¿Murió o permanece con vida el Tecnecio 99m? Una panorámica de desarrollos recientes con énfasis en la imagen de perfusión del miocardio
Contenido principal del artículo
Resumen
En el trabajo se exponen razones para considerar que el SPECT, particularmente con radiofármacos de continuará teniendo un importante papel en medicina nuclear, no obstante los avances asociados a la incorporación de la tecnología PET. Las razones que se examinan son las siguientes. Se aprecia un mejoramiento de la tecnología SPECT con el desarrollo de nuevos sistemas de detección y las ventajas de la aparición de los sistemas híbridos SPECT/TAC, la mayor vida media de los principales radionúclidos SPECT como y en comparación con los radionúclidos PET, lo que posibilita su traslado a mayores distancias, la realización de estudios con radiofármacos con más de un radionúclido en el mismo paciente y la posibilidad de detectar lesiones de baja captación, favorecido por lo indicado de las vidas medias. Finalmente se examinan los principales núcleos base de formación de complejos de con distintos ligandos que aseguran la aparición de nuevos radiofármacos de interés. Se examinan las potenciales aplicaciones oncológicas y cardiológicas con énfasis en estas últimas. Se considera que la radiofarmacia del continuará jugando un importante papel en medicina nuclear.
Detalles del artículo
Cómo citar
Duatti, A. (1). ¿Murió o permanece con vida el Tecnecio 99m? Una panorámica de desarrollos recientes con énfasis en la imagen de perfusión del miocardio. Nucleus, (52). Recuperado a partir de http://nucleus.cubaenergia.cu/index.php/nucleus/article/view/571
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Ciencias Nucleares
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Citas
1. BOSCHI A, DUATTI A, UCCELLI L. Development of technetium-99m and rhenium-188 radiopharmaceuticals containing a terminal metal-nitrido multiple bond for diagnosis and therapy. Topics Curr. Chem. 2005; 252: 85-115.
2. DUATTI A, UCCELLI L. Technetium complexes and radiopharmaceuticals containing the TcN multiple bond. Trends Inorg. Chem. 1996; 4: 27-41.
3. PASQUALINI R, et. al. A new efficient method for the preparation of 99mTc-radiopharmaceuticals containing the TcN multiple bond. Appl. Radiat. Isot. 1992; 43(11): 1329-1333.
4. BOLZATI C, et. al. Geometrically controlled selective formation of nitrido technetium(V) asymmetrical heterocomplexes with bidentate ligands. J. Am. Chem. Soc. 2000; 122(8): 4510-4511.
5. REFOSCO F, et. al. Mixed-Ligand Tc- and Re-nitrido complexes for radiolabeling bioactive molecules. Recent Res. Devel. Inorganic Chem. 2000; 2: 89-98.
6. BOLZATI C, et. al. Chemistry of the strong electrophilic metal fragment [99Tc(N)(PXP)]2+ (PXP = diphosphine ligand). A novel tool for the selective labeling of small molecules. J. Am. Chem. Soc. 2002; 124(38): 11468-11479.
7. BOCHER M, et. al. A fast cardiac gamma camera with dynamic SPECT capabilities: design, system validation and future potential. Eur. J. Nucl. Med. Mol. Imaging. 2010; 37: 1887–1902.
8. HUTTON BF. New SPECT technology: potential and challenges. Eur. J. Nucl. Med. Mol. Imaging. 2010; 37: 1883–1886.
9. ALBERTO R, et. al. Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+. J. Am. Chem. Soc. 2001; 123: 3135.
10. ALBERTO R. Radiopharmaceuticals. In: Bioorganometallics. Weinheim: Wiley-VCH, 2006. p 97.
11. ALBERTO R, et. al. A Novel Organometallic Aqua Complex of Technetium for the Labeling of Biomolecules: Synthesis of [99mTc(OH2)3(CO)3]+ from [99mTcO4]- in Aqueous Solution and Its Reaction with a Bifunctional Ligand. J. Am. Chem. Soc. 1998; 120(31): 7987-7988.
12. LIU S. The role of coordination chemistry in the development of target-specific radiopharmaceuticals. Chem. Soc. Rev. 2004; 33(7): 445-61.
13. THOMPSON KH, ORVIG C. Metal complexes in medicinal chemistry: new vistas and challenges in drug design. Dalton Trans. 2006; 14(6): 761-4.
14. LA BELLA R, et. al. In vitro and in vivo evaluation of a Tc-99m(I)-labeled bombesin analogue for imaging of gastrin releasing peptide receptor-positive tumors. Nucl. Med. Biol. 2002; 29(5): 553-560.
15. VEERENDRA B, et. al. Synthesis, radiolabeling and in vitro GRP receptor targeting studies of (99m) Tc-Triaza-X-BBN[7-14]NH2 (X = serylserylserine, glycylglycylglycine, glycylserylglycine, or beta alanine). Synth. React. Inorg. Me. 2006; 36: 481-491.
16. SMITH CJ, et. al. Radiochemical investigations of gastrin-releasing peptide receptor-specific [Tc-99m(X)(CO)(3)-Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: Syntheses, radiolabeling, and in vitro/in vivo studies where Dpr=2,3-diaminopropionic acid and X = H2O or P(CH2OH)(3). Cancer Res. 2003; 63 (14): 4082-4088.
17. WAIBEL R, et. al. Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex. Nat. Biotechnol. 1999; 17(9): 897-901.
18. FERREIRA CL, et. al. Glucosamine Conjugates of Tricarbonylcyclopentadienyl Rhenium(I) and Technetium(I) Cores. Inorg. Chem. 2006; 45(17): 6979-6987.
19. FERREIRA, et. al. Carbohydrate-appended 3-hydroxy-4-pyridinone Complexes of the [M(CO)(3)](+) core (M) Re, Tc-99m, Re-186). Bioconjugate Chem. 2006; 17(5): 1321-1329.
20. SCHIBLI R, et. al. Synthesis and in vitro characterization of organometallic rhenium and technetium glucose complexes against glut 1 and hexokinase. Bioconjugate Chem. 2005; 16(1): 105-112.
21. BERNARD J, et. al. Aqueous Synthesis of Derivatized Cyclopentadienyl Complexes of Technetium and Rhenium Directed Toward Radiopharmaceutical Application. Inorg. Chem. 2003; 42(4): 1014-1022.
22. TZANOPOULOU S, et. al. Synthesis, Characterization, and Biological Evaluation of M(I)(CO)(3)(NNO) Complexes (M = Re, Tc-99m) Conjugated to 2-(4-aminophenyl)benzothiazole as Potential Breast Cancer Radiopharmaceuticals. J. Med. Chem. 2006; 49(18): 5408-10.
23. LIU Y, et. al. Amino Acids Labeled with [99mTc(CO)3]+ and Recognized by the L-Type Amino Acid Transporter LAT1. J. Am. Chem. Soc. 2006; 128(50): 15996-97.
24. STEPHENSON KA, et. al. Bridging the gap between in vitro and in vivo imaging: Isostructural Re and Tc-99m complexes for correlating fluorescence and radioimaging studies. J. Am. Chem. Soc. 2004; 126(29): 8598-99.
25. ALBERTO R. [Tc(CO)3]+ Chemistry: a Promising New Concept for SPET?. Eur. J. Nucl. Med. Mol. I. 2003; 30(9): 1299-1302.
26. WELCH M. [Tc(CO)3]+ chemistry: a promising new concept for SPET?. Eur. J. Nucl. Med. Mol. Imaging. 2003; 30(9): 1302-1304.
27. GARCIA R, PAULO A, DOMINGOS A, et. al. Re and Tc complexes containing B-H...M agostic interactions as building blocks for the design of radiopharmaceuticals. J. Am. Chem. Soc. 2000; 122(45): 11240-11241.
28. WALD J, et. al. Aqueous One-Pot Synthesis of Derivatized Cyclopentadienyl-Tricarbonyl Complexes of 99mTc with an In Situ CO Source: Application to a Serotonergic Receptor Ligand. Angew. Chem. Int. Ed. 2001; 40(16): 3062-3066.
29. ALBERTO R, et. al. Mono-, Bi-, or Tridentate Ligands? The Labeling of Peptides with Tc-99m-Carbonyls. Biopolymers. 2004; 76(4): 324-333.
30. PASQUALINI R, et. al. Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents. J. Nucl. Med. 1994; 35(2): 334-341.
31. PASQUALINI R, DUATTI A. Synthesis and characterization of the new neutral myocardial imaging agent [99mTcN(noet)2] (noet = N-ethyl-N-ethoxydithiocarbamato). J. Chem. Soc. Chem. Commun. 1992; (18): 1354-1355.
32. JOHNSON G, et. al. Clearance of technetium-99m N-NOEt in normal, ischemic-reperfused, and membrane-disrupted myocardium. J. Nucl. Cardiol. 1996; 3(1): 42-54.
33. GIGANTI M, et. al. Advances in radiopharmaceuticals for cardiac imaging: 99mTcN-NOET. Q. J. Nucl. Med. 1997; 41(Suppl.): 147-151.
34. TAKEHANA K, et. al. Assessment of residual coronary stenoses using 99mTc-N-NOET vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction. J. Nucl. Med. 2001; 42(9): 1388-1394.
35. VANZETTO G, et. al. 99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction. Circulation. 2000; 101(20): 2424-2430.
36. HOLLY TA, et. al. The effect of ischemic injury on the cardiac transport of Tc-99m-N-NOET in the isolated rabbit heart. J. Nucl. Cardiol. 1999; 6(6): 633-640.
37. VANZETTO G, et. al. Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow. Circulation. 1997; 96(7): 2325-2331.
38. JEETLEY P, et. al. Comparison between Tc-99m-N-NOET and Tl-201 in the assessment of patients with known or suspected coronary artery disease. J. Nucl. Cardiol. 2004; 11(6): 664-672.
39. PETRUZELLA FD, et. al. Optimal timing for initial and redistribution technetium-99m-N-NOET image acquisition. J. Nucl. Cardiol. 2000; 7(2): 123-131.
40. VANZETTO G, et. al. Biodistribution, dosimetry, and safety of myocardial perfusion imaging agent 99mTcN-NOET in healthy volunteers. J. Nucl. Med. 2000; 41(1): 141-148.
41. CALNON DA, et. al. Myocardial uptake of 99mTc-N-NOET and 201Tl during dobutamine infusion. Comparison with adenosine stress. Circulation. 1999; 100: 1653-1659.
42. JOHNSON G, et. al. Planar imaging of 99mTc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(V) can detect resting ischemia. J. Nucl. Cardiol. 1997; 4(3): 217-225.
43. SINUSAS AJ. Technetium 99m-N-NOET: although not equivalent to thallium-201, it still offers new opportunities. J. Nucl. Cardiol. 2000; 7(2): 185-188.
44. JOHNSON G, et. al. Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of myocardial redistribution. J. Nucl. Med. 1997; 38(1): 138-143.
45. JOHNSON G, et. al. Clearance of technetium 99mTcN-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium. J. Nucl. Cardiol. 1996; 3(1): 42-54.
46. UCCELLI L, et. al. Subcellular distribution of technetium-99mTcN-NOEt in rat myocardium. J.Nucl. Med. 1995; 36(11): 2075-2079.
47. BOSCHI A, et. al. Synthesis and biological evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties. J. Nucl. Med. 2003; 44(5): 806-814.
48. OSCHI A, BOLZATI C, UCCELLI L, et. al. A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties. Nucl. Med. Commun. 2002; 23(7): 689-693.
49. HATADA K, et. al. 99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats. J. Nucl. Med. 2004; 45(12): 2095-2101.
50. BOLZATI C, et. al. Subcellular distribution and metabolism studies of the potential myocardial imaging agent [99mTc(N)(DBODC)(PNP5)]+. J. Nucl. Med. 2008; 49(8): 1336-1344.
51. ZHANG WC, et. al. Experimental study of [99mTc(PNP5) (DBODC)]+ as a new myocardial perfusion imaging agent. Cardiology. 2009; 112(2): 89-97.
52. HATADA K, et. al. Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses. J. Nucl. Cardiol. 2006; 13(6): 779-790.
53. CITTANTI C, et. al. Whole-body biodistribution and radiation dosimetry of the new cardiac tracer 99mTc-N-DBODC. J. Nucl. Med. 2008; 49(8): 1299-1304.
54. KIM YS, et. al. Tc-99m-N-MPO: novel cationic Tc-99m radiotracer for myocardial perfusion imaging. J. Nucl. Cardiol. 2008; 15(4): 535-546.
55. KIM YS, et. al. Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: a new perfusion radiotracer for heart imaging. J. Nucl. Cardiol. 2009; 16(4): 571-579.
56. MARIA L, et. al. Tris(pyrazolyl)methane 99mTc tricarbonyl complexes for myocardial imaging. Dalton Trans. 2009; 28(4): 603-606.
57. MARIA L, et. al. Rhenium and technetium tricarbonyl complexes anchored by pyrazole-based tripods: novel lead structures for the design of myocardial imaging agents. Dalton Trans. 2007; 28(28): 3010–3019.
58. BLUM JE, HANDMAKER H, RINNE N A. The utility of a somatostatin-type receptor binding peptide radiopharmaceutical (P829) in the evaluation of solitary pulmonary nodules. Chest 1999; 115(1): 224-232.
59. CYR JE, et. al. Somatostatin receptor-binding peptides suitable for tumor radiotherapy with Re-188 or Re-186. Chemistry and initial biological studies. J. Med. Chem. 2007; 50 (6): 1354-1364.
60. DECRISTOFORO C, et. al. 99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide. J. Nucl. Med. 2000; 41(6): 1114-1119.
61. DECRISTOFORO C, et. al. 99mTc-EDDA/HYNIC-TOC- A new technetium-99m labelled radiopharmaceutical for imaging somatostatin receptor positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives. Eur. J. Nucl. Med. 2000; 27(9): 1318-1325.
62. GABRIEL M, et. al. An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. J. Nucl. Med. 2003; 44(5): 708-716.
63. FOLKMAN J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol. 2002; 29(6 Suppl. 6): 15-18.
64. HWANG R, VARNER J. The role of integrins in tumor angiogenesis. Hematol. Oncol. Clin. North. Am. 2004; 18(5): 991-1006.
65. LIU S, ROBINSON SP, EDWARDS DS. Radiolabeled integrin avb3 antagonists as radiopharmaceuticals for tumor radiotherapy. Topics Curr. Chem. 2005; 252: 193-216.
66. LIU S. 99mTc-Labeling of a hydrazinonicotinamide-conjugated vitronectin receptor antagonist useful for imaging tumors. Bioconjug. Chem. 2001; 12(4): 624-629.
67. LIU S, et. al. Effect of coligands on biodistribution characteristics of ternary ligand 99mTc complexes of a HYNIC-conjugated cyclic RGDfK dimer. Bioconjug. Chem. 2005; 16(6): 1580-1588.
68. LIU S, et. al. Evaluation of a 99mTc-labeled cyclic RGD tetramer for non-invasive imaging integrin avb3-positive breast cancer. Bioconjug. Chem. 2007; 18(2): 438-446.
69. LIU S, et. al. Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer. Bioconjug. Chem. 2006; 17(6): 1499-1507.
70. DECRISTOFORO C, et. al. [99mTc]HYNIC-RGD for imaging integrin avb3 expression, Nucl. Med. Biol. 2006; 33: 945-952.
2. DUATTI A, UCCELLI L. Technetium complexes and radiopharmaceuticals containing the TcN multiple bond. Trends Inorg. Chem. 1996; 4: 27-41.
3. PASQUALINI R, et. al. A new efficient method for the preparation of 99mTc-radiopharmaceuticals containing the TcN multiple bond. Appl. Radiat. Isot. 1992; 43(11): 1329-1333.
4. BOLZATI C, et. al. Geometrically controlled selective formation of nitrido technetium(V) asymmetrical heterocomplexes with bidentate ligands. J. Am. Chem. Soc. 2000; 122(8): 4510-4511.
5. REFOSCO F, et. al. Mixed-Ligand Tc- and Re-nitrido complexes for radiolabeling bioactive molecules. Recent Res. Devel. Inorganic Chem. 2000; 2: 89-98.
6. BOLZATI C, et. al. Chemistry of the strong electrophilic metal fragment [99Tc(N)(PXP)]2+ (PXP = diphosphine ligand). A novel tool for the selective labeling of small molecules. J. Am. Chem. Soc. 2002; 124(38): 11468-11479.
7. BOCHER M, et. al. A fast cardiac gamma camera with dynamic SPECT capabilities: design, system validation and future potential. Eur. J. Nucl. Med. Mol. Imaging. 2010; 37: 1887–1902.
8. HUTTON BF. New SPECT technology: potential and challenges. Eur. J. Nucl. Med. Mol. Imaging. 2010; 37: 1883–1886.
9. ALBERTO R, et. al. Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+. J. Am. Chem. Soc. 2001; 123: 3135.
10. ALBERTO R. Radiopharmaceuticals. In: Bioorganometallics. Weinheim: Wiley-VCH, 2006. p 97.
11. ALBERTO R, et. al. A Novel Organometallic Aqua Complex of Technetium for the Labeling of Biomolecules: Synthesis of [99mTc(OH2)3(CO)3]+ from [99mTcO4]- in Aqueous Solution and Its Reaction with a Bifunctional Ligand. J. Am. Chem. Soc. 1998; 120(31): 7987-7988.
12. LIU S. The role of coordination chemistry in the development of target-specific radiopharmaceuticals. Chem. Soc. Rev. 2004; 33(7): 445-61.
13. THOMPSON KH, ORVIG C. Metal complexes in medicinal chemistry: new vistas and challenges in drug design. Dalton Trans. 2006; 14(6): 761-4.
14. LA BELLA R, et. al. In vitro and in vivo evaluation of a Tc-99m(I)-labeled bombesin analogue for imaging of gastrin releasing peptide receptor-positive tumors. Nucl. Med. Biol. 2002; 29(5): 553-560.
15. VEERENDRA B, et. al. Synthesis, radiolabeling and in vitro GRP receptor targeting studies of (99m) Tc-Triaza-X-BBN[7-14]NH2 (X = serylserylserine, glycylglycylglycine, glycylserylglycine, or beta alanine). Synth. React. Inorg. Me. 2006; 36: 481-491.
16. SMITH CJ, et. al. Radiochemical investigations of gastrin-releasing peptide receptor-specific [Tc-99m(X)(CO)(3)-Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: Syntheses, radiolabeling, and in vitro/in vivo studies where Dpr=2,3-diaminopropionic acid and X = H2O or P(CH2OH)(3). Cancer Res. 2003; 63 (14): 4082-4088.
17. WAIBEL R, et. al. Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex. Nat. Biotechnol. 1999; 17(9): 897-901.
18. FERREIRA CL, et. al. Glucosamine Conjugates of Tricarbonylcyclopentadienyl Rhenium(I) and Technetium(I) Cores. Inorg. Chem. 2006; 45(17): 6979-6987.
19. FERREIRA, et. al. Carbohydrate-appended 3-hydroxy-4-pyridinone Complexes of the [M(CO)(3)](+) core (M) Re, Tc-99m, Re-186). Bioconjugate Chem. 2006; 17(5): 1321-1329.
20. SCHIBLI R, et. al. Synthesis and in vitro characterization of organometallic rhenium and technetium glucose complexes against glut 1 and hexokinase. Bioconjugate Chem. 2005; 16(1): 105-112.
21. BERNARD J, et. al. Aqueous Synthesis of Derivatized Cyclopentadienyl Complexes of Technetium and Rhenium Directed Toward Radiopharmaceutical Application. Inorg. Chem. 2003; 42(4): 1014-1022.
22. TZANOPOULOU S, et. al. Synthesis, Characterization, and Biological Evaluation of M(I)(CO)(3)(NNO) Complexes (M = Re, Tc-99m) Conjugated to 2-(4-aminophenyl)benzothiazole as Potential Breast Cancer Radiopharmaceuticals. J. Med. Chem. 2006; 49(18): 5408-10.
23. LIU Y, et. al. Amino Acids Labeled with [99mTc(CO)3]+ and Recognized by the L-Type Amino Acid Transporter LAT1. J. Am. Chem. Soc. 2006; 128(50): 15996-97.
24. STEPHENSON KA, et. al. Bridging the gap between in vitro and in vivo imaging: Isostructural Re and Tc-99m complexes for correlating fluorescence and radioimaging studies. J. Am. Chem. Soc. 2004; 126(29): 8598-99.
25. ALBERTO R. [Tc(CO)3]+ Chemistry: a Promising New Concept for SPET?. Eur. J. Nucl. Med. Mol. I. 2003; 30(9): 1299-1302.
26. WELCH M. [Tc(CO)3]+ chemistry: a promising new concept for SPET?. Eur. J. Nucl. Med. Mol. Imaging. 2003; 30(9): 1302-1304.
27. GARCIA R, PAULO A, DOMINGOS A, et. al. Re and Tc complexes containing B-H...M agostic interactions as building blocks for the design of radiopharmaceuticals. J. Am. Chem. Soc. 2000; 122(45): 11240-11241.
28. WALD J, et. al. Aqueous One-Pot Synthesis of Derivatized Cyclopentadienyl-Tricarbonyl Complexes of 99mTc with an In Situ CO Source: Application to a Serotonergic Receptor Ligand. Angew. Chem. Int. Ed. 2001; 40(16): 3062-3066.
29. ALBERTO R, et. al. Mono-, Bi-, or Tridentate Ligands? The Labeling of Peptides with Tc-99m-Carbonyls. Biopolymers. 2004; 76(4): 324-333.
30. PASQUALINI R, et. al. Bis(dithiocarbamato) nitrido technetium-99m radiopharmaceuticals: a class of neutral myocardial imaging agents. J. Nucl. Med. 1994; 35(2): 334-341.
31. PASQUALINI R, DUATTI A. Synthesis and characterization of the new neutral myocardial imaging agent [99mTcN(noet)2] (noet = N-ethyl-N-ethoxydithiocarbamato). J. Chem. Soc. Chem. Commun. 1992; (18): 1354-1355.
32. JOHNSON G, et. al. Clearance of technetium-99m N-NOEt in normal, ischemic-reperfused, and membrane-disrupted myocardium. J. Nucl. Cardiol. 1996; 3(1): 42-54.
33. GIGANTI M, et. al. Advances in radiopharmaceuticals for cardiac imaging: 99mTcN-NOET. Q. J. Nucl. Med. 1997; 41(Suppl.): 147-151.
34. TAKEHANA K, et. al. Assessment of residual coronary stenoses using 99mTc-N-NOET vasodilator stress imaging to evaluate coronary flow reserve early after coronary reperfusion in a canine model of subendocardial infarction. J. Nucl. Med. 2001; 42(9): 1388-1394.
35. VANZETTO G, et. al. 99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction. Circulation. 2000; 101(20): 2424-2430.
36. HOLLY TA, et. al. The effect of ischemic injury on the cardiac transport of Tc-99m-N-NOET in the isolated rabbit heart. J. Nucl. Cardiol. 1999; 6(6): 633-640.
37. VANZETTO G, et. al. Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow. Circulation. 1997; 96(7): 2325-2331.
38. JEETLEY P, et. al. Comparison between Tc-99m-N-NOET and Tl-201 in the assessment of patients with known or suspected coronary artery disease. J. Nucl. Cardiol. 2004; 11(6): 664-672.
39. PETRUZELLA FD, et. al. Optimal timing for initial and redistribution technetium-99m-N-NOET image acquisition. J. Nucl. Cardiol. 2000; 7(2): 123-131.
40. VANZETTO G, et. al. Biodistribution, dosimetry, and safety of myocardial perfusion imaging agent 99mTcN-NOET in healthy volunteers. J. Nucl. Med. 2000; 41(1): 141-148.
41. CALNON DA, et. al. Myocardial uptake of 99mTc-N-NOET and 201Tl during dobutamine infusion. Comparison with adenosine stress. Circulation. 1999; 100: 1653-1659.
42. JOHNSON G, et. al. Planar imaging of 99mTc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(V) can detect resting ischemia. J. Nucl. Cardiol. 1997; 4(3): 217-225.
43. SINUSAS AJ. Technetium 99m-N-NOET: although not equivalent to thallium-201, it still offers new opportunities. J. Nucl. Cardiol. 2000; 7(2): 185-188.
44. JOHNSON G, et. al. Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of myocardial redistribution. J. Nucl. Med. 1997; 38(1): 138-143.
45. JOHNSON G, et. al. Clearance of technetium 99mTcN-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium. J. Nucl. Cardiol. 1996; 3(1): 42-54.
46. UCCELLI L, et. al. Subcellular distribution of technetium-99mTcN-NOEt in rat myocardium. J.Nucl. Med. 1995; 36(11): 2075-2079.
47. BOSCHI A, et. al. Synthesis and biological evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties. J. Nucl. Med. 2003; 44(5): 806-814.
48. OSCHI A, BOLZATI C, UCCELLI L, et. al. A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties. Nucl. Med. Commun. 2002; 23(7): 689-693.
49. HATADA K, et. al. 99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats. J. Nucl. Med. 2004; 45(12): 2095-2101.
50. BOLZATI C, et. al. Subcellular distribution and metabolism studies of the potential myocardial imaging agent [99mTc(N)(DBODC)(PNP5)]+. J. Nucl. Med. 2008; 49(8): 1336-1344.
51. ZHANG WC, et. al. Experimental study of [99mTc(PNP5) (DBODC)]+ as a new myocardial perfusion imaging agent. Cardiology. 2009; 112(2): 89-97.
52. HATADA K, et. al. Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses. J. Nucl. Cardiol. 2006; 13(6): 779-790.
53. CITTANTI C, et. al. Whole-body biodistribution and radiation dosimetry of the new cardiac tracer 99mTc-N-DBODC. J. Nucl. Med. 2008; 49(8): 1299-1304.
54. KIM YS, et. al. Tc-99m-N-MPO: novel cationic Tc-99m radiotracer for myocardial perfusion imaging. J. Nucl. Cardiol. 2008; 15(4): 535-546.
55. KIM YS, et. al. Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: a new perfusion radiotracer for heart imaging. J. Nucl. Cardiol. 2009; 16(4): 571-579.
56. MARIA L, et. al. Tris(pyrazolyl)methane 99mTc tricarbonyl complexes for myocardial imaging. Dalton Trans. 2009; 28(4): 603-606.
57. MARIA L, et. al. Rhenium and technetium tricarbonyl complexes anchored by pyrazole-based tripods: novel lead structures for the design of myocardial imaging agents. Dalton Trans. 2007; 28(28): 3010–3019.
58. BLUM JE, HANDMAKER H, RINNE N A. The utility of a somatostatin-type receptor binding peptide radiopharmaceutical (P829) in the evaluation of solitary pulmonary nodules. Chest 1999; 115(1): 224-232.
59. CYR JE, et. al. Somatostatin receptor-binding peptides suitable for tumor radiotherapy with Re-188 or Re-186. Chemistry and initial biological studies. J. Med. Chem. 2007; 50 (6): 1354-1364.
60. DECRISTOFORO C, et. al. 99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide. J. Nucl. Med. 2000; 41(6): 1114-1119.
61. DECRISTOFORO C, et. al. 99mTc-EDDA/HYNIC-TOC- A new technetium-99m labelled radiopharmaceutical for imaging somatostatin receptor positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives. Eur. J. Nucl. Med. 2000; 27(9): 1318-1325.
62. GABRIEL M, et. al. An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. J. Nucl. Med. 2003; 44(5): 708-716.
63. FOLKMAN J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol. 2002; 29(6 Suppl. 6): 15-18.
64. HWANG R, VARNER J. The role of integrins in tumor angiogenesis. Hematol. Oncol. Clin. North. Am. 2004; 18(5): 991-1006.
65. LIU S, ROBINSON SP, EDWARDS DS. Radiolabeled integrin avb3 antagonists as radiopharmaceuticals for tumor radiotherapy. Topics Curr. Chem. 2005; 252: 193-216.
66. LIU S. 99mTc-Labeling of a hydrazinonicotinamide-conjugated vitronectin receptor antagonist useful for imaging tumors. Bioconjug. Chem. 2001; 12(4): 624-629.
67. LIU S, et. al. Effect of coligands on biodistribution characteristics of ternary ligand 99mTc complexes of a HYNIC-conjugated cyclic RGDfK dimer. Bioconjug. Chem. 2005; 16(6): 1580-1588.
68. LIU S, et. al. Evaluation of a 99mTc-labeled cyclic RGD tetramer for non-invasive imaging integrin avb3-positive breast cancer. Bioconjug. Chem. 2007; 18(2): 438-446.
69. LIU S, et. al. Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer. Bioconjug. Chem. 2006; 17(6): 1499-1507.
70. DECRISTOFORO C, et. al. [99mTc]HYNIC-RGD for imaging integrin avb3 expression, Nucl. Med. Biol. 2006; 33: 945-952.