Publikationen

The incidence of osteoporosis and osteoporotic fragility fractures is increasing due to demographic changes. Therefore, early diagnosis is desirable in order to preserve bone health and prevent low-trauma fractures. Opportunistic screening for osteoporosis by frequently performed computed tomography scans could offer a potential solution. Cranial computed tomography is often performed in potential high-risk patients for osteoporosis due to frequent falls in older ages. The aim of this study was to examine the potential value of opportunistic osteoporosis screening by cranial computed tomography-derived Hounsfield units in the overall clinical context, including sustained major osteoporotic fractures, pre-existing diseases and lifestyle factors.

Manual segmentation of organs from PET/CT images is a time-consuming and highly operator-dependent task. Open software solutions are now available to automatically segment all major anatomical structures in CT images.

The liver-brain axis regulates metabolic homeostasis, with glucose metabolism playing a key role. Liver dysfunction, such as fibrosis, may impact brain metabolism and consequently, brain function. Positron emission tomography (PET) imaging provides a non-invasive approach to study glucose metabolism in both organs. A recent longitudinal PET/CT study utilizing 2-deoxy-2-[F]-fluoro-d-glucose ([F]FDG) amongst other radiotracers revealed significant metabolic changes in the liver in a mouse model of liver fibrosis. Here, we retrospectively analyzed those data to quantify potential associated changes in brain glucose metabolism.

To evaluate the diagnostic performance of Ga-DOTATATE PET, contrast-enhanced CT, combined DOTATATE PET/CT, and MRI in detecting neuroendocrine liver metastases on a per-lesion basis and to assess the added value of diagnostic contrast-enhanced CT to PET interpretation as well as influence of lesion size.

Combined PET/CT imaging provides critical insights into both anatomic and molecular processes, yet traditional single-tracer approaches limit multidimensional disease phenotyping; to address this, we developed the PET Unified Multitracer Alignment (PUMA) framework-an open-source, postprocessing tool that multiplexes serial PET/CT scans for comprehensive voxelwise tissue characterization. PUMA utilizes artificial intelligence-based CT segmentation from multiorgan objective segmentation to generate multilabel maps of 24 body regions, guiding a 2-step registration: affine alignment followed by symmetric diffeomorphic registration. Tracer images are then normalized and assigned to red-green-blue channels for simultaneous visualization of up to 3 tracers. The framework was evaluated on longitudinal PET/CT scans from 114 subjects across multiple centers and vendors. Rigid, affine, and deformable registration methods were compared for optimal coregistration. Performance was assessed using the Dice similarity coefficient for organ alignment and absolute percentage differences in organ intensity and tumor SUV Deformable registration consistently achieved superior alignment, with Dice similarity coefficient values exceeding 0.90 in 60% of organs while maintaining organ intensity differences below 3%; similarly, SUV differences for tumors were minimal at 1.6% ± 0.9%, confirming that PUMA preserves quantitative PET data while enabling robust spatial multiplexing. PUMA provides a vendor-independent solution for postacquisition multiplexing of serial PET/CT images, integrating complementary tracer data voxelwise into a composite image without modifying clinical protocols. This enhances multidimensional disease phenotyping and supports better diagnostic and therapeutic decisions using serial multitracer PET/CT imaging.

For patients with oligometastatic nodal recurrence after radical prostatectomy (RP), salvage radiotherapy is a valuable curative second-line treatment option. However, few clinical data on the impact of PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) is available. In order to contribute further clinical data on the outcome of patients treated with sENRT following RP, we analysed the rates of biochemical recurrence-free survival (BRFS) and distant metastasis-free survival (DMFS) as well as potential predictive markers for optimised patient selection.

Recently, multifunctional platinum(IV) complexes designed as prodrugs for the anticancer drug carboplatin and the iron chelator deferoxamine (DFO), each featuring a DFO unit at one axial position and either hemisuccinate or acetate at the other, were developed. As these compounds contain DFO, they hold the potential to be radiolabelled with gallium-68 for molecular imaging and to be recognized by microorganisms, which can utilise DFO as a siderophore-based iron source being taken up by specific siderophore transporters (SITs). Combining this recognition mechanism with a cytotoxic carboplatin core, these compounds could potentially lead to specific antimicrobial activity, particularly against Aspergillus fumigatus (AFU), which causes systemic infections and expresses relevant SITs. The two complexes were radiolabelled with gallium-68 and evaluated for radiochemical purity and protein binding, exhibiting quantitative Ga-labeling yields with high radiochemical purity and stability in human serum as well as low protein binding. In vitro uptake assays in AFU and AFU mutants lacking SITs were performed as well as MIC assays for assessment of antifungal activity in comparison to DFO and carboplatin alone. Complexes were also evaluated in in vivo assays including stability studies in healthy mice as well as biodistribution studies and PET imaging in a rat pulmonary aspergillosis model, revealing favourable pharmacokinetics with rapid distribution and a renal excretion pattern with pronounced accumulation in AFU infected lung tissue. However, rapid metabolism of the complexes was observed already 5 min p.i. in serum and urine samples. Overall, this study demonstrates the potential of carboplatin-based Pt(IV)-DFO conjugates for application in infection theranostics.

[Ga]Ga-DOTATOC is widely used in PET imaging of neuroendocrine tumors (NETs) due to its high affinity for somatostatin receptors. Given the short physical half-life of gallium-68 (~68 min), rapid, reproducible, and GMP-compliant synthesis is essential for clinical application. An optimized cassette-based automated synthesis protocol was developed using a commercial cassette. Improvements included direct generator elution into the reactor without pre-purification, use of a SepPak C18 Plus Light cartridge for purification, replacement of HEPES with 0.3 M sodium acetate buffer (final pH ~3.8), and implementation of a non-vented sterile filter enabling automated pressure-hold integrity testing. Across all batches, the synthesis yielded [Ga]Ga-DOTATOC with high radiochemical purity (> 97%) and reproducible decay-corrected radiochemical yields up to 88.3 ± 0.6%. Total synthesis time was approximately 13 min. The final product remained stable for at least 3 h post-synthesis. The use of acetate buffer eliminated the need for HEPES-specific testing, streamlining the workflow. Automated filter testing improved GMP-compliant documentation and reduced radiation exposure for personnel. This optimized, cassette-based synthesis protocol enables fast, high-yield, and GMP-compliant production of [Ga]Ga-DOTATOC. It supports clinical theranostic workflows by ensuring product quality, process standardization, and regulatory compliance.

18F-Fluorodeoxyglucose-Positron Emission Tomography - Computed Tomography (18FDG-PET-CT) is commonly used for baseline clinical staging in cervical cancer. In this study, we assessed the prognostic value of standardised PET-CT parameters for the overall survival (OS) of patients treated with definitive chemoradiotherapy (CRT), or radiotherapy (RT) with subsequent brachytherapy (BT).

Current machine learning-based (ML) models usually attempt to utilize all available patient data to predict patient outcomes while ignoring the associated cost and time for data acquisition. The purpose of this study is to create a multi-stage ML model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Two hundred eighteen patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6 ± 1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0 ± 11.8, and LVEF of 27.7 ± 11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without significantly sacrificing performance.

Hippocampal injury is linked to cognitive impairment and cardiac events in patients with heart failure with reduced ejection fraction. However, the predictive value of hippocampal metabolic activity (HMA) for sudden cardiac death (SCD) and the underlying mechanisms remain unclear. This study aimed to evaluate the independent and incremental predictive value of HMA over myocardial scar for SCD-related events in patients with heart failure with reduced ejection fraction and to explore the potential mechanism.

: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [Tc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. : CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed by Western blotting. : studies showed similar target-specific binding and internalization of [In]In-RM2 and [Tc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, imaging showed negligible tumor uptake in xenografts of the transduced cell lines. analysis indicated a loss of the respective biomarkers in the xenografts. : Although the technical feasibility of a dual-tracer SPECT imaging approach using In and Tc has been demonstrated, the potential of [Tc]Tc-PSMA-I&S and [In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The / experiments indicated that results from an model may not necessarily be successfully transferred to an setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches.

Targeting dynamic inflammatory-fibrotic pathways post-myocardial infarction (MI) is essential for exploring novel biomarkers to improve healing and attenuate adverse left ventricular (LV) remodeling. This study aimed to investigate the spatiotemporal dynamic pattern of immune inflammation and fibroblast activation and to map the proteomic profile of different regions over time after acute MI (AMI).

: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and Tc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. : A total of 44 patients with diagnosed ATTR-CM, who underwent Tc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). : The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO and DPD retention index (r = -0.355, = 0.018) as well as between peak VO at anaerobic threshold with DPD retention index (r = -0.391, = 0.009). Interestingly, there was no strong correlation between VE/VCO slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO, specifically for NT-proBNP (r = -0.530, < 0.001) and Troponin T (r = -0.431, < 0.001). : In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM.

[Tc]Tc-GSA, an albumin-based glycoprotein, is routinely used in Japan to measure the asialoglycoprotein receptor (ASGR) density via single photon emission tomography. Here we describe the development of Ga-labeled peptide-based alternatives. Peptides were assembled on a solid support using a fragment coupling strategy. Glycosylation was carried out via a click chemistry approach resulting in a set of three peptides with increasing amounts of d-galactose ( = 3, 6, and 9) as well as one glycopeptide bearing nine -acetylgalactosamine residues. Ga-labeling of all compounds could be achieved in high radiochemical yields (>95%). Radiotracers exhibited high hydrophilicity, good metabolic stability in human serum and protein binding between 12 and 22%. The IC values improved in the series tri-, hexa-, and nonamer with an IC of 50 ± 30 pM for the latter one. In analogy, the biodistribution studies revealed increased liver uptake in the series of [Ga]Ga- (9.4 ± 2.0% ID/g, 30 min p.i.), [Ga]Ga- (55.5 ± 7.4% ID/g, 30 min p.i.), and [Ga]Ga- (79.6 ± 8.0% ID/g, 30 min p.i.). [Ga]Ga-NODAGA-GalNAc-NonaLysan reached comparable liver uptake to [Ga]Ga-, but showed higher accumulation in nontarget organs. The impressive imaging properties of [Ga]Ga- were also confirmed by the PET/MR imaging studies in mice. Hence, [Ga]Ga- represents a new PET radiopharmaceutical with even better imaging properties than [Tc]Tc-GSA.

Dopamine transporter imaging is routinely used in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) diagnosis. While [C]CFT PET is prevalent in Asia with a large APS database, Europe relies on [I]FP-CIT SPECT with limited APS data. Our aim was to develop a deep learning-based method to convert [C]CFT PET images to [I]FP-CIT SPECT images, facilitating multicenter studies and overcoming data scarcity to promote Artificial Intelligence (AI) advancements.

To evaluate right ventricular (RV) uptake measured by quantitative [Tc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA).

Clinical parameters measured from gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) have value in predicting cardiac resynchronization therapy (CRT) patient outcomes, but still show limitations. The purpose of this study is to combine clinical variables, features from electrocardiogram (ECG), and parameters from assessment of cardiac function with polar maps from gated SPECT MPI through deep learning (DL) to predict CRT response. A total of 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6-month follow-up. A DL model was constructed by combining a pre-trained VGG16 model and a multilayer perceptron. Two modalities of data were input to the model: polar map images from SPECT MPI and tabular data from clinical features, ECG parameters, and SPECT-MPI-derived parameters. Gradient-weighted class activation mapping (Grad-CAM) was applied to the VGG16 model to provide explainability for the polar maps. For comparison, four machine learning (ML) models were trained using only the tabular features. Modeling was performed on 218 patients who underwent CRT implantation with a response rate of 55.5% (n = 121). The DL model demonstrated average AUC (0.83), accuracy (0.73), sensitivity (0.76), and specificity (0.69) surpassing ML models and guideline criteria. Guideline recommendations achieved accuracy (0.53), sensitivity (0.75), and specificity (0.26). The DL model trended towards improvement over the ML models, showcasing the additional predictive benefit of utilizing SPECT MPI polar maps. Incorporating additional patient data directly in the form of medical imagery can improve CRT response prediction.

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Radiopharmaceutical therapy (RPT) is entering a new era of personalization, driven by advances in molecular imaging, radiopharmaceutical development, and a growing body of clinical evidence linking absorbed dose to treatment outcomes. Although external-beam radiotherapy has long integrated dosimetry into standard practice, RPT historically relied on fixed radiopharmaceutical activities and absorbed dose-effect relationships adapted from external-beam radiotherapy, often without accounting for the unique pharmacokinetics, absorbed dose rate dynamics, and biologic responses of systemically administered radiopharmaceuticals. As RPT expands into earlier disease stages, at which patients have longer life expectancies and better performance status, the role of dosimetry in optimizing treatment is becoming increasingly evident. However, despite growing recognition of its benefits, the implementation of dosimetry in clinical practice remains limited, partly because of a self-reinforcing cycle in which the lack of routine dosimetry limits clinical evidence, which in turn hinders its broader adoption. Breaking this cycle is essential to advancing RPT and ensuring that evaluation of dosimetry is based on clinical merit rather than logistic constraints. This article examines the current landscape of RPT dosimetry, highlighting key challenges and opportunities from a European perspective and aiming to foster a more factual and constructive discussion on the topic. We discuss the fundamental differences between dosimetry-driven treatment planning and posttherapy absorbed dose verification, emphasizing the latter as a practical entry point for clinical adoption. We underscore the need for harmonized standards, improved imaging resolution, and tailored absorbed dose-effect relationships that reflect the heterogeneity of RPT delivery and the complexity of tumor and organ responses. The paper also addresses regulatory, infrastructural, and resource barriers to RPT dosimetry implementation and highlights ongoing European initiatives to strengthen frameworks, enhance stakeholder collaboration, and integrate absorbed dose biomarkers into authorization processes and clinical decision-making. By rethinking dosimetry and promoting standardized, evidence-based approaches, the field can advance beyond fixed-activity protocols toward truly individualized RPT. However, achieving clinically feasible integration of dosimetry into routine practice requires structured efforts to generate high-quality clinical evidence and improve accessibility. Ultimately, reliable, patient-centered dosimetry has the potential to enhance therapeutic efficacy, manage toxicity more effectively, and support the long-term evolution of RPT as a cornerstone of precision oncology.

There are no established treatment options for patients with meningioma recurring after surgery and radiotherapy. Somatostatin receptor type 2 (SSTR2) is highly expressed in meningiomas, and SSTR2-targeting radionuclide therapy with [Lu]Lu-DOTATATE has shown potential activity in the treatment of meningioma in uncontrolled and small studies. EORTC-2334-BTG (LUMEN-1, NCT06326190) is a randomized, multicenter, phase II trial in patients with recurrent World Health Organization (WHO) grade 1, 2, or 3 meningioma. In total, 136 patients will be randomized in a 2:1 ratio to [Lu]Lu-DOTATATE (≤4 doses of 7.4 GBq given every 4 wk) or local standard of care (hydroxyurea, bevacizumab, sunitinib, octreotide, everolimus, or observation). The main eligibility criteria include age 18 y or older; neuropathologically confirmed meningioma of WHO grade 1, 2, or 3; WHO performance score of 0-2; measurable disease on MRI (≥10 × 10 mm); radiologically documented progression of any existing tumor (growth > 25% or new lesions) or appearance of new lesions within the last 2 y; SSTR positivity by PET imaging (SUV > 2.3); at least 1 prior surgery and at least 1 line of radiotherapy; and no prior systemic therapy. The primary efficacy endpoint is locally assessed progression-free survival according to Response Assessment in Neuro-Oncology MRI meningioma criteria, and secondary endpoints include radiologic response rate, overall survival, safety, health-related quality of life, and neurologic function. The trial protocol includes a comprehensive exploratory translational research program with dosimetry and imaging-based and tissue-based investigations. LUMEN-1 was activated in March 2025 and will enroll patients in 35 sites in 10 countries across Europe, with primary endpoint collection planned after 2 y and study completion after 5 y. To our knowledge, EORTC-2334-BTG (LUMEN-1, NCT06326190) is the first prospective randomized trial investigating the efficacy of [Lu]Lu-DOTATATE in patients with recurrent meningioma.

High-grade meningiomas have high recurrence rates and limited prognosis. Radioligand therapies are approved in extracranial malignancies, but their value in brain tumours including meningiomas is unclear, as data on target expression is scarce.

Since its inception in 2012, the Nuclear Medicine Global Initiative (NMGI) of the Society of Nuclear Medicine and Molecular Imaging has played an important role in addressing significant challenges in the field of nuclear medicine and molecular imaging. The first 3 projects were dedicated to standardizing pediatric nuclear medicine practices, addressing the global challenges of radionuclide access and availability, and assessing the educational and training initiatives on theranostics across the globe. These efforts aimed to advance human health, foster worldwide educational collaboration, and standardize procedural guidelines to enhance quality and safety in nuclear medicine practice. In its latest project, NMGI aimed to develop a unified nomenclature for systemic radionuclide therapy in nuclear medicine, addressing the diverse terminology currently used. An online survey was distributed to NMGI member organizations, drawing participation from various geographical locations and disciplines. The survey anonymously collected responses from physicians, physicists, scientists, radiopharmacists, radiopharmaceutical scientists, dosimetrists, technologists, and nurse managers, totaling 240 responses from 30 countries. Findings revealed a prevailing use of the term targeted radionuclide therapy for radionuclide therapy, with 52% of respondents expressing a preference for this term. In contrast, approximately 37% favored "radiopharmaceutical therapy," whereas 11% favored "molecular radionuclide therapy." Other key terms under the umbrella of targeted radionuclide therapy were also discussed to achieve a consensus on terminology. NMGI efforts to standardize terminology in this dynamic and fluid field should improve communication within the field, better reflect the technology used, enable comparison of results, and ultimately lead to improved patient outcomes.

Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice.

Radiolabelled minigastrin (MG) analogues targeting the cholecystokinin-2 receptor (CCK2R) have proven to be a promising approach for peptide receptor radionuclide therapy (PRRT). In this study, we report on the radiopharmaceutical development and standardization of the preparation of [Lu]Lu-DOTA-MGS5 using an automated synthesis module. Furthermore, we present the preclinical tests required to move forward towards a first therapeutic clinical trial as well as preliminary clinical dosimetry data.

First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise a family of five G protein-coupled receptors that are widely distributed across the human body and are expressed by various tumor types. The growing understanding of their clinical potential led to the introduction of both cold and radiolabeled somatostatin analogs (SSAs), which have revolutionized the management of several cancers, especially neuroendocrine tumors. As a direct consequence, advances in peptide receptor radionuclide therapy (PRRT) over the last 30 years led to the approval of Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Theoretically, any cancer patients whose tumors express SSTR, as demonstrated in vivo through SSTR-based molecular imaging, could be candidates for PRRT, especially those with limited treatment options. However, evidence on the efficacy of PRRT in non-GEPNET SSTR-expressing tumors is limited, and mainly derived from small retrospective studies. Given the limited therapeutic options for advanced/metastatic patients, there is a clear need for randomized trials to formally approve PRRT with SSAs for patients who may benefit from this treatment, particularly in certain types of neuroendocrine neoplasms such as lung carcinoids, paragangliomas, and meningiomas, where high rates of disease control (up to 80%) can be achieved. In addition, emerging evidence supports the potential of combination therapies, alpha emitters, and non-SSTR-based radionuclide therapy in tumors beyond GEPNET. This review aims to provide a comprehensive overview of PRRT's role in cancers beyond GEPNET, exploring new possibilities and future directions for most SSTR highly expressing tumors.

 High-dose epidermal radionuclide therapy using a nonsealed Re (Rhenium) resin is an alternative treatment option for nonmelanoma skin cancer. In this case study, we present the possible use of this therapy in a patient with multiple actinic keratosis (AK), which is a precancer of the skin.  A 55-year-old male was presented in our department with multiple AK, located on the cheek, temporal, and frontal area, with 1, 1, 2.1, and 2.5 cm surface. Applied activity was 80, 80, 167, and 168 MBq Re with a target absorbed dose for each lesion 35 Gy at 1 mm. The treatment was well tolerated.  At 17 months' follow-up, all treated area showed complete remission. There were no side effects, except mild focal hypopigmentation.  This case demonstrates the high potential of epidermal radionuclide therapy with a nonsealed Re as a noninvasive, effective, and well-tolerated therapy option for patients with multiple AK, when surgery is difficult to perform or not recommended of other reasons.

This systematic review aims to examine the safety and efficacy of fibroblast activation protein inhibitor (FAPI) radioligand therapy (RLT) for various epithelial neoplasms. PubMed, Web of Science, and Scopus databases were searched up to Jan 4, 2025, for studies involving FAPI RLT in various cancers. Data extraction focused on exploring safety and efficacy of FAPI RLT. Overall, 27 studies involving a total of 144 patients who received FAPI RLT were included in this systematic review. [Lu]Lu-FAPI was employed in 21 studies, with 225 cycles administered to 95 patients at a median dose of 6.8 GBq/cycle. Six non-randomized clinical investigations using [Lu]Lu-FAPI reported disease control rates ranging from 18.2% to 83.3%. Only three studies documented a cumulative total of six patients who experienced grade 3 or 4 toxicity post [Lu]Lu-FAPI RLT. Of 16 case reports utilizing [Lu]Lu-FAPI, nine achieved disease control across various cancer types, with no reported adverse events. Four studies employed [Y]Y-FAPI, totaling 103 cycles in 42 patients at a median dose of 6.7 GBq/cycle. Three non-randomized clinical investigations reported disease control rates of 50% to 82%, with two studies documenting eight high-grade toxicity events. Furthermore, a successful administration of [Y]Y-FAPI was employed in a single reported case involving multiple primary neoplasms with no reported adverse events. However, the patient did not achieve disease control post [Y]Y-FAPI. A cohort study utilized 53 [Bi]Bi-FAPI-46 injections following a fractionated dose regimen in six cancer patients, achieving a 33.3% disease control rate without reported adverse events. One case report described dual radionuclide therapy using two cycles with a cumulative 20 GBq [Sm]Sm-FAPI and a third 8 GBq [Y]Y-FAPI cycle in a lung cancer patient, resulting in stable disease for eight months. FAPI RLT is a promising and safe therapeutic agent in oncology, with potential benefits achieved on short-term basis. However, its long-term efficacy and safety require further research with larger, controlled studies, considering the currently observed variations in patient populations, cancer types, and methodologies within reviewed studies.

Radioligand therapy (RLT) has garnered significant attention due to the recent emergence of innovative and effective theranostic agents, which showed promising therapeutic and prognostic results in various cancers. Moreover, understanding the interaction between different types of radiation and biological tissues is essential for optimizing therapeutic interventions These concepts directly apply to clinical RLTs and play a crucial role in determining the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that aids in estimating patient-specific absorbed doses in both tumors and normal organs. Dosimetry in RLT is an area of active investigation, as our current understanding of the relationship between absorbed dose and tissue damage is primarily derived from external-beam radiation therapy. Further research is necessary to comprehensively comprehend this relationship in the context of RLTs. In the present review, we present a thorough examination of the involvement of Lu/Ac radioisotopes in the induction of direct and indirect DNA damage, as well as their influence on the initiation of DNA repair mechanisms in cancer cells of neuroendocrine tumors and metastatic prostate cancer. Current data indicate that high-energy α-emitter radioisotopes can directly impact DNA structure by causing ionization, leading to the formation of ionized atoms or molecules. This ionization process predominantly leads to the formation of irreparable and intricate double-strand breaks (DSBs). On the other hand, the majority of DNA damage caused by β-emitter radioisotopes is indirect, as it involves the production of free radicals and subsequent chemical reactions. Beta particles themselves can also physically interact with the DNA molecule, resulting in single-strand breaks (SSBs) and potentially reversible DSBs.