Gallium-68 Labeling of Albu Min and Albumin Microspheres

Wagner, Sally; Welch, Michael J.

doi:10.1097/00004728-197910000-00053

Cited by 15 publications

(21 citation statements)

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“…The possibilities that the 1 ~ lln activity of this fraction was the result of proteolysis and that 11 ~In was bound to antibody metabolites via DTPA were excluded by the fact that free DTPA deprived the I fraction of lllIn but not the IgG fraction. Similar observations have been reported by several authors (Wagner and Welch 1979;Paik et al 1980;Hnatowich 1986;Deshpande et al 1990b;Khaw et al 1990). Wagner and Welch (1979) reported lllln bound to DTPA-HSA conjugate was exchanged to transferrin about 9% per day in the presence of 250 mg/dl of transferrin in 0.1 M NaOH, pH 5.5.…”

Section: Discussionsupporting

confidence: 90%

In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism

et al. 1992

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The effects of diethylene triamine penta-acetic acid (DTPA) on indium-111 monoclonal antibody (MoAb) metabolism were examined. Sequential analysis of 111In-MoAb incubated in serum at 37 degrees C by high performance liquid chromatography (HPLC) and electrophoresis revealed that the radioactivity gradually moved from the MoAb to a 70-90 kDa molecular weight fraction. DTPA inhibited the transchelation of 111In to this fraction. It also decreased 111In uptake by isolated rat hepatocytes but did not remove 111In incorporated in hepatocytes. The daily in vivo administration of DTPA (0.5-2.0 mg/mouse daily) to athymic mice after 111In-MoAb injection significantly reduced the 111In uptake in the liver and kidney. The tumour uptake was decreased somewhat but not significantly. The serum radioactivity in the 70-90 kDa fraction was also decreased. Scintigraphic examination demonstrated a decreased liver uptake in the DTPA-treated group of mice. Our results show that 111In released from the DTPA-MoAb conjugate in serum binds to molecules of 70-90 kDa and that DTPA decreases the 111In uptake in this fraction, which induces a decrease of 111In accumulation in normal tissues.

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Section: Discussionsupporting

confidence: 90%

In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism

et al. 1992

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“…We used 68 Ga, whose physical half-life (67,629 min) is well suited for PET studies (22,35,38). The ␤ ϩ range of 68 Ga does not impair spatial resolution by more than 2.4 mm, and the fraction of additional ␥-radiation is low (3%), which suggests a comparatively low radiation dose.…”

Section: Data Acquisition and Analysismentioning

confidence: 99%

“…Their spatial distribution therefore reflects pulmonary blood flow (PBF; Refs. 11,13,14,20,32,38). Data analysis for colored or fluorescent microspheres requires lung excision and post mortem processing.…”

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confidence: 99%

Effects of posture on regional pulmonary blood flow in rats as measured by PET

Richter

Bergmann

Pietzsch

et al. 2010

Journal of Applied Physiology

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Using small animal PET with 68 Ga-radiolabeled human albumin microspheres (Ga-68-microspheres), we investigated the effect of posture on regional pulmonary blood flow (PBF) in normal rats. This in vivo method is noninvasive and quantitative, and it allows for repeated longitudinal measurements. The purpose of the experiment was to quantify spatial differences in PBF in small animals in different postures. Two studies were performed in anesthetized, spontaneously breathing Wistar rats. Study 1 was designed to determine PBF in the prone and supine positions. Ga-68-microspheres were given to five prone and eight supine animals. We found that PBF increased in dorsal regions of supine animals (0.75) more than in prone animals (0.70; P ϭ 0.037), according to a steeper vertical gradient of flow in supine than in prone animals. No differences in spatial heterogeneity were detected. Study 2 was designed to determine the effects of tissue distribution on PBF measurements. Because microspheres remained fixed in the lung, PET was performed on animals in the position in which they received Ga-68-microsphere injections and thereafter in the opposite posture. The distribution of PBF showed a preference for dorsal regions in both positions, but the distribution was dependent on the position during administration of the microspheres. We conclude that PET using Ga-68-microspheres can detect and quantify regional PBF in animals as small as the rat. PBF distributions differed between the prone and supine postures and were influenced by the distribution of lung tissue within the thorax. pulmonary blood flow; positron emission tomography;68 Ga radiolabel; human serum albumin microspheres; prone position; supine position; small animal COLORED OR FLUORESCENT MICROSPHERES have primarily been used for blood flow measurements in small animals. Intravenously administered microspheres larger than 10 m are predicted to become trapped in the pulmonary capillaries. Their spatial distribution therefore reflects pulmonary blood flow (PBF; Refs. 11,13,14,20,32,38). Data analysis for colored or fluorescent microspheres requires lung excision and post mortem processing. In contrast, by using radiolabeled microspheres, data for the blood flow distribution could be achieved noninvasively and in vivo (22,35). A major advantage of positron emission tomography (PET) is its high sensitivity and the ability to quantify the concentration of radiotracers in the lung (24). The use of a dedicated small animal PET could allow this method to be translated to rodents. Therefore, we tested the feasibility of measuring PBF in rats using biodegradable, 68 Ga-radiolabeled human serum microspheres (Ga-68-microspheres) and micro-PET.Subsequently, and with a variety of radiotracers, positional changes in regional blood flow from upper to lower regions have been found in large animals and humans (4,15,23,25,33,36). However, to the best of our knowledge there are no data regarding the influence of posture (prone and supine) on regional pulmonary blood flow in small a...

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“…Albumin microsphere labeling with 68 Ga can be effectively achieved either by hydrolysis and precipitation of the 68 Ga 3+ ion in the presence of the albumin particles (Chester, et al, 1975;Hnatowich, 1976;Yvert, et al, 1979;Hayes, et al, 1981;Maziere, et al, 1986;Mintun, et al, 1986;Schuster and Green, 1987), or by covalent conjugation of the microspheres with a high-affinity gallium chelating ligand (Wagner and Welch, 1979). When the FDA-approved 99m Tc-human serum albumin microsphere product was withdrawn from the U.S. market, the 68 Ga-labeling method for albumin microspheres was adapted for use with the commercial kits available for the preparation of [ 99m Tc]Tc-MAA (macroaggregared human serum albumin) (Even and Green, 1989).…”

Section: Introductionmentioning

confidence: 99%

A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer

Mathias

Green

2008

Applied Radiation and Isotopes

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A convenient method is described for compounding [ 68 Ga]Ga-MAA (MAA = macroaggregated human serum albumin) with the eluate of a commercially available TiO 2 -based 68 Ge/ 68 Ga generator. The final [ 68 Ga]Ga-MAA product was obtained with an 81.6 ± 5.3% decay-corrected radiochemical yield and a radiochemical purity of 99.8 ± 0.1% (n = 5). Microscopic examination showed the [ 68 Ga]Ga-MAA product to remain within the original particle size range. The entire procedure, from generator elution to delivery of the final [ 68 Ga]Ga-MAA suspension, could be completed in 25 minutes. Only 4.4 ± 0.9% of the total 68 Ge breakthrough remaining associated with the final [ 68 Ga] Ga-MAA product. The procedure allows reasonably convenient preparation of [ 68 Ga]Ga-MAA in a fashion that can be readily adapted to sterile product compounding for human use.

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Gallium-68 Labeling of Albu Min and Albumin Microspheres

Cited by 15 publications

References 0 publications

In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism

In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism

Effects of posture on regional pulmonary blood flow in rats as measured by PET

A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer

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