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M J Welch

Publications and source records attributed to M J Welch.

At least 109 records · Page 6Linked to original sources
PubMed1995

In vivo measurements of pulmonary angiotensin-converting enzyme kinetics. II. Implementation and application.

We measured pulmonary angiotensin-converting enzyme (ACE) kinetics with fluorine-18 captopril and positron emission tomographic (PET) imaging in five control dogs and in five dogs after 20-30 min of left caudal lobe (LCL) hypoxic ventilation. Time-activity data obtained with PET were interpreted with a compartmental receptor model relating changes in tissue and blood activity to one another within the region. In control dogs, the mean ratio of regional blood flow (measured by PET) between left and right dorsal lung regions was 0.90 +/- 0.16 (SD) vs. 0.54 +/- 0.24 (P < 0.05) in LCL hypoxic dogs. In control dogs, the amount of perfused unbound enzyme normalized to regional extravascular water concentration (Bmax/EVLW) averaged 13.3 +/- 8.9 x 10(-6) mmol ACE/ml EVLW; the ratio of regional values between the left and right sides was 1.02 +/- 0.18. In the LCL hypoxic dogs, Bmax/EVLW was 9.7 +/- 11.3 x 10(-6) mmol/ml hypoxic lung region and the ratio was 0.47 +/- 0.31 (P < 0.05). In control dogs, the coefficient of variation for Bmax/EVLW among regions was only 19 +/- 10%, although the between-dog variation was greater (64 +/- 4%). We conclude that this completely noninvasive method appears to be a promising approach for evaluating the expression of pulmonary ACE in vivo.

Animals↗
PubMed1995

Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays.

UNLABELLED: The purpose of this study was to assess the results of PET with 16 alpha-[18F]fluoro-17 beta-estradiol (FES) and [18F]fluoro-2-deoxy-D-glucose (FDG) to validate the concordance between tumor estrogen-receptor (ER) status as determined by FES-PET and in vitro assays and to assess the relationship between tumor metabolic activity determined by FDG-PET and tumor ER status, both of which may provide information about tumor aggressiveness and prognosis. METHODS: We studied 32 patients with primary breast masses and 21 patients with clinical or radiological evidence of recurrent/metastatic breast carcinoma. A diagnosis of breast carcinoma was subsequently proven in 43 patients (24 primary, 15 metastatic and 4 recurrent tumors). In vitro assessment of ER status was available for 40 malignant lesions (23 primary and 17 metastatic/recurrent). The patients underwent PET with both FES and FDG, and the uptake of each tracer within each lesion was evaluated qualitatively as well as semiquantitatively using the standardized-uptake-value (SUV) method. RESULTS: We found good overall agreement (88%) between in vitro ER assays and FES-PET. This degree of agreement is similar to that observed between replicate in vitro assays (with discordances due to interlaboratory, interassay and specimen variability). We were, however, unable to demonstrate any significant relationship between tumor FDG uptake and ER status or between tumor FDG and tumor FES uptake in these patients. CONCLUSION: These results indicate that in vitro ER assays and/or FES-PET provide unique direct information about breast cancer ER status that cannot be obtained indirectly by FDG-PET.

Breast↗
PubMed1995

RadioimmunoPET: detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody.

UNLABELLED: Detection of tumor foci may be improved by combining the selective tumor-targeting properties of a monoclonal antibody with the superior sensitivity and contrast resolution of PET. METHODS: An anti-colorectal carcinoma monoclonal antibody (MAb 1A3) was labeled with 64Cu, a positron-emitting radionuclide, by use of a bifunctional chelate (bromoacetamidobenzyl-TETA) and evaluated in 36 patients with suspected advanced primary or metastatic colorectal cancer. After radiopharmaceutical injection (5-20 mg protein, 10 mCi 64Cu), PET was performed once or twice, 4 to 36 hr later. All patients had CT scans and 18 patients were also studied with [18F]fluorodeoxyglucose (FDG) PET. RESULTS: In 29 patients, one or more tumor sites (n = 56) were proven, in 5 patients the absence of active tumor was confirmed and in the remaining 2, tumor status is not yet confirmed. Of the 56 confirmed tumor sites, 40 were detected by MAb-PET as foci of increased activity (sensitivity 71%). The positive predictive value of MAb-PET was excellent, ranging from 89% (40/45) to 96% (43/45), depending on the ultimate classification of three image-positive, but as yet unconfirmed tumor sites. Also, MAb-PET detected 11 new occult tumor sites, including 9 small abdominopelvic foci less than 2.0 cm in diameter that were not detected by CT or MRI. There were no complications, but significantly elevated HAMA titers were found in 28% of the 29 patients tested 1 to 12 mo after injection. There was no apparent dose-related effect from 5 to 20 mg MAb 1A3. CONCLUSION: These Phase I/II results suggest that PET with radiolabeled MAbs (radioimmunoPET) may have important applications in clinical oncology, particularly for detecting smaller colorectal tumor foci in the abdomen or pelvis and for determining accurate dosimetry.

Adenocarcinoma↗
PubMed1995

Isotope dilution mass spectrometry as a candidate definitive method for determining total glycerides and triglycerides in serum.

A new isotope dilution mass spectrometric method for total glycerides and triglycerides in human serum is described. Total glycerides are defined as the sum of tri-, di-, and monoglycerides plus free glycerol; triglycerides are defined as the pure triglyceride species. In both determinations, serum samples are supplemented by addition of [13C3]tripalmitin, processed, derivatized, and the abundance ratios of selected ions are determined. Bias is investigated by quantifying the analyte in the same samples under different chromatographic and ionization conditions. The analytes were determined in two human serum pools. The CV for a single measurement ranged from 0.35% to 0.72%, and the relative SEM ranged from 0.10% to 0.34%; there was no significant bias in the measurements. The combination of high precision and absence of significant bias in the results qualify this method for consideration as a Definitive Method as defined by the National Committee for Clinical Laboratory Standards.

Carbon Isotopes↗
PubMed1995

Measurement of regional pulmonary blood flow with PET.

UNLABELLED: We have previously reported a method for measuring regional pulmonary blood flow (PBF) in experimental animals using 15O-water and PET. The method requires withdrawing blood from the pulmonary artery during the PET scan, so that the input function can be estimated for the one-compartment model used to analyze the data. The purpose of the present study was to modify and validate this technique for a more general use in humans. METHODS: PBF was measured after injections of 15O-water in 15 normal subjects and in five patients with reduced cardiac output. In ten of the normal subjects, PBF was also measured after the injection of 68Ga-albumin macroaggregates (MAA). In the five other normal subjects and in the cardiomyopathy patients, PBF was measured twice after two separate 15O-water administrations. The input function was estimated from a region of interest (ROI) over the right ventricle (RV), with corrections when necessary, for time delays between RV and lung tissue. RESULTS: The mean value for PBF in the normal subjects was 121 +/- 32 ml/min/100 ml lung, and was 57 +/- 33 ml/min/100 ml lung in the patients with cardiomyopathy. The correlation between PBF measured with 15O-water and PBF measured with 68Ga-MAA was r = 0.96. There was no significant difference in the mean value for PBF or the ventral-dorsal distribution of PBF when sequential measurements were made in the same individual. PBF increased in general in the ventral-dorsal direction in these supine subjects, although PBF was more evenly distributed in the cardiomyopathy patients. CONCLUSION: Measurement of regional PBF with 15O-water and PET appears to be a valid, noninvasive approach for evaluating the pulmonary perfusion pattern of humans.

Adult↗
PubMed1995

In vitro and in vivo evaluation of copper-64-octreotide conjugates.

UNLABELLED: Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to 111In-DTPA-D-Phe1-octreotide. METHODS: The carboxylic acid moieties on the T bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor. RESULTS: The binding affinities of 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (Kd, 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1-octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1-octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide had uptake in tumors comparable to better than 111In-DTPA-D-Phe1-octreotide. CONCLUSION: Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the affinity of 111In-octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.

Adrenal Glands↗
PubMed1995

Dosimetry of copper-64-labeled monoclonal antibody 1A3 as determined by PET imaging of the torso.

UNLABELLED: We present biodistribution and dosimetry results for 64Cu-benzyl-TETA-MAb 1A3 from 15 human subjects injected with this tracer as determined by serial PET imaging of the torso. METHODS: PET imaging was used to quantify in vivo tracer biodistribution at two time points after injection. Absorbed dosimetry calculated using MIRD-11 and the updated MIRDOSE3 was compared with estimates obtained using rat biodistribution data. RESULTS: By measuring activity concentrations in the torso, and extrapolating for the whole body using standard organ and tissue volumes, we were able to account for 93% of the injected radiopharmaceutical over a range of imaging times from 0 to 36 hr postinjection. Based on PET imaging and the MIRD-11 schema, the liver and spleen are the critical organs with average absorbed doses of 0.12 and 0.10 mGy/MBq (0.44 and 0.39 rad/mCi). The revised MIRDOSE3 scheme yields similar values for these and other organs but also results in a dose of 0.14 mGy/MBq (0.53 rad/mCi) to the heart wall. In the rat, the large intestine is the critical organ at 0.14 mGy/MBq (0.52 rad/mCi), while liver and kidneys each receive 0.11 mGy/MBq (0.41 rad/mCi). Some disparities in absorbed doses determined by these methods are evident but are a result of dissimilar biodistributions in rats and humans. For most organs, rat extrapolated values are higher than the human measurements with PET. CONCLUSION: This study shows that torso PET imaging can quantitatively measure the whole-body biodistribution of a radiopharmaceutical as long as it has relatively slow pharmacokinetics.

Animals↗
PubMed1994

Functional consequences of posttranslational isomerization of Ser46 in a calcium channel toxin.

The venom of the funnel-web spider Agelenopsis aperta contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, omega-Aga-IVB (IVB) and omega-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in A. aperta venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.

Agatoxins↗
PubMed1994

Generally applicable, convenient solid-phase synthesis and receptor affinities of octreotide analogs.

Octreotide, an analogue of the hormone somatostatin, has applications as a therapeutic and imaging agent for somatostatin-positive tumors. We have developed a generally applicable, convenient stepwise solid-phase synthetic protocol for octreotide (D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-threoninol). [Cys(Acm)2,D-Trp(Boc)4,Lys(Boc)5,Thr(tBu)6,Cys(Acm)7, des(threoninol)]-octreotide was assembled by Fmoc solid-phase synthesis and the intramolecular disulfide bond formed by treatment of the resin-bound peptide with thallium trifluoroacetate [Tl(Tfa)3]. Side-chain protection of Trp by the Boc group was found to preserve Trp integrity during Tl(Tfa)3 treatment. The protected peptide was cleaved from the resin by aminolysis with threoninol and purified by semipreparative RP-HPLC. Isolated [D-Trp(Boc)4,Lys(Boc)5,Thr(tBu)6]octreotide had the correct molecular mass ([M+H]+ = 1275 Da) and sequence and was obtained in 14% yield at > 98% purity. [D-Trp(Boc)4,Lys(Boc)5,Thr(tBu)6]octreotide was utilized for the solution-phase synthesis of CPTA-D-Phe1-octreotide, where CPTA is 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid. Cyclic dianhydride of diethylenetriaminepentaacetic acid (DTPA) was coupled to a portion of the protected peptide-resin following disulfide bond formation. The DTPA-conjugated, side-chain-protected peptide was cleaved from the resin by aminolysis with threoninol, side-chain deprotected with trifluoroacetic acid, and purified by semipreparative RP-HPLC. The isolated DTPA-D-Phe1-octreotide had the correct molecular mass ([M+H]+ = 1395 Da) and was obtained in 5% yield at > 90% purity. The efficiency of aminolysis was partially dependent upon the linkage between 4-(hydroxymethyl)phenoxy (HMP) handles and the resin and/or resin particle size. The somatostatin receptor binding affinities of synthetic DTPA-D-Phe1-octreotide and CPTA-D-Phe1-octreotide to AtT-20 mouse pituitary carcinoma cell membranes were examined by labeling with 111In and 64Cu, respectively, and performing Scatchard analyses. The dissociation constant (Kd) for our synthetic [111In]DTPA-D-Phe1-octreotide was 4.31 nM, which is comparable to a Kd = 5.57 nM obtained with commercially available DTPA-D-Phe1-octreotide. The Kd for [64Cu]CPTA-D-Phe1-octreotide was 78.5 pM. On the basis of the criteria of molecular mass, RP-HPLC elution time, sequence analysis, and somatostatin receptor binding affinity, our synthetic octreotide is identical to commercially available octreotide. The aminolysis protocol used here has distinct advantages over either reductive cleavage or preformed linker methods described previously for the preparation of octreotide.

Amines↗
PubMed1994

Synthesis and tissue biodistribution of [omega-11C]palmitic acid. A novel PET imaging agent for cardiac fatty acid metabolism.

In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, we have developed a synthesis of [omega-11C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [11C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rats comparing [omega-11C]palmitic acid and [1-11C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [omega-11C]palmitic acid is approximately 50% greater than after administration of [1-11C]palmitic acid, due to the diminished metabolism of the [omega-11C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [omega-11C]-and [1-11C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.

Acyl-CoA Dehydrogenase↗
PubMed1994

Homodimeric and heterodimeric bis(amino thiol) oxometal complexes with rhenium(V) and technetium(V). Control of heterodimeric complex formation and an approach to metal complexes that mimic steroid hormones.

We have investigated the possibility of preparing complexes of rhenium and technetium whose shape resembles that of ligands for steroid receptors. The general structure of N2S2 complexes of oxorhenium(V) and oxotechnetium(V) is such that they could replace the BC ring system of steroid, thereby generating a metal complex system with considerable size and shape similarity to a steroid. Such a metal-integrated steroid-shaped complex can be constructed as a heterodimer of two different amino thiols; complexes of rhenium and technetium with such heterodimeric bis-bidentate structure have not been systematically studied. In this investigation, we have shown that complexes of this nature form readily when appropriate metal precursors are combined with a mixture of amino thiols. In the systems we have studied, heterodimeric complex formation is preferred over homodimeric complex formation, and in one system where we were able to obtain an X-ray crystal structure, this oxorhenium heterodimer had the desired trans geometry. These rhenium and technetium-99m complexes are reasonably stable toward ligand exchange; they can be readily purified by chromatography under appropriate conditions, and the one technetium-99m complex studied in vivo shows some persistence in blood and gives good initial uptake in several tissues. The convenient and selective formation of such bis-bidentate heterodimeric complexes suggests that the development of metal-integrated complexes that resemble ligands for receptors may be possible.

Animals↗
PubMed1994

The synthesis of 7 alpha-methyl-substituted estrogens labeled with fluorine-18: potential breast tumor imaging agents.

The 7 alpha-methyl substituent is reported to increase the binding affinity of estradiol for the estrogen receptor (ER). In order to evaluate whether this substituent would improve the in vitro binding characteristics and the in vivo tissue distribution of 18F labeled estrogens that we are developing as positron emission tomographic (PET) imaging agents for ER-positive breast tumors, we have prepared four 18F labeled analogs of 7 alpha-methylestradiol. These ligands were labeled in the 16 alpha or 16 beta position with 18F by nucleophilic displacement of the corresponding epimeric estrone trifluoromethanesulfonates with 18F fluoride ion. Lithium aluminum hydride reduction afforded the estradiol (E2) series, while lithium trimethylsilylacetylide addition provided the 17 alpha-ethynylestradiol (EE2) series. The decay-corrected yields were 2-35% for a synthesis time of 85 minutes for the E2 series, and 120 minutes for the EE2 series, and the effective specific activities were 158-1213 Ci/mmol. In nearly every case, the 7 alpha-methyl substituent increases ER binding affinity (measured at 25 C) and decreases binding to high affinity serum steroid binding proteins, alphafetoprotein, and sex steroid binding protein; this substituent, however, increases the lipophilicity and the predicted non-specific binding (estimated from octanol-water partition coefficients determined by reverse-phase high-pressure liquid chromatography/[HPLC]), with the result that the ratio of ER binding to non-specific binding is nearly the same for the 7 alpha-methyl substituted analogs as for the corresponding unsubstituted analogs. In vivo distribution studies demonstrated a high level of receptor-mediated uptake in receptor-rich target tissues (uterus, ovaries), and in some cases, other tissues with low ER titers (secondary target tissues, e.g., muscle, thymus) showed significant displaceable uptake, presumed to be receptor-mediated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evaluation of a direct method for technetium labeling intact and F(ab')2 1A3, an anticolorectal monoclonal antibody.

A direct method for 99mTc-labeling monoclonal antibodies (MAb) has been evaluated for labeling intact and F(ab')2 1A3, an anticolorectal carcinoma MAb. The method employs ascorbic acid to reduce the MAbs. By altering the reaction conditions for 99mTc-1A3, a maximum radiolabeling yield of 48% was obtained with an immunoreactivity (IR) value of 87%; and for 99mTc-1A3-F(ab')2, a yield of 49% and an IR value of 70% was obtained. Biodistribution of 99mTc-labeled 1A3 MAbs was performed in a Golden Syrian hamster model and compared to 125I-labeled 1A3 MAbs. Tumor uptake (%ID/g) was significantly better for the intact 125I-1A3 at 24 h post-injection compared to the intact 99mTc-1A3. For 99mTc-1A3-F(ab')2, %ID/g tumor was low, and did not increase over 24 h. High %ID/g kidney persisted at 24 h for both 99mTc-labeled intact and F(ab')2 1A3. Serum stability was performed in Sprague-Dawley rats for the 99mTc-labeled 1A3 MAbs, and compared to 125I-labeled 1A3 MAbs, which showed intact 99mTc-1A3 cleared similarly to 125I-1A3, and 99mTc-1A3-F(ab')2 cleared more rapidly than 125I-1A3-F(ab')2 indicating instability of the 99mTc-labeled 1A3-F(ab')2.

Animals↗
PubMed1994

A windowless 13N production target for use with low energy deuteron accelerators.

The recent development of low energy accelerators for positron emission tomography has necessitated the development of new targets for 13N production. 12C(d,n)13N reaction yields in graphite at low deuteron beam energies (0.8-3.2 MeV) are presented and a new technique for the in situ extraction of 13N activity from solid graphite and subsequent conversion to [13N] ammonia is described. The target is windowless and is reusable for multiple isotope production runs. This technique utilizes radio frequency induction heating to rapidly heat the graphite to combustion temperatures in an O2 gas stream. The conversion of activity induced in the target to [13N] ammonia in under 10 min with an overall decay-corrected efficiency of 45% is reported.

Ammonia↗
PubMed1994

Production of [13N]ammonia applicable to low energy accelerators.

We have developed a technique for the rapid conversion of the nitrogen-13 induced in a graphite target into nitrogen oxides. This was accomplished by heating the graphite target in a stream of pure oxygen at 800 degrees C. Less than 20% of the radioactivity was found in the form of [13N]nitrogen. The rest of the radioactivity was efficiently trapped in a solid-phase medium that consisted of an aqueous solution of 5% NaOH dispersed in silica gel. The radioactivity from this solid-phase medium was eluted with water (94% recovery) and found to be in the form of 13NO2- (99%). This was subsequently converted to [13N]ammonia with Raney-nickel, either by a conventional liquid-phase reduction with an overall conversion efficiency to ammonia of 45%, or by an incorporation of the Raney-nickel into the solid-phase medium. The latter system resulted in an overall conversion efficiency to ammonia of 37 +/- 9%, with a radiochemical purity of nearly 100% and a synthesis time under 17 min.

Ammonia↗
PubMed1994

Oxohexestrol derivatives labeled with fluorine-18. Synthesis, receptor binding and in vivo distribution of two non-steroidal estrogens as potential breast tumor imaging agents.

We have prepared two non-steroidal estrogens in the 2-oxohexestrol series labeled with the positron-emitting radionuclide fluorine-18, 1-fluoro-5-oxohexestrol (4) and 1-fluoro-2-oxohexesterol (5). We anticipated that the polar ketone function at the interior of these ligands would reduce their level of non-specific binding, which might increase the selectivity of their uptake in vivo. The two compounds were prepared by total synthesis: compound 4 was prepared in fluorine-18 labeled form by [18F]fluorine ion displacement on a suitably protected methanesulfonate precursor followed by deprotection under acidic hydrogenolytic conditions; the isomer 5 was prepared from a protected alpha-keto trifluoromethanesulfonate precursor with deprotection under basic conditions as the final step. The binding affinity of these hexestrol derivatives for the estrogen receptor was determined by competitive radiometric binding assays at 0 and 25 degrees C, and their lipophilicity (as octanol-water partition coefficients, log P values) and non-specific binding were estimated. The log P values determined by a reversed phase HPLC method were higher, relative to estradiol, than those calculated by the fragment method of Rekker. In tissue distribution studies in immature (50 g) rats, both of these compounds showed selective uptake in estrogen target tissues. At 1 h, activity in the uterus reached the level of 2.5-3.0% of the injected dose per gram tissue, with uterus-to-blood and uterus-to-muscle ratios of 14-20 and 8-14, respectively. The uptake efficiency and selectivity of these fluoro-oxohexestrols in principal estrogen target tissues is less than that of fluorine-18 labeled steroidal estrogens we have prepared previously, but their receptor-mediated uptake in certain secondary target tissues is substantial. The specific and non-specific components of target tissue uptake of these two compounds appear to be directly related to their non-specific binding and their binding selectivity.

Animals↗
PubMed1994

First-pass extraction fraction of iodine-123 labeled perfusion tracers in living primate brain.

The cerebral extraction and retention of three radioiodinatéd SPECT perfusion tracers were measured using residue detection in a baboon. A permeability-surface area product PS' with special relevance to SPECT was calculated from the retention of tracer in the brain after 10 min. PS' differs from the traditional PS value, which is calculated from the tracer clearance curve at 2 min. The PS' values ranged from 50 to 95 mL/min/100 g, decreased in the order [123I]IMP > [123I]iodoperidol approximately [123I]HIPDM, and did not differ for specific activities of 10 MBq/mmol to 74 TBq/mmol. These radioiodinated compounds exhibited extraction characteristics superior to those of [99mTc]HMPAO but underestimated cerebral blood flow when flows were above 20-30 mL/min/100 g, underscoring the need for development of a more ideal SPECT perfusion tracer.

Animals↗