Background: PET nuclides can have a considerable influence on the spatial resolution and image quality of PET/CT scans, which can influence diagnostics in oncology, for example. The individual impact of the positron energy of ¹⁸F, ⁶⁸Ga, and ⁶⁴Cu on spatial resolution and image quality was compared for PET/CT scans acquired using a clinical, digital scanner. Methods: A Jaszczak phantom and a NEMA PET body phantom were filled with ¹⁸F-FDG, ⁶⁸Ga-HCl, or ⁶⁴Cu-HCl, and PET/CT scans were performed on a Siemens Biograph Vision. Acquired images were analyzed regarding spatial resolution and image quality (recovery coefficients (RC), coefficient of variation within the background, contrast recovery coefficient (CRC), contrast–noise ratio (CNR), and relative count error in the lung insert). Data were compared between scans with different nuclides. Results: We found that image quality was comparable between ¹⁸F-FDG and ⁶⁴Cu-HCl PET/CT measurements featuring similar maximal endpoint energies of the positrons. In comparison, RC, CRC, and CNR were degraded in ⁶⁸Ga-HCl data despite similar count rates. In particular, the two smallest spheres of 10 mm and 13 mm diameter revealed lower RC, CRC, and CNR values. The spatial resolution was similar between ¹⁸F-FDG and ⁶⁴Cu-HCl but up to 18% and 23% worse compared with PET/CT images of the NEMA PET body phantom filled with ⁶⁸Ga-HCl. Conclusions: The positron energy of the PET nuclide influences the spatial resolution and image quality of a digital PET/CT scan. The image quality and spatial resolution of ⁶⁸Ga-HCl PET/CT images were worse than those of ¹⁸F-FDG or ⁶⁴Cu-HCl despite similar count rates.

99mTc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, 99mTc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a 99mTc-labeled HYNIC-DAPI compound with that of 99mTc pertechnetate (99mTcO4−). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by 99mTcO4− (0.51), and the number of DSBs increased fivefold in the 99mTc-HYNIC-DAPI-treated sample compared with the 99mTcO4− treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the 99mTcO4– treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the 99mTc-HYNIC-DAPI-treated samples. These results indicated that 99mTc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the 99mTc-labeled compound with DNA. In contrast to these results, 99mTcO4− induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of 99mTc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by approximately 10-fold in terms of inducing DSBs.

Radiomercury 197mHg and 197Hg, henceforth referred to as 197(m)Hg, is a promising theranostic radionuclide endowed with properties that allow diagnostic and therapeutic applications. The aim of this work was to investigate the capabilities of 197(m)Hg for nuclear medicine imaging. Therefore measurements were performed by using a Philips BrightView SPECT camera. Furthermore, Monte Carlo simulations using the GATE software were performed to theoretically explore the imaging contribution from the various gamma and X-ray emissions from 197(m)Hg for a commercial clinical camera with low-energy high-resolution (LEHR) and high-energy general-purpose (HEGP) collimators. We estimated the spatial resolution by using a four-quadrant bar phantom, and we evaluated the planar and tomographic images from an abdominal phantom containing three cylindrical sources of 197(m)Hg solution. A good accordance between measurements and simulations was found for planar and SPECT imaging. Simulations allowed the decomposition of the detected energy spectrum into photon origins. Measurements and simulations for the bar phantom revealed that for the LEHR collimator, the 6-mm pattern could be resolved, whereas for the HEGP collimator, the resolution is about 10 mm. Furthermore, we found that no significant image distortion results from high-energy photons when using the LEHR collimator. We demonstrated the imaging capabilities of 197(m)Hg which is essential both for diagnostic applications and to determine the in vivo biodistribution for dose calculations in therapeutic applications.

The application of ²²⁵Ac (half-life T_1/2 = 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 E_α = 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.

The aim of the study was to increase the uptake of the SSTR2-targeted radioligand Lu-177-DOTATATE using the DNA methyltransferase inhibitor (DNMTi) 5-aza-2′-deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The HEKsst₂ and PC3 cells were incubated with variable concentrations of 5-aza-dC and VPA to investigate the uptake of Lu-177-DOTATATE. Cell survival, subsequent to external X-rays (0.6 or 1.2 Gy) and a 24 h incubation with 57.5 or 136 kBq/mL Lu-177-DOTATATE, was investigated via colony formation assay to examine the effect of the epidrugs. In the case of stimulated HEKsst₂ cells, the uptake of Lu-177-DOTATATE increased by a factor of 28 in comparison to the unstimulated cells. Further, stimulated HEKsst₂ cells demonstrated lower survival fractions (factor 4). The survival fractions of the PC3 cells remained almost unchanged. VPA and 5-aza-dC did not induce changes to the intrinsic radiosensitivity of the cells after X-ray irradiation. Clear stimulatory effects on HEKsst₂ cells were demonstrated by increased cell uptake of the radioligand and enhanced SST2 receptor quantity. In conclusion, the investigated approach is suitable to stimulate the somatostatin receptor expression and thus the uptake of Lu-177-DOTATATE, enabling a more efficient treatment for patients with poor response to peptide radionuclide therapy (PRRT).