The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress. A particular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g., for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes as well as their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.

Background: The analysis aimed to compare the radiotracers [⁶⁸Ga]-Ga-PSMA-11 and [¹⁸F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. Methods: A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [⁶⁸Ga]-Ga-PSMA-11- and [¹⁸F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. Results: Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [¹⁸F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [¹⁸F]-F-PSMA-1007 and [⁶⁸Ga]-Ga-PSMA-11 in the SUV_max locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [¹⁸F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [¹⁸F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). Conclusion: In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [¹⁸F]-F-PSMA-1007 and [⁶⁸Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [¹⁸F]-F-PSMA-1007.

Inflammation and alterations in essential protein structures in the brain might also change the cellular distribution in the cerebrospinal fluid (CSF).

Purpose: ^203/212Pb is a promising theranostic isotope pair for targeted alpha therapy (TAT) of neuroendocrine tumors (NET). VMT-α-NET is a novel SSTR2 targeting peptide that can be labeled with both isotopes. The aim of this work was to perform first clinical investigations of [^203/212Pb]Pb-VMT-α-NET regarding imaging, biokinetics, tolerability and response. Methods: 12 patients (9 m/3 w; mean age 71, range 60–84) with progressive metastatic GEP-NET grade 1–3 received diagnostic imaging with [²⁰³Pb]Pb-VMT-α-NET (4.9 MBq/kg bw) up to 24 h p.i. (whole body & SPECT/CT) and, if eligible, a single dose of [²¹²Pb]Pb-VMT-α-NET therapy (1.2 MBq/kg bw) after exhaustion of all current therapies (including [¹⁷⁷Lu]Lu- & [²²⁵Ac]Ac-DOTATATE), and post-treatment imaging with [²¹²Pb]Pb-VMT-α-NET up to 24 h p.i. (whole body & SPECT/CT). Clinical and laboratory parameters were monitored. A visual and quantitative comparison was made with [⁶⁸ Ga]Ga-DOTATATE PET scans before and 3 months after therapy. Results: No high-grade adverse effects were observed in all patients evaluated with [²⁰³Pb]Pb-VMT-α-NET. All patients showed an initial high, but lesion-dependent heterogeneous intratumoral accumulation, comparable to [⁶⁸ Ga]Ga-DOTATATE PET. Treatment with [²¹²Pb]Pb-VMT-α-NET was also well tolerated by all patients without high-grade or serious adverse side effects. Post-therapeutic PET scans and tumor marker controls showed stable findings in all patients up to 3 months after treatment. Conclusion: Imaging with [²⁰³Pb]Pb-VMT-α-NET followed by a single dose of [²¹²Pb]Pb-VMT-α-NET appears to be well tolerated with promising efficacy, even in a heterogenous and heavily pretreated patient population. Further studies are warranted to examine tolerability and efficacy over multiple treatment cycles in larger patient populations.

(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.

Vascular graft/endograft infection (VGEI) is a serious complication after aortic surgery. This study investigates VGEI and patient characteristics, PET/CT quantification before surgical or conservative management of VGEI and post-intervention outcomes in order to identify patients who might benefit from such a procedure. PET standard uptake values (SUV) were quantitatively assessed and compared to a non-VGEI cohort. The primary endpoints were in-hospital mortality and aortic reintervention-free survival at six months. Ninety-three patients (75% male, 65 ± 10 years, 82% operated) were included. The initial operation was mainly for aneurysm (67.7%: 31% EVAR, 12% TEVAR, 57% open aortic repair). Thirty-two patients presented with fistulae. PET SUV_TLR (target-to-liver ratio) showed 94% sensitivity and 89% specificity. Replacement included silver-coated Dacron (21.3%), pericardium (61.3%) and femoral vein (17.3%), yet the material did not influence the overall survival (p = 0.745). In-hospital mortality did not differ between operative and conservative treatment (19.7% vs. 17.6%, p = 0.84). At six months, 50% of the operated cohort survived without aortic reintervention. Short- and midterm morbidity and mortality remained high after aortic graft removal. Neither preoperative characteristics nor the material used for reconstruction influenced the overall survival, and, with limitations, both the in-hospital and midterm survival were similar between the surgically and conservatively managed patients.