Background-aim: 68Gallium (68Ga)-peptides-based PET-CT is an emerging procedure for the management of neuroendocrine tumors. Its highest accuracy in assessing lesions over-expressing somatostatin receptors has currently set aside the traditional Indium-111 (111In)- Pentreotide (OctreoScanÒ) scintigraphy. We are herein to describe the development and validation of an automated method to radiolabel 68Ga with the somatostatin analogue DOTATOC, by using a specific cassette, designed for single use application, and suitable for the Scintomics-GRPÒ synthesizer distributed by the MecMurphyl Company. Methods: All the steps concerning the radiolabeling phase—as long as the tests for the quality control or the management of radioactive waste or, finally, the traceability of the entire procedure—have been carried out and standardized according to the current National Reg- ulation on the use of radiopharmaceuticals (NBP-MN, GU n. 168 del 21 luglio 2005 and Farmacopea Ufficiale-Current Edition). The identification (and application) of the best standard procedure obtainable using this automated synthesis modality has involved more than 3 months and the cooperation of a dedicated team-work including MecMurphyl Company’s specialists, and Nuclear Medicine physicians, technicians and physicists of our Unit. In particular, Nuclear Medicine technicians have had a central role both in the synthesis and in the quality control of 68Ga-DOTATOC. Results: After the preliminary phase, concerning the qualification and the validation of the automated procedure of 68Ga-DOTATOC radio- labeling, the Nuclear Medicine technician staff has maintained its essential role by performing 42 radiolabeling procedures of 68Ga- DOTATOC: 38 out 42 procedures have been successfully completed allowing a proper PET-TC evaluation in 56 patients. In only 4 cases the radiolabeling procedure has failed, but in no case the failure was due to any non-compliance of the procedure or from mistakes by the opera- tors. Rather, the errors were caused by unexpected technical faults of the instruments, for example, during a session, there has been a sudden drop of electricity voltage that has blocked the software controlling the synthesizer and made the procedure failed. However, consequent improvement actions have been elaborated from each of these failures. The stability and reproducibility of the novel method of radiolabeling have been confirmed by the positive results arising from the various quality checks performed on any preparations. In particular, as required by Current Pharmacopeia standard, radiochemical purity of 68Ga- DOTATOC has always been in values of 96.74 ± 1.03% compared with the value of 68Ga-colloid of 0.96 ± 0.49%, and the absence of free-68Ga confirmed in any procedure. Conclusions: The acquisition of a proper expertise in automated radiolabelling procedure for 68Ga-DOTATOC has been pivotal for the operators of our Nuclear Medicine Unit and preparatory to further automated productions of radiopharmaceuticals for therapeutic use, as 90Y/177Lu-DOTATOC. We underline the crucial role of the Nuclear Medicine technician who is going ho have a key role in the Thera- nostics of neuroendocrine tumors.

Methodology and technical implementation of a procedure for automated production 68Ga-DOTATOC

L. Uccelli;FARINA, DONATELLA;C. Cittanti;M. Bartolomei
2017

Abstract

Background-aim: 68Gallium (68Ga)-peptides-based PET-CT is an emerging procedure for the management of neuroendocrine tumors. Its highest accuracy in assessing lesions over-expressing somatostatin receptors has currently set aside the traditional Indium-111 (111In)- Pentreotide (OctreoScanÒ) scintigraphy. We are herein to describe the development and validation of an automated method to radiolabel 68Ga with the somatostatin analogue DOTATOC, by using a specific cassette, designed for single use application, and suitable for the Scintomics-GRPÒ synthesizer distributed by the MecMurphyl Company. Methods: All the steps concerning the radiolabeling phase—as long as the tests for the quality control or the management of radioactive waste or, finally, the traceability of the entire procedure—have been carried out and standardized according to the current National Reg- ulation on the use of radiopharmaceuticals (NBP-MN, GU n. 168 del 21 luglio 2005 and Farmacopea Ufficiale-Current Edition). The identification (and application) of the best standard procedure obtainable using this automated synthesis modality has involved more than 3 months and the cooperation of a dedicated team-work including MecMurphyl Company’s specialists, and Nuclear Medicine physicians, technicians and physicists of our Unit. In particular, Nuclear Medicine technicians have had a central role both in the synthesis and in the quality control of 68Ga-DOTATOC. Results: After the preliminary phase, concerning the qualification and the validation of the automated procedure of 68Ga-DOTATOC radio- labeling, the Nuclear Medicine technician staff has maintained its essential role by performing 42 radiolabeling procedures of 68Ga- DOTATOC: 38 out 42 procedures have been successfully completed allowing a proper PET-TC evaluation in 56 patients. In only 4 cases the radiolabeling procedure has failed, but in no case the failure was due to any non-compliance of the procedure or from mistakes by the opera- tors. Rather, the errors were caused by unexpected technical faults of the instruments, for example, during a session, there has been a sudden drop of electricity voltage that has blocked the software controlling the synthesizer and made the procedure failed. However, consequent improvement actions have been elaborated from each of these failures. The stability and reproducibility of the novel method of radiolabeling have been confirmed by the positive results arising from the various quality checks performed on any preparations. In particular, as required by Current Pharmacopeia standard, radiochemical purity of 68Ga- DOTATOC has always been in values of 96.74 ± 1.03% compared with the value of 68Ga-colloid of 0.96 ± 0.49%, and the absence of free-68Ga confirmed in any procedure. Conclusions: The acquisition of a proper expertise in automated radiolabelling procedure for 68Ga-DOTATOC has been pivotal for the operators of our Nuclear Medicine Unit and preparatory to further automated productions of radiopharmaceuticals for therapeutic use, as 90Y/177Lu-DOTATOC. We underline the crucial role of the Nuclear Medicine technician who is going ho have a key role in the Thera- nostics of neuroendocrine tumors.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/2382590
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