Ac-EAZY! Towards GMP-Compliant Module Syntheses of 225Ac-Labeled Peptides for Clinical Application

The application of 225Ac (half-life T1/2 = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to 90Y, 177Lu or 188Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of 225Ac and its daughter nuclides in tissue is much lower (47–85 μm for alpha energies Eα = 5.8–8.4 MeV), which results in a very precise dose deposition within the tumor. DOTA-conjugated commercially available peptides used for endoradiotherapy, which can readily be labeled with 177Lu or 90Y, can also accommodate 225Ac. The benefits are lower doses in normal tissue for the patient, dose reduction of the employees and environment and less shielding material. The low availability of 225Ac activity is preventing its application in clinical practice. Overcoming this barrier would open a broad field of 225Ac therapy. Independent which production pathway of 225Ac proves the most feasible, the use of automated synthesis and feasible and reproducible patient doses are needed. The Modular-Lab EAZY is one example of a GMP-compliant system, and the cassettes used for synthesis are small. Therefore, also the waste after the synthesis can be minimized. In this work, two different automated setups with different purification systems are presented. In its final configuration, three masterbatches were performed on the ML EAZY for DOTA-TATE and PSMA-I&T, respectively, fulfilling all quality criteria with final radiochemical yields of 80–90% for the 225Ac-labeled peptides.

Evaluation of tube current modulation programms for the optimization of scan protocols in computed tomography

Computed tomography (CT) is commonly associated with relatively high patient doses. In order to keep the patient doses from the CT examinations on the acceptable level it is necessary to apply the principle of optimization. An essential part of optimization is the achievement of the compromise between the patient dose reduction and the maintenance of the image quality that provides accurate diagnostic information. The aim of the study was to determine the relations between the patient doses, CT image quality and the parameters of the tube current modulation program (Auto mA, CareDose and DoseRight) for the examination of the chest. The study was performed on the three most common modern tomographs in Russia: Ingenuity Core 128, Philips; Optima 64, General Electric; Definition AS, Siemens. The anthropomorphic phantom Lungman (Kyoto Kagaku CO., LTD) was used in the study. In order to assess the tube current modulation for the range of tube voltage (80–120 kV), the reference mA∙s (ref. mAs), Noise Index (NI) and Dose Right Index (DRI) were changed for the CareDose (Siemens), Auto mA (GE) and RightDose (Philips), respectively. Estimation of the effective dose was performed using the method from Methodical guidance 2.6.1.2944-11 (MU 2.6.1.2944-11). In order to evaluate the image quality, the noise of a CT image in the mediastinum was selected as the most homogenous for chest region. It was estimated, that for the GE units with Auto mA, the noise of CT image had a liner relationship with NI; the patient dose decreased with the increase of NI. For the Siemens units with CareDose, the noise of CT image decreased with the ref.mAs for the range of tube voltage (80–120 kV); the patient dose was directly proportional to the ref.mAs and increased with the tube voltage. For the Philips units with DoseRight, the noise of CT image decreased with the DRI for the range of tube voltage (80–120 kV); the patient dose was directly proportional to the DRI and had no dependence on the tube voltage. The tube current modulations are proprietary for each manufacturer; it is necessary to consider them for the protocol development. The obtained dependences could be useful for optimization of CT protocols.