Padmakar Kulkarni

Iodine-123 phenylpentadecanoic acid: detection of acute myocardial infarction and injury in dogs using an iodinated fatty acid and single-photon emission tomography

The ability of an iodinated fatty acid, iodine-123 phenylpentadecanoic acid (1-123 PPA), and single-photon emission computed tomography (SPECT) to detect myocardium injured by temporary or permanent coronary arterial occlusion was evaluated. In 5 control dogs, 11 dogs that underwent 90 to 120 minutes of fixed left anterior descending coronary artery (LAD) occlusion, and 8 dogs that underwent 90 minutes of temporary LAD occlusion and up to 90 minutes of reflow, 2 to 6 mCi of I-123 PPA were injected and the dogs were imaged with SPECT. Control dogs showed relatively uniform uptake and clearance of I-123 PPA in similar left ventricular (LV) regions. Dogs with permanent LAD occlusion were identified by computer algorithm as having regions of decreased I-123 PPA uptake in the infarct-related area and a reduced rate of I-123 PPA clearance (-9.4% in infarct sectors [washin], +3.7% in sectors adjacent to the area of infarction, and +15.4% in control LV sectors [p less than 0.01]). Dogs with temporary LAD occlusion and reperfusion had decreased clearance of I-123 PPA from the regions with infarction; I-123 PPA clearance was -5.2 +/- 16.4% in infarct sectors, 12.7 +/- 7.4% in periinfarct zones, and 30.4 +/- 12% in control LV regions. These data demonstrate that tomographic analysis of I-123 PPA uptake and clearance permits the relatively noninvasive detection of LV myocardium injured by permanent or temporary LAD occlusion and reperfusion.

Identification and characterization of angiotensin II receptors in cardiac sarcolemma

Abstract We have used [125I] angiotensin II to investigate the presence of specific angiotensin II receptors in beef heart sarcolemmal membranes. The observed binding is saturable, reversible and specific. The apparent equilibrium dissociation constant is 2.23 ± 0.15 ( x ± SEM) and the maximal number of binding sites per mg membrane protein is 32.8 ± 5.4 fmol ( x ± SEM). The specific binding is 80–100% of the total [125I] angiotensin II bound and is directly proportional to membrane protein concentration over the range of 33–173 μg protein per ml. Angiotensin II and its antagonists competed for binding in a potency order of (agent, Ki): angiotensin II, 0.9nM > Sar1 Ala3, 7 nM > Sar1-Ile3, 51 nM > Sar1-Leu3, 427nM > angiotensin I, 1709 nM. The ability to characterize and quantify these receptors should now provide a method for investigating the mechanisms underlying the effects of angiotensin II on myocardial tissues.

19F LABELLED DEXTRANS AND ANTIBODIES AS NMR IMAGING AND SPECTROSCOPY AGENTS

19 F labelled compounds are disclosed which are useful in methods of NMR imaging and spectroscopy. The compounds comprise a 19 F-containing sensor moiety, and a transport polymer or substrate, and can optionally also comprise a spacer moiety to separate the sensor moiety and the transport polymer.

I-123 Labeled Radiotracers in Cardiovascular Nuclear Medicine

Radiohalogens (particularly 18F, 34mCl, 77Br, 75Br, 123I, 125I and 211At) produced in a cyclotron are nuclides of choice for radiopharmaceuticals. It has long been recognized that I-123 is the most desirable radioisotope of iodine for in vivo applications. I-123 labeled substrates suitable for imaging the myocardium include receptor binding agents, muscarinic antagonists and analogs of fatty acids. Radioiodinated (I-123) fatty acid analogs have gained significiant attention because of the possibility that these might give quantitative information regarding the regional myocardial metabolic activity by noninvasive scintigraphic methods. Incorporation of tellurium hetero into a carbon skeleton or beta methylation of a long chain phenyl fatty acid tends to prolong the retention of radioactivity in the myocardium of experimental animals. It is recognized that the radioiodine needs to be placed on a phenyl ring attached (in the ¿-position) to a long chain fatty acid for the in vivo stabilityof the C-I-bond. Among the methods of radioiodination of ¿-phenyl fatty acids, a method developed in our laboratory using an organo-thallium intermediate has been found to be simple, efficient, reproducible, and suitable for routine application.

Reconstruction Algorithm with Resolution Deconvolution in a Small-Animal PET Imager

A small-animal PET imaging device has been developed at the University of Texas Southwestern Medical Center at Dallas using scintillating 1-mm round BCF10 fibers and small admixture of CsF microcrystals between the fibers [Antich, 1990, Atac, 1991, Fernando, 1996 ]. The fiber core is polystyrene (C 8 H 8 )n doped with butyl-PBD and dPOPOP. The fibers are clad in a non-scintillating lucite cladding. The scintillation mechanism can be either from the excitation of π electrons in the butyl-PBD benzene ring in the fiber or from excitation within the microcrystals. In both cases, the emitted light is compatible with the optimal spectral response of standard photomultiplier cathodes. For a 511 keV photon in plastic,the photo-absorption is small, and Compton scatter interactions are dominant. The scattered electrons give up their energy well within a fiber diameter, but wave-shifting produces light in proximal fibers. The current imager uses the 2-fold coincident detection of a single event in 2 orthogonal fibers of 1-mm diameter to detect the location and the energy transferred at a point within the detector. Two sets of fibers each 60 cm in length and 1 mm in diameter were used to construct two alternating, mutually orthogonal sets of 14 planar arrays of 135 fibers each. In this detector, the planar fiber arrays are arranged along two alternating mutually orthogonal (X and Y)axes and are stacked along a third (Z). Scintillating light from the fibers is detected by two (X and Y directions) Hamamatsu R-2486 Position Sensitive Photomultiplier Tubes (PSPMT). A single-ended readout scheme is used, where the X,Z and Y,Z interaction positions in a detector are determined from coincident detection in the two PSPMT. The precision of the detection of the interaction point depends upon PSPMT performance and software filters.

Iodine-123 Phenylpentadecanoic Acid: Detection of Acute Myocardial Infarction in Anesthetized Dogs

Long-chain fatty acids are the preferred substrate of cardiac muscle. Therefore, radiolabeled free fatty acids are a natural choice for the non- invasive evaluation of myocardial metabolism and extensive research has focused on the development of radiolabeled free fatty acids for myocardial imaging (1–5). Evans et al. in 1965 successfully radioiodinated (I–131) oleic acid across a double bond and produced crude images of the myocardium in dogs, thus demonstrating the potential of radiolabeled free fatty acids for external, noninvasive myocardial imaging (1). Subsequently, heptadecanoic acid and hexadecanoic acid have been studied extensively in experimental animals and have shown promise in preliminary clinical assessments (2–5). However, for myocardial imaging, the terminally iodinated straight-chain free-fatty acids have two major problems, including (a) they are metabolized rapidly by the myocardium and (b) significant blood pool radioactivity results from free iodide released along with beta oxidation of the fatty acid in the myocardium and liver.

Iterative Image Processing for Early Diagnostic of Beta-Amyloid Plaque Deposition in Pre-Clinical Alzheimer’s Disease Studies

PURPOSEnTo test and evaluate an efficient iterative image processing strategy to improve the quality of sub-optimal pre-clinical PET images. A novel iterative resolution subsets-based method to reduce noise and enhance resolution (RSEMD) has been demonstrated on examples of PET imaging studies of Alzheimers disease (AD) plaques deposition in mice brains.nnnMATERIALS AND METHODSnThe RSEMD method was applied to imaging studies of non-invasive detection of beta-amyloid plaque in transgenic mouse models of AD. Data acquisition utilized a Siemens Inveon® micro PET/CT device. Quantitative uptake of the tracer in control and AD mice brains was determined by counting the extent of plaque deposition by histological staining. The pre-clinical imaging software inviCRO® was used for fitting the recovery PET images to the mouse brain atlas and obtaining the time activity curves (TAC) from different brain areas.nnnRESULTSnIn all of the AD studies the post-processed images proved to have higher resolution and lower noise as compared with images reconstructed by conventional OSEM method. In general, the values of SNR reached a plateau at around 10 iterations with an improvement factor of about 2 over sub-optimal PET brain images.nnnCONCLUSIONSnA rapidly converging, iterative deconvolution image processing algorithm with a resolution subsets-based approach RSEMD has been used for quantitative studies of changes in Alzheimers pathology over time. The RSEMD method can be applied to sub-optimal clinical PET brain images to improve image quality to diagnostically acceptable levels and will be crucial in order to facilitate diagnosis of AD progression at the earliest stages.