[en] This 2-day conference is designed to bring scientist working in nuclear medicine, as well as nuclear medicine practitioners together to discuss the advances in four selected areas of imaging: Biochemical Parameters using Small Animal Imaging, Developments in Small Animal PET Imaging, Cell Labeling, and Imaging Angiogenesis Using Multiple Modality. The presentations will be on molecular imaging applications at the forefront of research, up to date on the status of molecular imaging in nuclear medicine as well as in related imaging areas. Experts will discuss the basic science of imaging techniques, and scheduled participants will engage in an exciting program that emphasizes the current status of molecular imaging as well as the role of DOE funded research in this area

[en] Molecular imaging is becoming a larger part of imaging research and practice. The Office of Biological and Environmental Research of the Department of Energy funds a significant number of researchers in this area. The proposal is to partially fund a workshop to inform scientists working in nuclear medicine and nuclear medicine practitioners of the recent advances of molecular imaging in nuclear medicine as well as other imaging modalities. A limited number of topics related to radionuclide therapy will also be discussed. The proposal is to request partial funds for the workshop entitled ''Translational Applications of Molecular Imaging and Radionuclide Therapy'' to be held prior to the Society of Nuclear Medicine Annual Meeting in Toronto, Canada in June 2005. The meeting will be held on June 17-18. This will allow scientists interested in all aspects of nuclear medicine imaging to attend. The chair of the organizing group is Dr. Michael J. Welch. The organizing committee consists of Dr. Welch, Dr. William C. Eckelman and Dr. David Vera. The goal is to invite speakers to discuss the most recent advances of modern molecular imaging and therapy. Speakers will present advances made in in vivo tagging imaging assays, technical aspects of small animal imaging, in vivo imaging and bench to bedside translational study; and the role of a diagnostic scan on therapy selection. This latter topic will include discussions on therapy and new approaches to dosimetry. Several of these topics are those funded by the Department of Energy Office of Biological and Environmental Research

[en] [¹⁸F]Benperidol ([¹⁸F]BP), a positron-emitting analogue of the dopaminergic D₂ antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [¹⁸F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [¹⁸F]BP confirmed that the radioligand bound specifically to central D₂ receptors in vivo, and not to S₂ or D₁ receptors. [¹⁸F]BP bound to D₂ receptors in a reversible manner; unlabeled eticlopride displaced D₂ receptor-bound [¹⁸F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [¹⁸F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D₂ receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D₂ receptor sites

[en] ¹¹¹In-LDTPA galactose BSA (bovine serum albumin) was used to evaluate the asialoglycoprotein receptor (ASGPR) system in both normal and ASGPR-deficient mice. The radiolabeled glycoprotein had complete liver uptake in both normal and ASGPR-deficient mice. Metabolism and hepatic cell-type distribution studies were performed. The normal mouse excreted greater than 60% of the hepatic activity, while the ASGPR-deficient mouse excreted less than 40% of the hepatic activity. ¹¹¹In-LDTPA galactose BSA was metabolized to ¹¹¹In-LDTPA-L-lysine in both mouse types. Normal mice showed 70% of the radioactivity in the hepatocyte, whereas the homozygous ASGPR-deficient mouse had equal activity in the hepatocyte and the hepatic endothelial cell

[en] Cholesteryl-p-[¹⁸F]fluorobenzoate ([¹⁸F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [¹⁸F]CFB. The synthesis of [¹⁸F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [¹⁸F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [¹⁸F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [¹⁸F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [¹⁸F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [¹⁸F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [¹⁸F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders

[en] [¹¹C]Acetate, a myocardial PET imaging agent for analysis of oxidative metabolism, has potential use in tumor imaging. Aromatic fatty acids display antitumor effects with phenylacetate currently in clinical trial. Tumor differentiation and cytostasis resulting from phenylacetate treatment may involve the peroxisome proliferator-activated receptor alpha (PPARα). To examine whether aromatic fatty acids are potential imaging agents for PPARα or tumors in general, [¹¹C]phenylacetic acid (PAA) and [¹⁸F]fluorophenyl-acetic acid (FPAA) were synthesized and evaluated in EMT-6 tumor bearing mice and 9L-Glioma tumor bearing rats and compared to [¹¹C]acetate. [¹¹C]Acetate showed better tumor accumulation than PAA or FPAA. The aromatic fatty acids did not directly bind PPARα as confirmed by a biodistribution study of PAA in PPARα -/- mice

[en] Specific activity (SA), defined as the amount of radioactivity per unit mass of a compound, is arguably one of the most important parameters in radiopharmaceutical development, particularly in quality control of carbon-11- and fluorine-18-labeled compounds. This review article will outline the progression of improvements in SA over the last few decades. The International Symposium of Radiopharmaceutical Chemistry abstracts were an excellent source of materials for this review and will be referenced throughout.

[en] We have prepared two estrogens labeled with carbon-11, 17α-[¹¹C]methylestradiol and 11β-ethyl-17α-[¹¹C]methylestradiol, at a specific activity of 300-1000 Ci/mmol (11.1-37 TBq/mmol), and we have determined their in vivo biodistribution in immature female rats. Both compounds accumulated selectively in two target tissues, the uterus and ovaries, reaching levels of 3.5-4.9 %ID/g at 20 min and 4.6-6.6 %ID/g at 40 min; uterus-to-blood ratios reached 12-23. Uterine uptake showed a saturation dependence with the amount of injected mass, and was displaced by unlabeled estradiol, indicating that this uptake was receptor mediated. These results suggest that these compounds may be useful in estrogen receptor-based imaging of breast tumors

[en] We have synthesized and characterized four new fluorinated halobenzamides as sigma receptor ligands for use with positron emission tomography (PET). All the compounds were found to have high sigma-1 affinities (K_i = 0.38-0.98 nM), and the 4-fluoro-substituted benzamides were found to be more potent sigma-2 ligands (K_i = 3.77-4.02 nM) than their corresponding 2-fluoro analogs (K_i = 20.3-22.8 nM). The [¹⁸F] radiochemical syntheses of two of the analogs gave overall yields between 3-10% (EOS), radiochemical purities >99%, and specific activities between 800-1200 Ci/mmol (29.6-44.4 TBq/mmol). Rat biodistribution and blocking experiments were performed with 2-[¹⁸F](N-fluorobenzylpiperidin-4yl)-4-iodobenzamide, the analog with the best K_i value for sigma-1 sites (0.38 nM). Results of these experiments demonstrate specific uptake of the compound in tissues believed to contain sigma receptors, such as lungs, kidneys, heart, brain, and spleen and indicate its potential as a candidate for use in PET imaging of tissues containing these receptors

[en] Doisynolic acids, D-ring seco-steroids derived from alkaline fusion of estrones, are hormonal curiosities: Their binding affinity for the estrogen receptor is low (ca. 1-2% that of estradiol), but their in vivo potency is high and they have a long duration of action. To study the in vivo behavior of the doisynolic acids, we prepared fluorine-substituted analogs of both trans-doisynolic acid (with the natural 14α-hydrogen configuration, trans-FDA) and the more active cis-doisynolic acid (with the unnatural 14β-hydrogen configuration, cis-FDA) from estrone and 14β-estrone, respectively. Modification of the D-ring haloform cleavage approach of Meyers allowed us to introduce fluorine (or fluorine-18) on the carbon atom derived from C-16 in the estrones. Fluorine substitution had little effect on the estrogen receptor binding affinity of the doisynolic acids. Tissue distribution of the fluorodoisynolic acids (trans-[¹⁸F]FDA and cis-[¹⁸F]FDA) was unusual and very different from that of typical, high-affinity ligands for the estrogen receptor. At 1-3 h in immature female rats, trans-[¹⁸F]FDA shows low and rather nonselective uptake in the principal estrogen target tissue (uterus) and slow clearance. By contrast, cis-[¹⁸F]FDA shows high uptake in nearly all tissues, with significant uterine uptake that continues to increase over the 1-6-h period. The uterine uptake of this isomer was blocked at the later times by a sufficiently high dose of unlabeled cis-FDA. After administration of the trans-[¹⁸F]FDA, a more polar metabolite slowly accumulates in the blood. The cis-[¹⁸F]FDA, however, showed no apparent metabolism, with 84% of the blood activity at 5 h assigned as the unmetabolized radioligand. After 5 h, only limited clearance from blood, liver, and kidneys has occurred. No metabolite from this isomer accumulates in the uterus. Although fluorodoisynolic acids will not be useful breast-tumor imaging agents, their behavior was found to be interesting as it deviates from that of other F-18 estrogens. Further long-term studies of cis-doisynolic acid, labeled with tritium, may be needed to explicate fully its unusual distribution properties and high in vivo activity