(1) Background: In neuroendocrine tumors (NETs), somatostatin receptor subtype 2 is highly expressed, which can be targeted by a radioactive ligand such as [¹⁷⁷Lu]Lu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴,-tetraacetic acid-[Tyr³,Thr⁸]-octreotide (¹⁷⁷Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing ^203/212Pb-PSC-PEG₂-TOC (PSC-TOC). The molar activity (A_M) can play a crucial role in tumor uptake, especially in receptor-mediated uptake, such as in NETs. Therefore, an investigation of the influence of different molar activities of ^203/212Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of ^203/212Pb-PSC-TOC was performed with 50 µg of precursor in a NaAc/AcOH buffer at pH 5.3–5.5 within 15–45 min at 95° C. Cell uptake was studied in AR42 J, HEK293 sst2, and ZR75-1 cells. (3) Results: ^203/212Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with A_M ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of ²⁰³Pb-PSC-TOC (A_M = 38 MBq/nmol) was highest in AR42 J (17.9%), moderate in HEK293 sstr (9.1%) and lowest in ZR75-1 (0.6%). Cell uptake increased with the level of A_M. (4) Conclusions: A moderate A_M of 15–40 MBq/nmol showed the highest cell uptake. No uptake limitation was found in the first 24–48 h. Further escalation experiments with even higher A_M should be performed in the future. It was shown that A_M plays an important role because of its direct dependence on the cellular uptake levels, possibly due to less receptor saturation with non-radioactive ligands at higher A_M.

Background/Objectives: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are highly sensitive clinical imaging modalities, frequently employed in conjunction with magnetic resonance imaging (MRI) or computed tomography (CT) for diagnosing a wide range of disorders. Efficient and robust radiolabeling methods are needed to accommodate the increasing demand for PET and SPECT tracer development. Copper-mediated radiohalogenation (CMRH) reactions enable rapid late-stage preparation of radiolabeled arenes, yet synthetic challenges and radiolabeling precursors’ instability can limit the applications of CMRH approaches. Methods: A series of aryl-boronic acids were converted into their corresponding aryl-boronic acid 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] and aryl-boronic acid 1,1,2,2-tetrapropylethylene glycol esters [ArB(Ppin)s] as stable and versatile precursor building blocks for radiolabeling via CMRH. General protocols for the preparation of ¹⁸F-labeled and ¹²³I-labeled arenes utilizing CMRH of these substrates were developed and applied. The radiochemical conversions (RCC) were determined by radio-(U)HPLC. Results: Both ArB(Epin)s and ArB(Ppin)s-based radiolabeling precursors were prepared in a one-step synthesis with chemical yields of 49–99%. Radiolabeling of the aryl-boronic esters with fluorine-18 or iodine-123 via CMRH furnished the corresponding radiolabeled arenes with RCC of 7–99% and 10–99%, respectively. Notably, a radiohalogenated prosthetic group containing a vinyl sulfone motif was obtained with an activity yield (AY) of 18 ± 3%, and applied towards the preparation of two clinically relevant PET tracers. Conclusions: This approach enables the synthesis of stable radiolabeling precursors and thus provides increased versatility in the application of CMRH, thereby supporting the development of novel PET and SPECT radiotracers.

Clinically used imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are highly sensitive non-invasive imaging modalities utilized in combination with magnetic resonance imaging (MRI) or computed tomography (CT) for the diagnosis of a multitude of disorders. Efficient and robust radiolabeling methods are needed to accommodate for the increasing demand for PET and SPECT tracer development. Copper-mediated radiohalogenation (CMRH) reactions have been reported for the rapid late-stage preparation of radiolabeled arenes, yet synthetic challenges and instability of corresponding radiolabeling precursors can limit the applications of CMRH radiolabeling approaches. In this work, a general protocol for the preparation of 18F-labeled and 123I-labeled arenes applying CMRH of stable aryl boronate substrates is reported. The method utilizes aryl boronic acid 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] and aryl boronic acid 1,1,2,2-tetrapropylethylene glycol esters [ArB(Ppin)s] as stable and versatile precursor building blocks for radiolabeling via CMRH. Both ArB(Epin)s and ArB(Ppin)s based radiolabeling precursors were prepared in a one-step synthesis from the corresponding aryl boronic acids with chemical yields of 49-99%. Radiolabeling of the aryl boronic esters with fluorine-18 or iodine-123 via CMRH furnished the corresponding radiolabeled arenes with RCC of 7-99% and 10-99%, respectively. Notably, a radiohalogenated prosthetic group containing a vinyl sulfone motif was obtained with an activity yield (AY) of 18 ± 3%, and applied towards the preparation of two clinically-relevant PET tracers.

Background: Energy delivered at different wavelengths causes different types of damage to DNA. Methods: PC-3, FaDu, 4T1 and B16-F10 cells were irradiated with different wavelengths of ultraviolet light (UVA/UVC) and ionizing radiation (X-ray). Furthermore, different photosensitizers (ortho-iodo-Hoechst33258/psoralen/trioxsalen) were tested for their amplifying effect. Survival fraction and damage analysis using the $\mathrm{\gamma }$H2A.X assay (double-strand breaks) and the ELISA assay (cyclobutane pyrimidine dimers) were compared. Results: The PC-3 cells were found to be the most sensitive cells to the treatment strategies used. FaDu and PC-3 showed a strong sensitivity to UVA. Analysis of the damage showed that the cell lines exhibited different sensitivities. Conclusions: Thus, an enhancing effect of photosensitizers (PS) in combination with UVA could be demonstrated in some cases. However, this is cell- and dose-dependent.