12 research outputs found
Scaled-up radiolabelling of DOTATATE with 68Ga eluted from a SnO2-based 68Ge/68Ga generator
No full textA scaled-up radiolabelling and improved post-labelling purification procedure for [Ga-68]DOTATATE is reported, using a more than 1 year old SnO2-based 1850 MBq Ge-68/Ga-68 generator (initially double-loaded with 3700 MBq Ge-68) as a source of ionic Ga-68. The elution method of choice comprised elution with 0.6 M HCl in a single 4 mL fraction, containing up to 95% of the total eluted Ga-68 activity. The unpurified fraction was directly used for labelling after pH adjustment with 2.5 M sodium acetate. Labelling efficiencies were determined at 90-95 degrees C at various reaction times and reaction volumes of up to 5.7 mL, using either 30 mu g or 50 mu g DOTATATE. Only the latter amount resulted in consistently high labelling efficiency in excess of 95%. Post-labelling purification, carried out on Sep-Pak C18, showed that 50% ethanol in saline was a superior desorption eluant than 100% ethanol. The highest and most consistent decay-corrected radiochemical yields (89%) were obtained using 50 mu g DOTATATE and a 20 min reaction time. (C) 2011 Elsevier Ltd. All rights reserved
The inhibitory effect of <sup>111</sup>In-DTPA<sup>0</sup>-octreotide on intrahepatic tumor growth after partial hepatectomy
Get PDFThe aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with 111In -diethylenetriaminepentaacetic acid (DTPA)0-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). Methods: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 μg/kg subcutaneously twice daily or with 370 MBq 111In-DTPA0-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of 111In-DTPA0-octreotide therapy on liver regeneration after PHx. Results: PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. 111In-DTPA0-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). 111In-DTPA0-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, 111In-DTPA0-octreotide therapy did not influence liver regeneration or liver function after PHx. Conclusion: Peptide receptor radionuclide therapy with 111In-DTPA0octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.</p
The inhibitory effect of <sup>111</sup>In-DTPA<sup>0</sup>-octreotide on intrahepatic tumor growth after partial hepatectomy
Get PDFThe aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with 111In -diethylenetriaminepentaacetic acid (DTPA)0-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). Methods: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 μg/kg subcutaneously twice daily or with 370 MBq 111In-DTPA0-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of 111In-DTPA0-octreotide therapy on liver regeneration after PHx. Results: PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. 111In-DTPA0-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). 111In-DTPA0-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, 111In-DTPA0-octreotide therapy did not influence liver regeneration or liver function after PHx. Conclusion: Peptide receptor radionuclide therapy with 111In-DTPA0octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.</p
The inhibitory effect of <sup>111</sup>In-DTPA<sup>0</sup>-octreotide on intrahepatic tumor growth after partial hepatectomy
Get PDFThe aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with 111In -diethylenetriaminepentaacetic acid (DTPA)0-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). Methods: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 μg/kg subcutaneously twice daily or with 370 MBq 111In-DTPA0-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of 111In-DTPA0-octreotide therapy on liver regeneration after PHx. Results: PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. 111In-DTPA0-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). 111In-DTPA0-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, 111In-DTPA0-octreotide therapy did not influence liver regeneration or liver function after PHx. Conclusion: Peptide receptor radionuclide therapy with 111In-DTPA0octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.</p
Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides
No full textObjectives: PET scintigraphy with (68)Ga-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO(2)-based (68)Ge/(68)Ga generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated. Methods: Characteristics of 4 SnO(2)-based generators (range 0.4-1 GBq (68)Ga in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO(2)-based (68)Ge/(68)Ga generators were monitored, while [HCl] of the eluens was varied from 0.3-1.0 M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the (68)Ga eluate were performed using anion and cation exchange. Concentrated (68)Ga eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. (68)Ga-DOTA-TATE-containing solution was purified and RNP increased by SPE, therefore also 11 commercially available SPE columns were investigated. Results: The amount of elutable (68)Ga activity varies when the concentration of the eluens, HCl, was varied, while (68)Ge activity remains virtually constant. SnO(2)-based (68)Ge/(68)Ga generator elutes at 0.6 M HCl > 100% of the (68)Ga activity at calibration time and +/- 75% after 300 days. Eluate at discharge was sterile and Endotoxins were 80%). Highest desorption for cation purification was obtained using a solution containing 90% acetone at increasing molarity of HCl, resulted in a (68)Ga desorption of 68 +/- 8%. With all (68)Ge/(68)Ga generators and for all 3 purification methods a SA up to 50 MBq/nmol with > 95% incorporation (ITLC) and RCP (radiochemical purity) by HPLC +/- 90% could be achieved. Purification and concentration of the eluate with anion exchange has the benefit of more elutable (68)Ga with 1 M HCl as eluens. The additional washing step of the anion column with NaCl and ethanol, resulted in a lower and less variable [H(+)] in the eluate, and, as a result the pH in the reaction vial is better controlled, more constant, and less addition of buffer is required and concordant smaller reaction volumes. Desorption of (68)Ga-DOTA-TATE of SPE columns varied, highest desorption was obtained with Baker C(18) 100 mg (84%). Purification of (68)Ga-DOTA-TATE by SPE resulted in an RNP of 95% incorporation and a RCP of +/- 90%. SPE columns are very effective to increase RNP. (C) 2010 Elsevier Ltd. All rights reserved
68Ga-labeled DOTA-Peptides and 68Ga-labeled Radiopharmaceuticals for Positron Emission Tomography: Current Status of Research, Clinical Applications, and Future Perspectives
No full textIn this review we give an overview of current knowledge of (68)Ga-labeled pharmaceuticals, with focus on imaging receptor-mediated processes. A major advantage of a (68)Ge/(68)Ga generator is its continuous source of (68)Ga, independently from an on-site cyclotron. The increase in knowledge of purification and concentration of the eluate and the complex ligand chemistry has led to (68)Ga-labeled pharmaceuticals with major clinical impact. (68)Ga-labeled pharmaceuticals have the potential to cover all today's clinical options with (99m)Tc, with the concordant higher resolution of positron emission tomography (PET) in comparison with single photon emission computed tomography. (68)Ga-labeled analogs of octreotide, such as DOTATOC, DOTANOC, and DOTA-TATE, are in clinical application in nuclear medicine, and these analogs are now the most frequently applied of all (68)Ga-labeled pharmaceuticals. All the above-mentioned items in favor of successful application of (68)Ga-labeled radiopharmaceuticals for imaging in patients are strong arguments for the development of a (68)Ge/(68)Ga generator with Marketing Authorization and thus to provide pharmaceutical grade eluate. Moreover, now not one United States Food and Drug Administration approved or European Medicines Agency approved (68)Ga-radiopharmaceutical is available. As soon as these are achieved, a whole new radiopharmacy providing PET radiopharmaceuticals might develop. Semin Nucl Med 41:314-321 (C) 2011 Elsevier Inc. All rights reserved
Semi-automated system for concentrating 68Ga-eluate to obtain high molar and volume concentration of 68Ga-Radiopharmaca for preclinical applications
Get PDFIntroduction: 68Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semi-automatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity. Methods: To purify Gallium-68 and to reduce the high elution volume of a 68Ga-generator, a NaCl-based method using a column containing PS-H+ was implemented in a low volume PEEK system. Influence on reducing osmolality, acidity and the amount of PS-H+ resin (15–50 mg) was investigated. [68Ga]Ga was desorbed from the PS-H+ resin with acidified 2-5 M NaCl (containing 0.05 M of HCl) and 68Ga-activity was collected. DOTA-TATE was used as a peptide model. All buffers and additives used for labeling were mixed with Chelex 100 (~1 g/50 mL) for >144 h and eventually filtered using a 0.22 μm filter (Millipore). Quantification of metals was performed after labeling by HPLC (UV). Results: Gallium-68 activity could be desorbed from PS-H+ cation column with 3 M NaCl, and >60% (120–180 MBq) of [68Ga]Ga was collected in 99% (ITLC), and a radiochemical purity of >95% (HPLC). Conclusion: With the here described concentration system and metal purification technique, a low activity containing 68Ga-generator can be used to label DOTA-peptide in preclinical applicable amounts >60 MBq/nmol (40–60 MBq/0.1 mL) and within 20 min
Lanthanide(III) Complexes of Bis(phosphonate) Monoamide Analogues of DOTA: Bone-Seeking Agents for Imaging and Therapy
No full textLanthanide complexes of DOTA derivatives 2a (BPAMD) and 2b (BPAPD), having a monoamide pendant arm with a bis(phosphonate) moiety, were comparatively tested for application in MRI, radiotherapy, and bone pain palliation. 1H, 31P, and 17O NMR spectroscopy show that they are nine-coordinated, with one water molecule in the first coordination sphere of the Ln(III) ion. The bis(phosphonate) moieties are not coordinated to the lanthanide and predominantly mono- and diprotonated at physiological pH. The parameters governing the longitudinal relaxivities of the Gd complexes are similar to those of other monoamides of DOTA reported in the literature. Upon adsorption on hydroxyapatite, the relaxivities at 20 MHz and 25 °C of Gd-2a and Gd-2b were 22.1 and 11 s−1 mM−1, respectively. An in vivo γ-ray imaging study showed that the 177Lu complexes of 2a and 2b have a high affinity for bones, particularly for growth plates and teeth with a prolonged retention
The mineralogy, geochemistry, and petrogenesis of the grønnedal-íka alkaline igneous complex, south-west Greenland
Get PDFAt 1299±17 Ma (Blaxland et al, 1978), the Grønnedal-Íka is the oldest of the Gardar centres, situated in the extreme north-west of the province. Hare-earth clement (REE) trends suggest that the nepheline-syenites which make up the bulk of the complex were derived from a parental magma formed by a few percent of partial melting of a garnet-lherzolite mantle source during an episode of rifting in the Early Gardar. In contrast to other undersaturated Gardar centres, the syenites of Gronnedal-l'ka show some striking raineralogical differences. The scarcity of amphibole and lack of olivine indicate a magma with a relatively high oxygen fugacity. Opaque oxide compositions and pyroxene trends provide further support for this idea. Additionally, the occurrence of zircon in all units of the complex is unusual, and is probably related to post-magmatic alteration processes. Fractionation of apatite and zircon appears to have been responsible for the observed variations in REE content, although later iteration and variations in the composition of the inter- cumulus liquid have given rise to a considerable scatter in major and trace element abundances. Normative compositions show the evidence for the development of a 'sandwich' horizon in both the Lower and Upper Series. At a later stage, a plug of xenolithic syenite was intruded, which was followed by a the em placement of a body of xenolithic carbonatite, containing fragments of the earlier syenites. This unit is predominantly s0vitic, but with increasing fractionation, more iron-rich (ferrcarbonatite) compositions were developed. Compared to many carbonatites, the rock at Grønnedal is rather poor in 'exotic' minerals. Trace element abundances, however, show extreme enrichment in Sr, Th, REE's, and Y, and depletion in Zr, Ti, and K compared to the syenites. These variations are comparable to the observed concentrations in the Igaliko carbonatite dykes (Pearce, 1988). Hf, Ta, and REE distributions between the carbonatite and syenitic rocks suggest that the carbonatite was derived by liquid immiscibility from a Co(_2)-saturated phonolitic magma, with the conjugate silicate phase possibly intruded as the Xenolithic Porphyritc Syenite. Patchy metasomatic alteration has affected all units, and has given rise to the Coarse- Grained Brown Syenite, which occurs in both the Lower and Upper Series. More intense alteration has affected the syenites, giving carbonate-rich 'carbosyenites', and xenoliths of country rock within the syenites and carbonatite; the surrounding country-rock is not as severely affected as might have been expected. The presence of zircon, alkali mafics, sodalite veins, and recrystallisation of feldspar in the altered rocks is attributed to the effects of peradkaline. C1 and C0(_2)-rich late-stage fluids derived from both the syenites and carbonatite
