc-Depreotide Blum J et al. Chest 2000;117:
13 99m Tc-EDDA/HYIC-Thy 3 -ctreotide ( 99m Tc-EDDA/HYIC-C, or 99m Tc-HYIC-C) 13
14 The 68 Ge/ 68 Ga Generator 14
15 18 F-DPA Tyrosine is a precursor of dopamine via L-DPA. 18 F-DPA is converted to 18 F-Dopamine, which can be degraded by both MA and CMT. In addition to the study of dopaminergic function for, e.g., movement disorders, 18 F-DPA is also used for imaging of neuroendocrine tumors with high decarboxylase activity. Pre-synaptic Axon CMT 3--MD 3--MD CMT 3--MD DDC DPA Dopamine DPA MA DPA DDC Dopamine DPAC HVA DPAC CMT MA 3MT Dopamine CMT DAT 15
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