Prostate-specific membrane antigen (PSMA), a type II glycoprotein, is highly expressed in almost all prostate cancers. By playing such a universal role in the disease, PSMA provides a target for diagnostic imaging of prostate cancer using positron emission tomography/computed tomography (PET/CT). The PSMA-targeting ligand Glu-NH-CO-NH-Lys-(Ahx)-HBED-CC (DKFZ-PSMA-11) has superior imaging properties and allows for highly-specific complexation of the generator-based radioisotope Gallium-68 (⁶⁸Ga). However, only module-based radiolabeling procedures are currently available. This study intended to develop a single vial kit solution to radiolabel buffered DKFZ-PSMA-11 with ⁶⁸Ga. A ⁶⁸Ge/⁶⁸Ga-generator was utilized to yield ⁶⁸GaCl₃ and major aspects of the kit development were assessed, such as radiolabeling performance, quality assurance, and stability. The final product was injected into patients with prostate cancer for PET/CT imaging and the kit performance was evaluated on the basis of the expected biodistribution, lesion detection, and dose optimization. Kits containing 5 nmol DKFZ-PSMA-11 showed rapid, quantitative ⁶⁸Ga-complexation and all quality measurements met the release criteria for human application. The increased precursor content did not compromise the ability of ⁶⁸Ga-DKFZ-PSMA-11 PET/CT to detect primary prostate cancer and its advanced lymphatic- and metastatic lesions. The ⁶⁸Ga-DKFZ-PSMA-11 kit is a robust, ready-to-use diagnostic agent in prostate cancer with high diagnostic performance.

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi⁸, Met(O₂)¹¹]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO₂ generator matrix as well as preliminary results on the adaptability to produce [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi⁸, Met(O₂)¹¹]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP mixed with [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP. [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP providing sufficient activity for 1–2 human doses. The resultant formulation of [⁶⁸Ga]Ga-/[²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi⁸, Met(O₂)¹¹]SP—a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [⁶⁸Ga]Ga-DOTA-[Thi⁸, Met(O₂)¹¹]SP and [²¹³Bi]Bi-DOTA-[Thi⁸, Met(O₂)¹¹]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.

Ribwort plantain (Plantago lanceolata L.) is a common weed in the winter rainfall region of South Africa. This weed is widespread across vineyards, orchards, and roadsides in the region. The weed has already evolved resistance to glyphosate and paraquat; however, the mechanism of paraquat resistance has not been documented. This study aimed to investigate the resistance mechanisms in this resistant (R) biotype. Dose–response trials conducted with R biotypes from the Robertson area reconfirmed paraquat resistance. Dose–response trials established that the paraquat rate causing 50% mortality (LD₅₀) for the R biotype is three times greater than for the susceptible (S) biotype. To find out how paraquat affected the photosynthetic performance of P. lanceolata, the quantum yield of photosystem II was measured. The photosystem reaction centres of the R biotype recovered 24 h after paraquat treatment. To evaluate paraquat transport in the plant cell, selective transport inhibitors were applied. Plantago lanceolata (S) biotypes had the highest electrolyte leakage after paraquat treatment. A combined radio/UV-HPLC was used for the separation and identification of paraquat and its metabolites. Paraquat degradation was not observed, indicating that metabolism was not a resistance mechanism within the R biotype. To assess leaf absorption and translocation, [¹⁴C]-labelled paraquat was applied to fully expanded leaves. There were no significant differences in paraquat absorption. However, paraquat translocation differed significantly across the R and S biotypes, indicating that non-target site resistance through reduced paraquat translocation was the main mechanism of resistance in the R biotype. As the resistance of weed species to post-emergence herbicides continues to increase, achieving sustainable weed management necessitates the implementation of diversified weed control strategies.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.