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Michael J Welch

Publications and source records attributed to Michael J Welch.

At least 55 records · Page 3Linked to original sources
PubMed2005

Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury. PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults. A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis. Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions. The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development. The synthesis of [(11)C]PJ34 was accomplished by base-catalyzed reaction of the corresponding des-methyl precursor, N-(5,6-dihydro-6-oxophenanthridin-2-yl)-2-(methylamino)acetamide with [(11)C]methyl iodide in DMF. The radiolabeling yield was 60% and the specific activity was approximately 2000 mCi/micromol (decay corrected to E.O.B.). The total radiosynthesis time was approximately 50 min. Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated. These data indicate that [(11)C]PJ34 may be a useful radiotracer for imaging tissues undergoing cellular death via necrosis.

Animals↗
PubMed2005

Carbon-11 labeled sigma2 receptor ligands for imaging breast cancer.

Four conformationally flexible benzamide analogs having a high affinity and outstanding selectivity for sigma(2) versus sigma(1) receptors were synthesized and radiolabeled with carbon-11 by reaction with [(11)C]methyl iodide. The four (11)C-labeled radiotracers were evaluated for their potential to image the proliferative status of breast tumors with positron emission tomography (PET). In vivo studies in female BALB/C mice bearing EMT-6 breast tumors showed that one radiotracer, (2-methoxy-(11)C)-N-(4-(3,4-dihydro-6,7-dimethoxy-isoquinolin-2(1H)-yl)butyl)-5-methylbenzamide ([(11)C]2), had a high tumor uptake and suitable tumor/background ratio for imaging purposes. Blocking studies were consistent with the labeling of sigma(2) receptors in vivo. A study comparing the in vivo properties of [(11)C]2 and (18)F-3'-fluoro-3'-deoxy-L-thymidine ([(18)F]FLT) indicated that [(11)C]2 had either similar (lung, fat) or better (blood, muscle) tumor/organ ratios than [(18)F]FLT in the tissues that are important for breast tumor imaging. Consequently, [(11)C]2 is a potential radiotracer for imaging the proliferative status of breast tumors in vivo with PET.

Animals↗
PubMed2005

Cell line-dependent differences in uptake and retention of the hypoxia-selective nuclear imaging agent Cu-ATSM.

BACKGROUND: Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) [Cu-ATSM] is a potential marker for tumor hypoxia that has been under evaluation for clinical use. In this study, we examined the mechanisms underlying the uptake of (64)Cu in cells incubated with (64)Cu-ATSM. METHODS: The in vitro uptake of (64)Cu was determined as a function of oxygenation conditions and incubation time with (64)Cu-ATSM using four and two tumor cell lines of human origin and rodent origin, respectively. Additionally, the rate of (64)Cu efflux and Cu-ATSM metabolism was determined. RESULTS: (64)Cu accumulation is rapid during the first 0.5-1 h of incubation. It is highest in anoxic cells but is also significant in normoxic cells. After this initial period, the level of intracellular (64)Cu varies depending on the cell line and the oxygenation conditions and, in some circumstances, may decrease. During the first 0.5-1 h, the ratio of (64)Cu levels between anoxic and normoxic cells is approximately 2:10 and that between hypoxic (0.5% O(2)) and normoxic cells is approximately 1:2.5, depending on the cell line. These ratios generally decrease at longer times. The (64)Cu-ATSM compound was found to be metabolized during incubation in a manner dependent on oxygenation conditions. Within 2 h under anoxic conditions, (64)Cu-ATSM could no longer be detected, although 60-90% of the amount of (64)Cu added as (64)Cu-ATSM was present in the medium. Non-ATSM (64)Cu was taken up by the cells, albeit at a much slower rate. Efflux rates of (64)Cu were found to be cell line dependent and appeared to be inversely correlated with the final (64)Cu uptake levels under anoxic conditions. CONCLUSION: The uptake and retention of (64)Cu and their relation to oxygenation conditions were found to be cell line dependent. Given the complexities in the oxygen dependence and cell line-dependent kinetics of uptake and retention of Cu following exposure to Cu-ATSM, the clinical utility of this compound may be disease site specific.

Animals↗
PubMed2005

Techniques necessary for multiple tracer quantitative small-animal imaging studies.

INTRODUCTION: An increasing number and variety of studies on rodent models are being conducted using small-animal positron emission tomography scanners. We aimed to determine if animal handling techniques could be developed to perform routine animal imaging in a timely and efficient manner and with minimal effect on animal physiology. These techniques need to be reproducible in the same animal while maintaining hemodynamic and physiological stability. METHODS: The necessary techniques include (a) the use of inhalant anesthesia, (b) arterial and venous cannulation for multiple tracer administrations and blood sampling, (c) development of small-volume analytic columns and techniques and (d) measurement of the physiological environment during the imaging session. RESULTS: We provide an example of a cardiac imaging study using four radiotracers (15O-water, 1-[11C]-acetate, 1-[11C]-palmitate and 1-[11C]-glucose) injected into normal rats. Plasma substrates, CO2 production and total metabolites were measured. The animals remained anesthetized over the entire imaging session, and their physiological state was maintained. CONCLUSION: The intrastudy stability of the physiological measurements and substrate levels and interstudy reproducibility of the measurements are reported.

Animals↗
PubMed2005

Preparation of high specific activity (86)Y using a small biomedical cyclotron.

86Y is an attractive PET radionuclide due to its intermediate half-life. (86)Y was produced via the 86Sr(p,n)86Y nuclear reaction. Enriched SrCO3 or SrO was irradiated with 2-6 microA of beam current for <4 h on a CS-15 cyclotron. It was shown that the SrO target could withstand at least 6 microA of beam current, a significant improvement over a maximum of 2 microA on the SrCO3 target. Average yields of 4.5 mCi/microA.h were achieved with SrO, which represent 71% of the theoretical yield, compared to 2.3 mCi/microA.h with SrCO3. The radioisotopic contaminants were (86m)Y (220%), 87Y (0.27%), (87m)Y (0.43%) and 88Y (0.024%). 86Y was isolated in an electrochemical cell consisting of three Pt electrodes. The solution was electrolyzed at 2000 mA (40 min) using two Pt plate electrodes. A second electrolysis (230 mA for 20 min) was performed using one Pt plate and a Pt wire. On average, 97.1% of the 86Y was recollected on the Pt wire after a second electrolysis. The (86)Y was collected from the Pt wire using 2.8 M HNO3/EtOH (3:1). After evaporation, 86Y was reconstituted in 100 microl of 0.1 M HCl. Target materials were recovered as SrCO3 and then converted to SrO by thermal decomposition at 1150 degrees C. Specific activity of 86Y was determined to be 29+/-19 mCi/microg via titration of 86Y(OAc)3 with DOTA or DTPA. We have established techniques for the routine, economical production of high purity, high specific activity 86Y on a small biomedical cyclotron that are translatable to other institutions.

Biomedical Engineering↗
PubMed2005

Measurement of input functions in rodents: challenges and solutions.

INTRODUCTION: Tracer kinetic modeling used in conjunction with positron emission tomography (PET) is an excellent tool for the noninvasive quantification of physiological, biological and molecular processes and their alterations due to disease. Currently, complex multi-compartment modeling approaches are being applied in a variety of clinical studies to determine myocardial perfusion, viability and glucose utilization as well as fatty acid metabolism and oxidation in the normal and diseased heart. These kinetic models require two key measurements of tracer activity over time, tracer activity in arterial blood (input function) and its corresponding activity in the organ of interest. The alteration in the time course of tracer activity as it travels from blood to the organ of interest describes the kinetics of the tracer. To be able to implement these approaches in rodent models of disease using small-animal PET (microPET), it is imperative that the input function is measured accurately. METHODS: The blood input functions in rodent experiments were obtained by (1) direct blood sampling, (2) direct measurement of blood activity by a beta-detecting probe that counts the activity in the blood, (3) an arterial-venous bypass (A/V shunt), (4) factor analysis of dynamic structures from dynamic PET images and (5) measurement from region-of-interest (ROI) analysis of dynamic PET images. Direct blood sampling was used as the reference standard to which the results of the other techniques were compared. RESULTS: Beta probes are difficult to operate and may not provide accurate blood input functions unless they are used intravenously, which requires complicated microsurgery. A similar limitation applies to the A/V shunt. Factor analysis successfully extracts the blood input function for mice and rats. The ROI-based method is less accurate due to limited image resolution of the PET system, which results in severe partial volume effect and spillover from myocardium. CONCLUSION: The current reference standard, direct blood sampling, is more invasive and has limited temporal resolution. With current imaging technology, image-based extraction of blood input functions is possible by factor analysis, while forthcoming technological developments are likely to allow extraction of input function directly from the images. These techniques will reduce the level of complexity and invasiveness for animal experiments and are likely to be used more widely in the future.

Animals↗
PubMed2005

Positron-emitting isotopes produced on biomedical cyclotrons.

This review will discuss the production and applications of positron-emitting radionuclides for use in Positron Emission Tomography (PET), with emphasis on radionuclides that can be produced onsite with a biomedical cyclotron. In PET the traditional radionuclides of choice are (11)C, (113)N, (15)O and (18)F and although they will be briefly discussed in this article, the emphasis of this review will be on 'non-standard' PET radionuclides that are generating increased interest by the medical research community.

Animals↗
PubMed2005

Preparation, biodistribution, and small animal PET of 45Ti-transferrin.

UNLABELLED: Investigation of 45Ti-transferrin was pursued to provide insight into the mechanism of action of titanocene dichloride, a chemotherapeutic agent currently in clinical trials. METHODS: Plasma protein-binding studies of processed 45Ti were performed by solubilizing the 45Ti residue in 0.05N HCl, of which 1.22 MBq (33 microCi) in 10 microL were added to 250 microL of dog plasma. 45Ti-Transferrin was prepared by redissolving the processed 45Ti in 25 micromol/L apotransferrin or by in vivo incorporation through preparation and introduction of 45Ti-citrate. Biodistribution studies were performed on normal Sprague-Dawley rats and EMT-6 tumor-bearing BALB/c mice with 45Ti-transferrin coinjected with 67Ga-citrate for direct comparison. microPET was performed on mice bearing EMT-6 tumors and the images were analyzed for tumor-to-muscle uptake ratios. RESULTS: Direct labeling of apotransferrin in situ with 45Ti was achieved as well as in vivo incorporation by 2 h after injection with 45Ti-citrate. The biodistribution of 45Ti-transferrin and 67Ga-citrate showed similar trends. In Sprague-Dawley rats, initial blood uptake was higher for the 45Ti-transferrin, whereas bone uptake increased more for the 67Ga-citrate. EMT-6 tumor uptake in both cases was relatively high (14.6 +/- 1.83 %ID/g for 45Ti and 8.72 +/- 0.98 %ID/g for 67Ga [%ID/g = percentage injected dose per gram]) and remained elevated even out to 24 h after injection. The tumor-to-muscle ratio of the 67Ga-citrate reached 6.7 at 24 h, whereas the ratio of the 45Ti-transferrin increased to 4.3 at this time point. Uptake of 45Ti-transferrin was visualized in the EMT-6 murine mammary carcinoma tumor with microPET. In all cases, the tumor was clearly delineated from the surrounding tissue with tumor-to-muscle ratios on the order of 1.6. CONCLUSION: 45Ti forms a complex with apotransferrin that remains intact in vivo. Results of the biodistribution in mice showed that the tumor had increased uptake compared with nontarget organs (e.g., muscle). The microPET images of tumor-bearing mice clearly delineate the tumors from the surrounding tissue. Comparison of the data suggests that tissue uptake is similar whether injecting 45Ti-transferrin directly or as 45Ti-citrate, which transchelates to transferrin before the time of imaging.

Animals↗
PubMed2005

64Cu-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: synthesis, radiolabeling, and biologic evaluation.

UNLABELLED: Long-circulating nanoparticles functionalized with ligands for receptors overexpressed by tumor cells have promising applications for active and passive tumor targeting. The purpose of this study was to evaluate 64Cu-radiolabeled folate-conjugated shell cross-linked nanoparticles (SCKs) as candidate agents to shuttle radionuclides and drugs into tumors overexpressing the folate receptor (FR). METHODS: SCKs were obtained by cross-linking the shell of micelles obtained from amphiphilic diblock copolymers. SCKs were then functionalized with folate, fluorescein thiosemicarbazide (FTSC), and 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (TETA). The specific interaction of SCK-folate with the FR was investigated on KB cells. The biodistributions of 64Cu-TETA-SCK and 64Cu-TETA-SCK-folate were evaluated in athymic mice bearing small-size KB cell xenografts (10-100 mg), whereas the intratumor distributions were investigated by autoradiography in 0.3- to 0.6-g KB cell xenografts. RESULTS: A global solution-state functionalization strategy has been introduced for attaching optimum numbers of targeting and imaging agents onto the SCKs for increasing the efficiency of interaction with cell-surface receptors. Epifluorescence microscopy confirmed the specific interaction of FTSC-SCK-folate with the FR in vitro. 64Cu labeling of TETA-SCKs led to the radiolabeled compounds with 15%-20% yield and >95% radiochemical purity. The biodistribution results demonstrated high accumulation of 64Cu-labeled SCKs in organs of the reticuloendothelial system (RES) (56.0 +/- 7.1 %ID/g and 45.7 +/- 3.5 %ID/g [percentage injected dose per gram] in liver at 10 min after injection for folated and nonfolated SCKs, respectively) and a prolonged blood circulation. No increase of SCK tumor uptake deriving from folate conjugation was observed (5.9 +/- 2.8 %ID/g and 6.0 +/- 1.9 %ID/g at 4 h after injection for folated and nonfolated SCKs, respectively). However, tumor accumulation was higher in small-size tumors, where competitive block of SCK-folate uptake with excess folate was observed. Autoradiography results confirmed the extravasation of radiolabeled SCKs in vascularized areas of the tumor, whereas no diffusion was observed in necrotic regions. CONCLUSION: Despite high RES uptake, the evaluated 64Cu-labeled SCKs exhibited long circulation in blood and were able to passively accumulate in tumors. Furthermore, SCK-folate uptake was competitively blocked by excess folate in small-size solid tumors, suggesting interaction with the FR. For these reasons, functionalized SCKs are promising drug-delivery agents for imaging and therapy of early-stage solid tumors.

Animals↗
PubMed2004

Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy.

Evidence is emerging that systemic metabolic disturbances contribute to cardiac myocyte dysfunction and clinically apparent heart failure, independent of associated coronary artery disease. To test the hypothesis that perturbation of lipid homeostasis in cardiomyocytes contributes to cardiac dysfunction, we engineered transgenic mice with cardiac-specific overexpression of fatty acid transport protein 1 (FATP1) using the alpha-myosin heavy chain gene promoter. Two independent transgenic lines demonstrate 4-fold increased myocardial free fatty acid (FFA) uptake that is consistent with the known function of FATP1. Increased FFA uptake in this model likely contributes to early cardiomyocyte FFA accumulation (2-fold increased) and subsequent increased cardiac FFA metabolism (2-fold). By 3 months of age, transgenic mice have echocardiographic evidence of impaired left ventricular filling and biatrial enlargement, but preserved systolic function. Doppler tissue imaging and hemodynamic studies confirm that these mice have predominantly diastolic dysfunction. Furthermore, ambulatory ECG monitoring reveals prolonged QT(c) intervals, reflecting reductions in the densities of repolarizing, voltage-gated K+ currents in ventricular myocytes. Our results show that in the absence of systemic metabolic disturbances, such as diabetes or hyperlipidemia, perturbation of cardiomyocyte lipid homeostasis leads to cardiac dysfunction with pathophysiological findings similar to those in diabetic cardiomyopathy. Moreover, the MHC-FATP model supports a role for FATPs in FFA import into the heart in vivo.

Animals↗
PubMed2004

Comparative in vivo behavior studies of cyclen-based copper-64 complexes: regioselective synthesis, X-ray structure, radiochemistry, log P, and biodistribution.

The in vivo behavior of copper(II)-cyclen complexes was modified via substitution of the parent ligand with two different substituents, 4-tert-butylbenzyl and acetate. This was achieved by using same synthetic strategy (regioselective protection/first alkylation/deprotection/second alkylation) to give nine cyclen derivatives. The X-ray structure of [Cu(2c)Cl]+ (2c = 1-(4-tert-butylbenzyl)-1,4,7,10-tetraazacyclododecane) showed that the chlorine ion from the reaction mixture occupied the remaining apical position of a square pyramidal coordination environment of these Cu-cyclen complexes. Eight out of nine compounds were labeled with 64Cu in high radiochemical purity. log P measurements showed that the lipophilicities of the copper complexes were increased dramatically by attaching hydrophobic substituents on the nitrogen atoms of cyclen. Conversely, as the number of acetate groups increased, the lipophilicity was decreased. The biodistribution of Cu-cyclen complexes was found to be influenced mostly by the overall charge of the complexes rather than their lipophilicity. Positively charged (+2) complexes showed high blood retention at early time points with sluggish clearance from liver by 24 h. The attachment of even one acetate group onto cyclen accelerated blood and liver clearance dramatically compared to +2 charged Cu(II) complexes. Neutral trans-substituted Cu-4 showed the best clearance and lowest retention of doses from all organs most time, followed by -1 charged complex Cu-2. Trans-substituted complexes structure isomers Cu-3 and Cu-4 showed better clearance and lower retention from all organs than their cis-counterparts Cu-5 and Cu-6.

Animals↗
PubMed2004

Development and evaluation of a reference measurement procedure for the determination of total 3,3',5-triiodothyronine in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry.

3,3',5-Triiodothyronine (T3) is an important diagnostic marker for thyroid function. A reference measurement procedure (RMP) for total T3 in serum involving isotope dilution coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been developed and critically evaluated. The method uses solid-phase extraction with mixed-mode retention mechanisms of reversed phase and ion exchange prior to reversed-phase LC/MS/MS. In addition to a labeled T3 internal standard (T3-13C9), labeled thyroxine (T4-d5) is also added to serum samples in order to monitor the degradation of T4 to T3. The accuracy of the measurement was evaluated by a recovery study for added T3 and was supported by a comparison study with the other RMP. The recovery of the added T3 ranged from 98.9% to 99.4%. The results of this method and the other RMP agreed to within 1%. Samples of frozen serum pools were prepared and measured in three separate sets. Excellent reproducibility was obtained with within-set coefficients of variation (CVs) ranging from 0.8% to 1.6% and between-set CVs ranging from 1.9% to 2.6%. Excellent linearity was also obtained with correlation coefficients of all linear regression lines (measured intensity ratios vs mass ratios) ranging from 0.9995 to 0.9996. The detection limit at a signal-to-noise ratio of approximately 3 was 1 pg of T3. The T4 degradation during sample preparation was minimized to a small percentage (no more than 3% of the T3 values) by use of antioxidants (ascorbic acid, dithiothreitol, citric acid) and can be accounted for in the T3 measurement process. This well-characterized LC/MS/MS method for total serum T3, which demonstrates good accuracy and precision, low susceptibility to interferences, accountability of the conversion of T4 to T3, and comparability with the other RMP, qualifies as a reference measurement procedure and can be used to provide an accuracy base to which routine methods for T3 can be compared.

Chromatography, Liquid↗
PubMed2004

Development and evaluation of a candidate reference method for the determination of total cortisol in human serum using isotope dilution liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry.

Cortisol is an important diagnostic marker for the production of steroid hormones, and accurate measurements of serum cortisol are necessary for proper diagnosis of adrenal function. A candidate reference method involving isotope dilution coupled with liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been developed and critically evaluated. An isotopically labeled internal standard, cortisol-d(3), was added to serum, followed by equilibration and solid-phase and ethyl acetate extractions to prepare samples for liquid chromatography/mass spectrometry electrospray ionization (LC/MS-ESI) and liquid chromatography/tandem mass spectrometry electrospray ionization (LC/MS/MS-ESI) analyses. (M + H)(+) ions at m/z 363 and 366 for cortisol and its labeled internal standard were monitored for LC/MS. The transitions of (M + H)(+) --> [(M + H)(+) - 2H(2)O] at m/z 363 --> 327 and 366 --> 330 were monitored for LC/MS/MS. The accuracy of the measurement was evaluated by a comparison of results of this candidate reference method on lyophilized human serum reference materials for cortisol [Certified Reference Materials 192 and 193] with the certified values determined by gas chromatography/mass spectrometry reference methods and by a recovery study for the added cortisol. The results of this method for total cortisol agreed with the certified values within 1.1%. The recovery of the added cortisol ranged from 99.8% to 101.0%. This method was applied to the determination of cortisol in samples of frozen serum pools. Excellent precision was obtained with within-set CVs of 0.3%-1.5% and between-set CVs of 0.04%-0.4% for both LC/MS and LC/MS/MS analyses. The correlation coefficients of all linear regression lines ranged from 0.998 to 1.000. The detection limits (at a signal-to-noise ratio of approximately 3-5) were 10 and 15 pg for LC/MS and LC/MS/MS, respectively. This method, which demonstrates good accuracy and precision, and is free from interferences from structural analogues, qualifies as a candidate reference method and can be used as an alternative reference method to provide an accuracy base to which the routine methods can be compared.

Chromatography, Liquid↗
PubMed2004

Impact of reversible trapping of tracer and the presence of blood metabolites on measurements of myocardial glucose utilization performed by PET and 18F-fluorodeoxyglucose using the Patlak method.

In this study we demonstrated that significant egress of FDG from myocardium occurs within the first hour after tracer injection leading to nonlinear Patlak plots. There are also significant amounts of acidic FDG metabolites present in the blood. However, the impact of these metabolites on the estimates of myocardial glucose utilization (MGU) is negligible. Although further studies will be required to elucidate the reason for the egress of tracer from myocardium, not accounting for it will result in erroneous estimates of MGU.

Algorithms↗
PubMed2004

In vivo evaluation of copper-64-labeled monooxo-tetraazamacrocyclic ligands.

Copper-64 (T(1/2)=12.7 h; beta(+): 0.653 MeV, 17.4%; beta(-): 0.578 MeV, 39%) has applications in positron emission tomography (PET) imaging and radiotherapy, and is conveniently produced on a biomedical cyclotron. Tetraazamacrocyclic ligands are the most widely used bifunctional chelators (BFCs) for attaching copper radionuclides to antibodies and peptides due to their relatively high kinetic stability. In this paper, we evaluated three monooxo-tetraazamacrocyclic ligands with different ring sizes and oxo group positions. H1 [1,4,7,10-tetraazacyclotridecan-11-one], H2 [1,4,8,11-tetraazacyclotetradecan-5-one] and H3 [1,4,7,10-tetraazacyclotridecan-2-one] were radiolabeled with (64)Cu in high radiochemical yields under mild conditions. The three (64)Cu-labeled complexes are all +1 charged, as determined by their electrophoretic mobility. While they demonstrated >95% stability in rat serum out to 24 h, both biodistribution and microPET imaging studies revealed high uptake and long retention of the compounds in major clearance organs (e.g., blood, liver and kidney), which suggests that (64)Cu dissociated from the complexes in vivo. Of the three complexes, (64)Cu-2(+), which has a cyclam backbone (1,4,8,11-tetraazacyclotetradecane), exhibited the lowest nontarget organ accumulation. The data from these studies may invalidate the candidacy of the monooxo-tetraazamacrocyclics as BFCs for copper radiopharmaceuticals. However, the data presented here suggest that neutral or negatively charged Cu(II) complexes of tetraazamacrocyclic ligands with a cyclam backbone (tetradecane) are optimal for copper radiopharmaceutical applications.

Animals↗
PubMed2004

Update on PET radiopharmaceuticals: life beyond fluorodeoxyglucose.

Twenty-eight years after its inception, 2-[18F]FDG- is still the most widely used radiopharmaceutical for PET studies, but numerous more specific radiotracers have been developed and applied in neuroscience and oncology. The advances in radiotracer chemistry, especially the nucleophilic substitution reaction, have played the pivotal role in synthesizing various no-carrier-added 18F-labeled radiotracers for PET studies of various receptor systems. This article lists some of the radiotracers that are available for PET studies in neuroscience and oncology. The prospects for developing other new radiotracers for imaging other organ diseases also seem to be promising.

Brain↗