This study aimed to investigate the dynamics, pharmacokinetic characteristics, and radiation dosimetry of [68Ga]Ga-OncoACP3-DOTA, a novel prostatic acid phosphatase (ACP3)-targeted radioligand, in patients with metastatic castration-resistant prostate cancer. Methods: Seven patients with metastatic castration-resistant prostate cancer had dynamic or multiple-time-point PET/CT scans after intravenous injection of [68Ga]Ga-OncoACP3-DOTA available. Five patients had early dynamic scans over the thorax, and 6 had dynamic whole-body PET scans during the first hour after injection. Five patients underwent an additional late-time-point whole-body PET scan (median, 3.2 h postinjection). SUVs for volumes of interest were determined for normal organs and metastases, and uptake dynamics and tumor-to-background ratios were calculated. Pharmacokinetic modeling was performed for multiple compartment models and evaluated in accordance with the Akaike information criterion. Dosimetry calculations were performed using MIRDfit and MIRDcalc, with time-integrated activity coefficients scaled to the International Commission on Radiological Protection 133 Adult Male Reference Phantom. Results: [68Ga]Ga-OncoACP3-DOTA displayed declining uptake in most organs, except for organs involved in excretion, and stable uptake was observed only in the prostate. Dual renal and hepatobiliary excretion was noted. Declining blood kinetics were well-fitted by a triexponential function. Metastases showed an increase in uptake from early to late time points, with intensely increasing tumor-to-background ratios. Pharmacokinetic modeling indicated that a 2-tissue compartment model with irreversible binding was most appropriate for describing metastatic uptake. Bone and lymph node metastases exhibited significant differences in K 1 and K i values. The mean effective dose was 0.0192 mSv/MBq, resulting in an effective dose of 3.50 mSv for a standard injection of 2.5 MBq/kg. The highest absorbed doses were observed in bone marrow (0.0913 mGy/MBq), kidneys (0.0657 mGy/MBq), and liver (0.0563 mGy/MBq), whereas salivary glands showed a negligible absorbed dose (0.0135 mGy/MBq). Conclusion: [68Ga]Ga-OncoACP3-DOTA demonstrated favorable pharmacokinetics with increasing tumor uptake and tumor-to-background ratios at later time points, suggesting potential benefits for delayed imaging, especially with high-sensitive PET systems or radiolabeling with isotopes with longer half-lives. The dosimetry profile was favorable, with a lower effective dose compared with many prostate-specific membrane antigen-targeted radiopharmaceuticals and negligible salivary gland uptake, potentially reducing side effects during radiopharmaceutical therapy. Future studies are warranted to evaluate its clinical value.

Positron emission tomography (PET) using fibroblast activation protein inhibitors (FAPI) has emerged as a robust imaging tool for solid tumours. The novel ligand [68Ga]BED003 (formerly known as [68Ga]Ga-OncoFAP-DOTAGA) has demonstrated very high affinity for the fibroblast activation protein and favourable biodistribution. This study aimed to assess the in vivo distribution of [68Ga]BED003 across a spectrum of solid tumours as a potential prerequisite for radioligand therapy. In this retrospective analysis, [68Ga]BED003 PET/CT or PET/MRI of 157 patients with 19 different solid malignancies were retrospectively analysed. A spherical volume of interest (VOI) was placed over the primary tumour, the most intense lymph node and distant metastases that were evaluated as at least likely malignant in the written reports, and the maximum standardized uptake value (SUVmax) was derived. Liver and blood pool background mean SUV (SUVmean) were assessed using standardised VOIs. Tumour-to-background ratios (TBRmax) were calculated as the ratio of SUVmax to background SUVmean. SUVmax and TBRmax values of primary tumours, lymph node, and distant metastases were compared using Wilcoxon rank-sum and signed-rank tests, as appropriate. Overall, 115 primary tumours, 70 lymph node metastases, and 116 distant metastases were analysed, yielding median SUVmax of 16.6, 12.3, and 11.9, respectively. No significant difference in SUVmax or TBRmax were observed between lymph node and distant metastases (all P > 0.05). In contrast, primary tumours demonstrated significantly higher uptake than lymph node and distant metastases (all P < 0.001), except for liver TBRmax when comparing primary tumours with lymph node metastases (P > 0.05). Across all 301 lesions, the median SUVmax, liver TBRmax and blood pool TBRmax was 14.7 (range, 4.2–35.9), 21.6 (range, 4.2–62.8) and 11.1 (range, 3.0–33.4), respectively. The highest median SUVmax and TBRmax (both) in cohorts with > 5 lesions were found in medullary thyroid, oesophageal, ovarian, cervical, breast, colorectal, and hepatocellular cancers. [68Ga]BED003-PET demonstrated consistently high uptake across diverse solid malignancies, supporting its potential role as a tool for multi-cancer diagnostic imaging and patient selection for FAP-targeted radioligand therapy.

Prostate-specific membrane antigen (PSMA)-targeted theranostic agents have transformed prostate cancer (PC) management, but their performance is limited by variable PSMA expression and off-target uptake. We investigates the first-in-human positron emission tomography (PET) imaging of prostatic acid phosphatase (ACP3), a novel and highly specific PC target, using the radioligand [68Ga]Ga-OncoACP3-DOTA. We analyzed and matched [68Ga]Ga-OncoACP3-DOTA and [18F]PSMA-1007 PET scans in a cohort of 25 patients with PC. We compared the biodistribution and tumor uptake of the two tracers using the Wilcoxon rank-sum test and compared their performance. Superiority was defined as >10% more lesions detected or >50% higher lesional maximum standardized uptake value (SUVmax). [68Ga]Ga-OncoACP3-DOTA showed low background uptake, including in the salivary glands and kidneys, with a significant difference from the high [18F]PSMA-1007 uptake in these organs (p < 0.002). Overall, SUVmax in localized or metastatic PC did not significantly differ between the two tracers. Better [68Ga]Ga-OncoACP3-DOTA performance was observed in 11/25 matched scan pairs, and better [18F]PSMA-1007 performance in eight of 25 pairs. [68Ga]Ga-OncoACP3-DOTA changed therapeutic management in three of six patients with biochemical recurrence, and in two of 12 patients with known metastases. Although the retrospective comparison is potentially biased, the intense and reliable tumor uptake and the low off-target activity of OncoACP3-DOTA provide a strong rationale for future exploration in trials on PET imaging and radioligand therapy with β- and α-particle emitters.

Ziel/Aim Dynamic contrast-enhanced (DCE) MRI allows to estimate perfusion parameters in-vivo based on quantification of the dynamic tissue and arterial blood contrast agent (CA) concentrations (arterial input function, AIF) and pharmacokinetic modeling. However, validation of MR CA concentration estimates is rarely performed. In this study, we validated DCE-MRI with co-injected radioactive contrast agent analogues and by mass spectrometry.

Kinetic modelling of dynamic PET typically requires knowledge of the arterial radiotracer concentration (arterial input function, AIF). Its accurate determination is very difficult in mice. AIF measurements in an extracorporeal shunt can be performed; however, this introduces catheter dispersion. We propose a framework for extracorporeal dispersion correction and validated it by comparison to invasively determined intracorporeal AIFs using implanted microprobes.The response of an extracorporeal radiation detector to radioactivity boxcar functions, characterised by a convolution-based dispersion model, gave best fits using double-gamma variate and single-gamma variate kernels compared to mono-exponential kernels for the investigated range of flow rates. Parametric deconvolution with the optimal kernels was performed on 9 mice that were injected with a bolus of 39 ± 25 MBq [18F]F-PSMA-1007 after application of an extracorporeal circulation for three different flow rates in order to correct for dispersion. Comparison with synchronous implantation of microprobes for invasive aortic AIF recordings showed favourable correspondence, with no significant difference in terms of area-under-curve after 300 s and 5000 s. One-tissue and two-tissue compartment model simulations were performed to investigate differences in kinetic parameters between intra- and extracorporeally measured AIFs. Results of the modelling study revealed kinetic parameters close to the chosen simulated values in all compartment models.The high correspondence of simultaneously intra- and extracorporeally determined AIFs and resulting model parameters establishes a feasible framework for extracorporeal dispersion correction. This should allow more precise and accurate kinetic modelling in small animal experiments.

We studied the antitumor efficacy of a combination of 177Lu-labeled radioligand therapeutics targeting the fibroblast activation protein (FAP) (OncoFAP and BiOncoFAP) with the antibody-cytokine fusion protein L19-interleukin 2 (L19-IL2) providing targeted delivery of interleukin 2 to tumors. Methods: The biodistribution of 177Lu-OncoFAP and 177Lu-BiOncoFAP at different molar amounts (3 vs. 250 nmol/kg) of injected ligand was studied via SPECT/CT in mice bearing subcutaneous HT-1080.hFAP tumors, and self-absorbed tumor and organ doses were calculated. The in vivo anticancer effect of 5 MBq of the radiolabeled preparations was evaluated as monotherapy or in combination with L19-IL2 in subcutaneously implanted HT-1080.hFAP and SK-RC-52.hFAP tumors. Tumor samples from animals treated with 177Lu-BiOncoFAP, L19-IL2, or both were analyzed by mass spectrometry-based proteomics to identify therapeutic signatures on cellular and stromal markers of cancer and on immunomodulatory targets. Results: 177Lu-BiOncoFAP led to a significantly higher self-absorbed dose in FAP-positive tumors (0.293 +/- 0.123 Gy/MBq) than did 177Lu-OncoFAP (0.157 +/- 0.047 Gy/MBq, P 5 0.01) and demonstrated favorable tumorto-organ ratios at high molar amounts of injected ligand. Administration of L19-IL2 or 177Lu-BiOncoFAP as single agents led to cancer cures in only a limited number of treated animals. In 177Lu-BiOncoFAP-plus- L19-IL2 combination therapy, complete remissions were observed in all injected mice (7/7 complete remissions for the HT-1080.hFAP model, and 4/4 complete remissions for the SK-RC-52.hFAP model), suggesting therapeutic synergy. Proteomic studies revealed a mechanism of action based on the activation of natural killer cells, with a significant enhancement of the expression of granzymes and perforin 1 in the tumor microenvironment after combination treatment. Conclusion: The combination of OncoFAP-based radioligand therapeutics with concurrent targeting of interleukin 2 shows synergistic anticancer effects in the treatment of FAP-positive tumors. This experimental finding should be corroborated by future clinical studies.

Ziel/Aim Attenuation correction of fixed coil elements in hybrid PET-MRI systems is usually performed using vendor-provided attenuation maps. However, in the case of third-party coils, users may have to implement their own templates. We here report this for a dedicated breast coil array, whose geometrically different prototype was previously investigated [1].

Ziel/Aim The dynamic arterial radiotracer concentration (arterial input function, AIF) is difficult to determine accurately in PET of mice. We already successfully performed AIF measurements using a pump-driven extracorporeal shunt [1]. We here investigate AIF measurements using the same setup without the pump, driven by mouse blood pressure alone, as the usage of a pump may not be possible in some cases, e.g. in preclinical PET-MRI.

Therapy with 90Y-labeled fibroblast activation protein inhibitors (90Y-FAPIs) was recently introduced as a novel treatment concept for patients with solid tumors. Lesion and organ-at-risk dosimetry is part of assessing treatment efficacy and safety and requires reliable quantifi-cation of tissue uptake. As 90Y quantification is limited by the low inter-nal positron-electron pair conversion rate, the increased effective sensitivity of digital silicon photomultiplier-based PET/CT systems might increase quantification accuracy and, consequently, allow for dosimetry in 90Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in 90Y-FAPI radionu-clide therapy using a digital PET/CT system. Methods: Two tumor phantoms were filled with 90Y solution using different sphere activity concentrations and a constant signal-to-background ratio of 40. The minimum detectable activity concentration was determined, and its dependence on acquisition time (15 vs. 30 min per bed position) and smoothing levels (all-pass vs. 5-mm gaussian filter) was investigated. Quantification accuracy was evaluated at various activity concentra-tions to estimate the minimum quantifiable activity concentration using contour-based and oversized volume-of-interest-based quantification approaches. A 620% deviation range between image-derived and true activity concentrations was regarded as acceptable. Tumor dosimetry for 3 patients treated with 90Y-FAPI is presented to project the phantom results to clinical scenarios. Results: For a lesion size of 40 mm and a clinical acquisition time of 15 min, both minimum detectable and mini-mum quantifiable activity concentrations were 0.12 MBq/mL. For lesion sizes of greater than or equal to 30 mm, accurate quantification was feasible for detectable lesions. Only for the smallest 10-mm sphere, the minimum detectable and minimum quantifiable activity concentrations differ substantially (0.43 vs. 1.97 MBq/mL). No notable differences between the 2 quantification approaches were observed. For the inves-tigated tumors, absorbed dose estimates with reliable accuracy were achievable. Conclusion: For lesion sizes and activity concentrations that are expected to be observed in patients treated with 90Y-FAPI, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate the efficacy and safety of 90Y-FAPI therapy.

Ziel/Aim PET using O-15-H2O enables insights which brain regions are involved in speech processing. We simulated low-count studies to determine the minimal dose at which diagnostic significance can be maintained.

Backgrounds Elastic motion correction in PET has been shown to increase image quality and quantitative measurements of PET datasets affected by respiratory motion. However, little is known on the impact of respiratory motion correction on clinical image evaluation in oncologic PET. This study evaluated the impact of motion correction on expert readers’ lymph node assessment of lung cancer patients. Methods Forty-three patients undergoing F-18-FDG PET/CT for the staging of suspected lung cancer were included. Three different PET reconstructions were investigated: non-motion-corrected (“static”), belt gating-based motion-corrected (“BG-MC”) and data-driven gating-based motion-corrected (“DDG-MC”). Assessment was conducted independently by two nuclear medicine specialists blinded to the reconstruction method on a six-point scale s ranging from “certainly negative” (1) to “certainly positive” (6). Differences in s between reconstruction methods, accounting for variation caused by readers, were assessed by nonparametric regression analysis of longitudinal data. From s , a dichotomous score for N1, N2, and N3 (“negative,” “positive”) and a subjective certainty score were derived. SUV and metabolic tumor volumes (MTV) were compared between reconstruction methods. Results BG-MC resulted in higher scores for N1 compared to static ( p = 0.001), whereas DDG-MC resulted in higher scores for N2 compared to static ( p = 0.016). Motion correction resulted in the migration of N1 from tumor free to metastatic on the dichotomized score, consensually for both readers, in 3/43 cases and in 2 cases for N2. SUV was significantly higher for motion-corrected PET, while MTV was significantly lower (all p < 0.003). No significant differences in the certainty scores were noted. Conclusions PET motion correction resulted in significantly higher lymph node assessment scores of expert readers. Significant effects on quantitative PET parameters were seen; however, subjective reader certainty was not improved.

Zielsetzung Die PET-Atembewegungskorrektur verbessert die subjektive Bildqualität und quantitative PET-Messwerte. Es ist jedoch nur unzureichend bekannt, ob dies auch zu einem veränderten TNM-Staging führt. Unsere Studie untersucht den Einfluss der PET-Bewegungskorrektur auf das Lymphknoten-Staging bei Lungenkrebspatienten.

Ziel/Aim Pharmacokinetic modeling (PKM) of dynamic PET allows to absolutely quantify molecular features in vivo. Exact dynamic arterial radiotracer concentrations (arterial input function, AIF) are a prerequisite, but difficult to determine in mice. Measurements in an extracorporeal shunt can be made (1); however, dispersion effects are introduced in this approach. We here propose a novel approach to describe these effects.

Ziel/Aim Image-derived measurements of the dynamic arterial blood concentration (arterial input function, AIF) for pharmacokinetic modeling (PKM) are challenging for both PET and MRI in mice. Alternatively, an extracorporeal circulation approach can be used [1]. We evaluated the quantitative precision of extracorporeally measured AIFs of MRI contrast agent (CA) and its radioactive analog by dual recordings and compared dispersion effects in two different vascular access ways.

The determination of the glomerular filtration rate (GFR) is decisive for a variety of clinical issues, for example, to monitor the renal function in radionuclide therapy patients. Renal scintigraphy using glomerularly filtered tracers allows combined acquisition of renograms and GFR estimation but requires repeated blood sampling for several hours. In contrast, dynamic PET imaging using the glomerularly filtered tracer [68Ga]Ga-DOTA bears the potential to non-invasively estimate the GFR by compartmental kinetic modelling. Here, we report the, to our knowledge, first comparison of human renal dynamic [68Ga]Ga-DOTA PET imaging in comparison to renal scintigraphy and compare PET-derived to serum creatinine-derived GFR measurements. Dynamic [68Ga]Ga-DOTA PET data were acquired for 30 min immediately after tracer injection in 12 patients. PET and renal scintigraphy images were visually interpreted in a consensus read by three nuclear medicine physicians. The functional renal cortex was segmented to obtain time-activity curves. The arterial input function was estimated from the PET signal in the abdominal aorta. Single-compartmental tracer kinetic modelling was performed to calculate the GFR using complete 30-min (GFRPET-30) and reduced 15-min PET data sets (GFRPET-15) to evaluate whether a shorter acquisition time is sufficient for an accurate GFR estimation. A modified approach excluding minutes 2 to 10 was applied to reduce urinary spill-over effects. Serum creatinine-derived GFRCKD (CKD-EPI-formula) was used as reference standard. PET image interpretation revealed the same findings as conventional scintigraphy (2/12 patients with both- and 1/12 patients with right-sided urinary obstruction). Model fit functions were substantially improved for the modified approach to exclude spill-over. Depending on the modelling approach, GFRCKD and both GFRPET-30 and GFRPET-15 were well correlated with interclass correlation coefficients (ICCs) from 0.74 to 0.80 and Pearson’s correlation coefficients (PCCs) from 0.74 to 0.81. For a subgroup of patients with undisturbed urinary efflux (n = 9), correlations were good to excellent (ICCs from 0.82 to 0.95 and PCCs from 0.83 to 0.95). Overall, GFRPET-30 and GFRPET-15 were excellently correlated (ICCs from 0.96 to 0.99 and PCCs from 0.96 to 0.99). Renal [68Ga]Ga-DOTA PET can be a suitable alternative to conventional scintigraphy. Visual assessment of PET images and conventional renograms revealed comparable results. GFR values derived by non-invasive single-compartmental-modelling of PET data show a good correlation to serum creatinine-derived GFR values. In patients with undisturbed urinary efflux, the correlation was excellent. Dynamic PET data acquisition for 15 min is sufficient for visual evaluation and GFR derivation.

Background Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course. Purpose Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach. Methods Hybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake. Results A characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = −0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004). Conclusions Segmental FDG uptake—reflecting myocardial metabolic activity—is higher in the LV free wall of BMD patients—possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.