Publikationen

Prostate-specific membrane antigen (PSMA) PET has become a highly accurate imaging modality for prostate cancer (PCa), demonstrating superior diagnostic performance. However, substantial variability exists in imaging protocols beyond standard time-point acquisition, and the clinical value of these variations remains unclear. The aim of this study is to systematically review and compare PSMA PET protocols in PCa patients, focusing on detection rates and potential advantages, using extracted data from published studies. A systematic review was conducted in PubMed and Scopus through August 2025 for studies evaluating various PSMA PET protocols, including early, delayed, diuretic-aided, and hybrid/multiphasic imaging. Eligible studies included original research comparing these approaches with standard imaging. Ninety-seven studies (n = 8,428 patients) were included. Early imaging improved visualization of prostate bed and peri‑bladder lesions, increasing detection of local recurrence by 9-12% and enhancing tumor-to-background ratios up to fourfold, particularly in biochemical recurrence (BCR) with low PSA levels. Late imaging (2-4 h post-injection) consistently increased lesion contrast, detected additional lesions (up to 38.5%), and altered staging in up to 66.7% of cases, especially in equivocal or low-PSA settings. Diuretic-aided protocols reduced urinary artifacts, improved diagnostic confidence (63% to 91%), and revealed previously obscured lesions. Hybrid and multiphasic protocols demonstrated incremental gains in sensitivity and specificity, particularly in selected BCR populations, though benefits were context-dependent. Additional PSMA PET acquisitions provide complementary, scenario-specific diagnostic advantages but yield modest overall incremental benefit. Their judicious use, particularly in low-PSA BCR, equivocal findings, and pelvic disease, is recommended.

[F]FDG functional PET (fPET) enables investigation of dynamics in glucose metabolism occurring within seconds. However, the physiological mechanisms supporting rapid metabolic changes necessitate further attention to allow accurate interpretation. This work highlights candidate mechanisms driving [F]FDG signal changes at high temporal resolution, offering complementary insights to existing interpretations. At rest, metabolic demands are closely matched by glucose supply across the blood-brain barrier (BBB), regulated by glucose transporter 1 (GLUT1). During neuronal activation, glucose transport and phosphorylation by hexokinase are elevated to meet increased energy requirements. Simulations indicate that rapid [F]FDG signal increases are primarily driven by BBB transport, with subsequent increases in hexokinase activity. Mechanisms supporting increased BBB transport include elevated glucose concentration gradient towards the brain and changes in GLUT1 intrinsic properties, but only minor effects of blood flow. Conversely, moment-to-moment fluctuations in [F]FDG used for metabolic connectivity, reflect temporally synchronized supply, mediated jointly by blood flow and BBB transport. We emphasize that the coupling between BBB transport and metabolism underpin the [F]FDG fPET signal. Considering alterations of GLUT1 and subsequent metabolism in numerous brain disorders, stimulation-induced energy demands and metabolic connectivity represent a promising opportunity to investigate the underlying pathophysiological processes.

Monoaminergic neurotransmitters help regulate the interplay between the central nervous system and the immune system. Aberrant monoaminergic functional connectivity is presumably involved in MS-related fatigue, but mechanisms remain unclear.

Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with [F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to [Lu]Lu-PSMA-I&T in a cohort of patients with [F]FDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated.

Fibroblast activation plays a key role in plaque instability and coronary artery disease (CAD) progression. In-stent restenosis (ISR) remains a major complication after percutaneous coronary intervention (PCI), increasing the risk of major adverse cardiovascular events (MACEs). This study primarily aimed to investigate whether coronary [¹⁸F]AlF-NOTA-FAPI-04 uptake is associated with major adverse cardiovascular events (MACEs) in symptomatic post-PCI patients, and secondarily to explore its ability to differentiate ISR from in-stent non-restenosis (ISnR) and to evaluate longitudinal changes under lipid-lowering therapy.

Reward processing is essential to human brain function, with dopamine signalling in the nucleus accumbens (NAcc) as a key element. The monetary incentive delay task is widely studied with functional magnetic resonance imaging (fMRI), measuring indirect hemodynamic changes. Functional positron emission tomography (fPET) with 6-[¹⁸F]FDOPA directly quantifies dopamine synthesis, enabling dynamic assessment during task performance within a single scan. We investigated the reliability of 6-[¹⁸F]FDOPA fPET and blood oxygenation level dependent (BOLD) fMRI during a modified monetary incentive delay task in 25 (10 female; age 24.6 ± 6.1 years) healthy participants across two PET/MRI sessions. Intraclass correlation coefficients and coefficients of variance were computed for BOLD beta estimates and striatal dopamine synthesis (Ki) at 30 s and 2 s resolutions in the caudate, putamen and NAcc. 6-[¹⁸F]FDOPA Ki estimates showed fair to good reliability in the NAcc and putamen at rest (ICC = 0.47-0.66), fair reliability during the win condition in the caudate and putamen (ICC = 0.46-0.57), but poor reliability across the loss condition in all regions (ICC = 0.11-0.39). Conversely, fMRI beta showed good reliability in the NAcc during feedback and in the caudate during feedback loss (ICC = 0.61-0.67), but fair reliability elsewhere (ICC = 0.4-0.46) except for poor reliability in the caudate during cue loss (ICC = 0.26). These findings indicate that both methods achieve comparable reliability but in different target areas, with the molecular specificity of fPET offering dynamic assessment of dopaminergic function. Clinicaltrials.gov Identifier: NCT06675851. EudraCT Number: 2019-004880-33.

MRI is recommended for men with clinical suspicion of significant prostate cancer. Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of clinically significant prostate cancer, and a high incidence of clinically insignificant prostate cancer. We aimed to investigate whether gallium-68 ([Ga]Ga)-prostate-specific membrane antigen (PSMA)-11 PET-CT could reduce the number of people requiring prostate biopsy and limit biopsy to targeted cores, without compromising clinically significant prostate cancer diagnosis.

The aim of this study was to investigate the limits of diagnostics and therapy planning for patients with prostate cancer using non-time-of-flight F/Ga-PSMA PET/MRI under clinically challenging imaging conditions with small lesion sizes and low uptake. Lesion detectability and quantification accuracy were evaluated for different acquisition and reconstruction parameters in a systematic phantom study and subsequent on patient data.

This study focuses on evaluating how SubtlePET™, an artificial intelligence (AI)-based image enhancement algorithm, produced PET/CT images compare against EARL Standard-2 harmonized images, and to assess its impact on quantitative accuracy and workflow in a clinical setting.

Non-melanoma skin cancer (NMSC), represents the most common malignancy in fair-skinned populations and constitutes a growing public health burden. Although surgery remains the standard of care, a significant proportion of patients are poor surgical candidates due to age, comorbidities, tumor location or personal preference, highlighting the need for effective non-surgical alternatives.

Quantitative single-photon emission computed tomography (SPECT) with 99m Tc-3,3-diphosphono-1,2 propanodicarboxylicacid ([ 99m Tc]Tc-DPD) is a cornerstone in the noninvasive diagnostic workup of amyloid transthyretin-related cardiomyopathy (ATTR-CM). As diagnosis is often suspected after transthoracic echocardiography (TTE), this study aims to explore the correlations between global and regional quantitative [ 99m Tc]Tc-DPD SPECT results and TTE findings in patients with suspected ATTR-CM.

To date, there are no clear recommendations for the treatment of a clinically inconspicuous neck (cN0) in sinonasal squamous cell carcinoma. Elective neck dissection or neck irradiation appears too aggressive given the relatively low occult metastasis rates. However, the development of neck lymph node metastases is significantly associated with worse survival, therefore patients at relevant risk need to be identified. The aim of this trial was to evaluate feasibility and safety of sentinel node biopsy for sinonasal squamous cell carcinoma.

Scintigraphy using Tc-labeled bone-seeking tracers is a cornerstone in the non-invasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). However, planar imaging alone, particularly in patients with Perugini score 1, often lacks diagnostic specificity. This study evaluates the incremental diagnostic value of quantitative SPECT/CT at 90 min post-injection (p.i.) when added to standard planar imaging at 60 and 180 min.

Cardiac transthyretin amyloidosis (ATTR-CM) is a progressive myocardial disease ultimately leading to heart failure. Standard diagnostic workup includes Tc-DPD scintigraphy performed after 2.5-3 h. The purpose of this study is to compare early (1 h after injection) to late imaging of Tc-DPD scintigraphy and SPECT for the detection of ATTR-CM. Early imaging could improve patient comfort and examination efficiency.

Internal dosimetry in radiopharmaceutical therapy (RPT) traditionally prioritizes methodological optimization driven by physical dose accuracy. However, even recommended multiple-time-point (MTP) dosimetry remains subject to uncertainties related to limited sampling schedules, pharmacokinetic, and curve-fitting modeling assumptions. In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [Lu]Lu-PSMA-617 RPT, we explored an outcome-driven dosimetry optimization strategy by comparing MTP and single-time-point (STP) dosimetry, and identifying optimal time-points (TPs) for Hänscheid approximation based on therapy outcomes.

PURPOSE: We herein present the results of the second survey on SPECT and PET myocardial perfusion imaging (MPI) in Austria, Germany, and Switzerland in 2024. METHODS: A questionnaire was sent to facilities practicing nuclear medicine. RESULTS: Data from 12 Austrian (10,689 SPECT), 198 German (128,707 SPECT), and 16 Swiss departments (11,593 MPI (2,911 SPECT; 8,682 PET)) were analysed. In Austria and Germany, the PET MPI numbers were negligible and not considered. In Austria 50%, in Germany 69%, and in Switzerland 69% of the facilities reported stable or increasing numbers of examinations compared to the 2021 survey. Ambulatory care cardiologists represented the major referral group (46-71%). Most stress tests were performed pharmacologically (57-96%). In SPECT imaging, the one-day protocol was predominant in Switzerland (77%), while the two-day protocol was used in Austria (41%) and Germany (49%). The primary camera systems used were hybrid SPECT-CT systems in Austria (75%) and Switzerland (100%), and SPECT cameras (without CT) in Germany (56%). Attenuation correction was regularly performed in Switzerland (100%), followed by Austria (74%), and Germany (35%). Both gated SPECT and perfusion scoring were frequently applied (gated SPECT 82-99%; perfusion scoring 82-88%). CONCLUSIONS: This second joint survey for 2024 confirms positive trends in MPI imaging in all three countries, albeit with differences. The results document a high level of guideline conformity. The situation in Switzerland is exceptional due to the widespread use of PET-MPI. Switzerland also leads in terms of camera equipment and attenuation correction followed by Austria and Germany.

The Cardiovascular and Interventional Radiological Society of Europe (CIRSE) conducted an international survey on the real-life application of transarterial radioembolization (TARE). This sub-analysis of the complete survey evaluates intercontinental disparities in TARE practices.

In recent decades, there has been marked worldwide growth in diagnostic testing for coronary artery disease (CAD), with several common imaging modalities exposing patients to ionizing radiation.

Progressive supranuclear palsy (PSP) causes rapid motor decline and severe dopaminergic dysfunction. While uric acid (UA) may act as a neuroprotective antioxidant in some neurodegenerative disorders (like Parkinson’s disease), its role in PSP remains unclear. This study evaluated the relationship between serum UA levels, measured cross-sectionally and longitudinally, and striatal dopamine transporter binding in PSP. A total of 33 PSP patients with repeated pre-[123I]FP-CIT SPECT UA measurements, along with 30 healthy control individuals and 30 patients with Alzheimer’s disease (AD), were retrospectively analyzed. Group and sex effects were analyzed with t tests and ANOVA. Effects of mean UA and longitudinal UA trajectories on FP-CIT SPECT binding in PSP were modeled using linear mixed-effects models and regressed against binding in four regions (caudate and putamen), separated into more-affected and less-affected side for both sexes. A Bayesian two-stage measurement-error model provided sensitivity analysis. UA was significantly lower in PSP (4.98 mg/dl) and AD (4.69 mg/dl) compared to healthy controls (5.71 mg/dL; p = 0.001). Sex had a significant effect on UA (F(1, 89) = 9.38, p = 0.003, partial η2 = 0.10), however, this effect was significant only in PSP (p< 0.001). Within PSP, UA–[123I]FP-CIT SPECT correlations were weak and nonsignificant, and neither UA intercept nor slope predicted [123I]FP-CIT SPECT binding (all p > 0.7). Bayesian estimates corroborated the absence of a credible relationship. In the present cohort, serum UA is reduced in PSP, primarily in females, but neither mean levels nor longitudinal changes are related to striatal [123I]FP-CIT SPECT binding, suggesting no clear association with dopaminergic degeneration in PSP, without precluding a potential role of uric acid at other disease stages.

: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. : N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. : In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca and Mg had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). : A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required.

Peptide receptor radionuclide therapy (PRRT) has established itself as a pivotal component in the management of advanced, somatostatin receptor (SSTR)-positive neuroendocrine tumours (NETs). The NETTER-1 phase III trial demonstrated that [Lu]Lu-DOTATATE significantly prolongs progression-free survival (PFS) and improves quality of life in patients with midgut NETs refractory to somatostatin analogues, leading to regulatory approval by both EMA (2017) and FDA (2018). The recent NETTER-2 phase III trial further extended these findings by supporting the first-line use of PRRT in Grade 2 and 3 gastroentero-pancreatic (GEP)-NETs (Ki-67 ≥ 10 ≤ 55%). Beyond standard β-emitting therapy, several developments are reshaping the field: the clinical adoption of SSTR antagonists such as radiolabelled JR-11 and LM3, targeted α-particle-emitting therapies (Ac, Pb, Bi) for resistant disease, and rational combination strategies with chemotherapy, DNA-repair inhibitors, and immunotherapy. Parallel innovation in radiopharmaceutical chemistry has yielded new peptide ligands, including cholecystokinin-2 receptor (CCK2R)-targeted compounds such as DOTA-MGS5, which show promise for rare NETs such as medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC). This review summarises clinical evidence, translational advances, and future perspectives for PRRT as a cornerstone of precision nuclear oncology. Emphasis is placed on expanding indications, integrating α-emitters, improving safety and dosimetry, and developing novel theragnostic ligands that enable personalised treatment strategies for NETs patients.

Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with [F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to [Lu]Lu-PSMA-I&T in a cohort of patients with [F]FDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated.

The aim of this study was to investigate the limits of diagnostics and therapy planning for patients with prostate cancer using non-time-of-flight F/Ga-PSMA PET/MRI under clinically challenging imaging conditions with small lesion sizes and low uptake. Lesion detectability and quantification accuracy were evaluated for different acquisition and reconstruction parameters in a systematic phantom study and subsequent on patient data.

Recent data demonstrate that one possibility for increasing Peptide Receptor Radionuclide Therapy (PRRT) results lies in the combination of PRRT with chemotherapy. This study aimed to evaluate response and outcome in [F]FDG-positive metastatic neuroendocrine tumor (mNET) patients treated with PRRT alone or in combination with temozolomide (TEM) plus/minus capecitabine (CAP).

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.

Continuation of effective and well-tolerated systemic treatment is often performed in care for metastatic castration-resistant prostate cancer. Likewise, continued administration of [Lu]Lu-PSMA radiopharmaceutical therapy beyond the approved number of cycles holds promising potential to enhance therapeutic efficacy. Rechallenge therapy involves readministration of [Lu]Lu-PSMA cycles after a break, whereas extended therapy continues treatment beyond the standard 6 cycles without interruption. Both approaches aim to improve disease control and prolong survival in patients with metastatic castration-resistant prostate cancer. However, practices vary: some clinicians continue treatment in patients with early favorable responses, whereas others recommend pausing therapy after significant prostate-specific antigen declines, even after a few cycles. In this narrative review, we show that safety profiles for continued [Lu]Lu-PSMA radiopharmaceutical therapy are generally favorable, and most adverse events are mild to moderate in severity. Hematotoxicity, particularly anemia and thrombocytopenia, is the most significant concern, with few patients experiencing high-grade adverse events. In addition, cumulative irradiation, particularly during extended therapy, necessitates careful monitoring of hematologic and renal function. Biochemical responses to rechallenge and extended [Lu]Lu-PSMA therapy are promising, with at least 50% reductions in prostate-specific antigen levels observed in a significant proportion of highly selected patients. Moreover, survival outcomes are encouraging, showing the extension of overall and progression-free survival beyond the known data for standard therapy. Despite these advances, challenges remain in optimizing patient selection, managing cumulative toxicities, and harmonizing treatment protocols. In addition, variability in trial designs, influenced by international regulatory differences, limits the current evidence and necessitates consideration of each treatment approach within its regulatory context. Prospective studies are needed to refine therapeutic strategies, implement consistent clinical and imaging response criteria, and identify predictive biomarkers to improve both efficacy and safety.

: Peptide receptor radionuclide therapy (PRRT) is an established treatment for neuroendocrine tumors (NETs), enabling targeted radiation delivery via radiolabeled peptides. Small cell lung cancer (SCLC) remains a major therapeutic challenge due to its aggressive nature and poor prognosis. Despite advances, relapse rates are high and effective therapies are limited. We previously demonstrated the diagnostic potential of the cholecystokinin-2 receptor (CCK2R)-targeting minigastrin analog [Ga]Ga-DOTA-MGS5 in PET/CT imaging of different NETs. Building on this, we developed and evaluated [Lu]Lu-DOTA-MGS5 as a therapeutic PRRT agent. : Preclinical studies investigating the receptor-mediated cellular internalization and intracellular distribution over time in A431 cells with and without CCK2R expression were performed using the fluorescent tracer ATTO-488-MGS5. Short- and long-term cytotoxic effects of [Lu]Lu-DOTA-MGS5 were evaluated on the same cell line using trypan blue exclusion and clonogenic survival assays. CCK2R expression was assessed by immunohistochemistry in 42 SCLC tissue specimens. In addition, the first PRRT with [Lu]Lu-DOTA-MGS5 was conducted in a patient with extensive disease SCLC (ED-SCLC) after confirming CCK2R-positive uptake in [Ga]Ga-DOTA-MGS5 PET/CT. : Rapid binding and internalization into A431-CCK2R cells, with progressive accumulation in intracellular compartments, was observed for ATTO-488-MGS5. Short-term irradiation effects of [Lu]Lu-DOTA-MGS5 were comparable for 4 h and 24 h incubation and were between the effects obtained with 2 and 4 Gy of external beam radiotherapy (EBRT). Clonogenic survival of A431-CCK2R cells incubated with increasing activity of [Lu]Lu-DOTA-MGS5 decreased in a dose-dependent manner. Immunohistochemistry on SCLC specimens confirmed moderate to high CCK2R expression in 16 out of 42 SCLC samples. In the first patient with SCLC treated with four cycles of [Lu]Lu-DOTA-MGS5 with a total activity of 17.2 GBq, an improvement in clinical symptoms was observed. : The preclinical and clinical results confirm the feasibility of [Lu]Lu-DOTA-MGS5 PRRT in patients with SCLC and support further clinical studies investigating the therapeutic value and clinical applicability of this new CCK2R-targeted theranostic approach in larger patient cohorts.

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.

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.

Non-melanoma skin cancer (NMSC), represents the most common malignancy in fair-skinned populations and constitutes a growing public health burden. Although surgery remains the standard of care, a significant proportion of patients are poor surgical candidates due to age, comorbidities, tumor location or personal preference, highlighting the need for effective non-surgical alternatives.