Tracer of myocardial

T.R. de Grade, S. Wang, J.E. Holden, R.J. Mickles, M. Taylor, C.K. Stone, Synthesis and preliminary evaluation of [ F]-labelled 4-thia palmitate a pet tracer of myocardial fatty acid oxidation, Nucl. Med. Biol. 27 (2000) 221-231. 

R.D. Timothy, C.M. Detlef, Non-/t-oxidizable tu-[ F]-fluoro long chain fatty acid analogues show cytochrome P-450 mediated defluorination implication for the design of PET-tracers of myocardial fatty acid utilization, Nucl. Med. Biol. 19 (1992) 389-397. 

Since fatty acids are the primary substrate for aerobic metabolism within the heart, they are also of interest as potentially useful tracers of myocardial perfusion (12-18). This class of compounds labeled with the positron emitter is being used with specially designed positron imaging (ECT) systems to quantitatively measure the regional distribution of myocardial blood flow in three dimensions (12,13,14). Carbon-11 labeled palmitic acid is also being evaluated as a tracer for studies of myocardial metabolism. Likewise, the o-iodofatty acids, which are structural analogs of the physiologic substrates, have been shown to be taken up by myocardial tissue in proportion to blood flow (15). Iodine-123 labeled 16-iodo-9-hexadecenoic acid (18,17) and 17-iodo-heptadeca-noic acid (18) have been used in conjunction with conventional scintillation cameras for in vivo studies in humans. In all cases with this class of compounds, turnover of the label within the tissue is related to some aspect of metabolism (17,18). 

Ng CK, Sisanus AJ, Zaret BL, Soufer R. Kinetic analysis of technetium-99m-labeled nitroimidazole (BMS-181321) as a tracer of myocardial hypoxia. Circulation 1995 92 1261-1268. 

PET offers the possibility to quantitatively measure the myocardial blood flow (MBF). MBF tracers can be divided into two groups. The first group is freely diffusible and represented by [ 0]H20. These tracers do not show any specific absorption and their distribution is completely determined by diffusion. Consequently, the measurement of the MBF is based on the first-pass extraction and clearance data. Because of the low heart-to-blood radioactivity ratio, the freely diffusible tracers provide myocardial images with low signal-to-background ratios. The second class is composed of highly extractable heart tracers. The tracer p NjNHs belongs to this family. These radiolabeled compounds are characterized by a selective extraction and retention in the myocardium. The... 

T.R. DeGrado, M.T. Kitapci, S. Wang, J. Ying, G.D. Lopaschuk, Validation of F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation Effects of hypoxia and composition of exogenous fatty acids, J. Nucl. Med. 47 (2006) 173-181. T.M. Shoup, D.R. Elmaleh, A.A. Bonab, A.J. Fischman, Evaluation of trans-9- F-fluoro-3,4-methyleneheptadecanoic acid as a PET tracer for myocardial fatty acid imaging, J. Nucl. Med. 46 (2005) 297-304. 

The Rb-82 generator permits serial studies in the same patient as often as every 10 minutes with 20-60 mCi of Rb-82 for rapid bolus intravenous infusion. Inherent in the administration of high levels of Rb-82 activity is the need for precise flow control from an automated system to deliver the desired amount of radioactivity. The development of the alumina column parameters and the elution protocol as well as the automated microprocessor system controller are presented here. Some of the details of this system have been discussed in earlier publications (15,21). Generator produced Rb-82 is used as a diffusible flow tracer in myocardial perfusion studies and as a nondiffusible tracer in brain studies to assess blood brain barrier permeability changes in patients with brain tumors or Alzheimer s type dementia. 

Tracers used for assessment of myocardial metabolism are selected based on the type of metabolism of interest EDO traces glucose metabolism, ["Cjpalmitate traces mitochondrial fatty acid metabolism, and ["Cjacetate is an indirect marker for myocardial oxygen consumption, allowing assessment of ventricular performance. [ CjPalmitate is a useful marker for normal myocardial oxygen consumption because baseline energy needs of the myocardium... 

As a final point, it should be noted that amino acids themselves exhibit some myocardial specificity (71, 72,73) and, thus, the metabolic-ally generated labeled amino acids contribute to total heart uptake and further confuse the issue. One can readily see that this use of N-labeled ammonia as a tracer for myocardial metabolism presents a very complex situation in which determination of even relative metabolic rates is di Scult at best and absolute measurements become virtually impossible. 

An example of this type of ne>v agent may be found in the fluorinated fatty acids, >vhich have been shovm to be taken up by the myocardium (60,61). When these compounds are labeled with attached to an even-numbered carbon atom they are highly toxic because of their ability to be converted to fluorocitrate, which is a suicide inhibitor of aconitase (73). The label thus becomes locked into an intermediate step of the citric acid cycle. When is attached to an odd-numbered carbon, toxicity is dramatically reduced, and )8-oxidation and subsequent metabolism proceeds as with the physiologic FFA substrates. A more detailed understanding of the behavior of such tracer molecules in altered and normal states of myocardial metabolism may provide considerable insight into applying them to the in vivo measurement of metabolic rates. 

The biological behavior of myocardial imaging agents has excellently been reviewed in particular in respect of the mechanism of myocardial uptake, the relationship between myocardial blood flow and radiotracer uptake, and redistribution of the tracers (Jain 1999). 

Thallium acetate was once used medicinally as a topical depilatory and for treating venereal diseases such as syphilis or gonorrhea [7] (reviewed in [8]). Currently, the only medicinal use is the nonpharmacological use of ° T1 as a tracer in myocardial imaging. 

T. Takahashi, S. Nishimura, T. Ido, K. Ishiwata, R. Iwata, Biological evaluation of 5-methyl-branched-chain omega-[ F]-fluorofatty acid A potential myocardial imaging tracer for positron emission tomography, Nucl. Med. Biol. 23 (1996) 303-308. 

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