Semi-automated system for concentrating 68Ga-eluate to obtain high molar and volume concentration of 68Ga-Radiopharmaca for preclinical applications

Introduction: 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

The inhibitory effect of ¹¹¹In-DTPA⁰-octreotide on intrahepatic tumor growth after partial hepatectomy

The 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 &lt; 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 &lt; 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 ¹¹¹In-DTPA⁰-octreotide on intrahepatic tumor growth after partial hepatectomy

The 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 &lt; 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 &lt; 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