EJNMMI Research最新文献

Background: Isotopic renography is pivotal for assessing upper urinary tract obstruction and provides renal functional parameters. New 3D-CZT cameras offer enhanced sensitivity and innovative full SPECT protocols that need to be validated on phantoms. Current renal phantoms are often complex and suitable for 2D imaging. Using a new printed 3D renal phantom, we compared planar and full SPECT dynamic imaging.

Methods: A 3D-printed renal phantom mimicking pediatric/adult kidneys was designed. Each kidney subunit, connected to a bladder-bag, was programmably infused with 7.5 MBq of [^99mTc]-Pertechnetate to simulate normal nephrograms. An asymmetry of renal activity was simulated using different activity ratios. Each acquisition was conducted on both conventional NaI(Tl) and 3D-CZT cameras.

Results: The 3D printed phantom enabled the acquisition of consistent and reproducible nephrograms. T_max, T_1/2, and A_{20 - min/max} ratios showed no statistically significant differences between planar and SPECT. Simulated asymmetric renal function demonstrated a strong linear correlation between activity and AUC with r = 0.9455 and 0.9471 (p < 0.0001), respectively for conventional and 3D cameras.

Conclusion: This innovative 3D phantom allowed the acquisition of reproducible nephrograms with parameters comparable to those of clinical examinations. At low activity, 3D-CZT camera acquisitions provided equivalent values to conventional cameras, supporting their use for qualitative imaging and follow-up.

Background: Precise modeling of boron distribution is essential for boron neutron capture therapy (BNCT) dose calculation. While full-three-dimensional (f3D) voxel modeling of ¹⁸F-BPA PET data offers high spatial resolution, its clinical value is limited by intrinsic image resolution-especially PET-and by registration errors in multi-modality image fusion. These factors constrain the reliability of voxel-level dose interpretation and increase computational burden. We propose a hypo-segmentation (hS) method that groups target tissue-to-blood ratio (TBR) values into 0.5-unit intervals to approximate boron distribution. This study retrospectively evaluated four malignant brain tumor cases, comparing dosimetric metrics derived from hS and f3D approaches. Key dose-volume parameters (D_mean, D₈₀, V_{14 Gy-Eq}), spatial agreement (gamma pass rate), and dose-volume curve similarity (dynamic time warping, DTW) were assessed. Dose consistency in normal brain tissue was also evaluated using D_{0.1 cc}, D_mean, and V_{13 Gy-Eq}.

Results: The hS method showed strong agreement with f3D results: within 2% for tumor D_mean, 3% for D₈₀, and 5% for V_{14 Gy-Eq}. Gamma pass rates exceeded 90% in three of four cases. In brain tissue, dose deviations between hS and f3D remained within 2%, demonstrating reliability even in low-uptake, spatially uniform regions. A single small, heterogeneous tumor showed larger discrepancy (D₉₅ deviation = 14.3%, gamma pass rate = 82%), which was mitigated by refining segmentation (h = 0.25).

Conclusions: The hS method offers a clinically practical and computationally efficient alternative to full voxel-wise modeling. It preserves dosimetric fidelity in both tumor and normal brain regions, while aligning with the intrinsic resolution of PET and multimodal imaging. This approach supports accurate yet streamlined BNCT dose planning, particularly in clinical settings where ultra-high spatial granularity provides limited added value.

Trial registration number (trn): ChiCTR2200066473, registered on December 16, 2022.

Background: The aim of this study was to characterize the novel LSD1-specific PET radiotracer [¹⁸F]MNI-1054 in rhesus monkeys and to utilize it to evaluate occupancy of TAK-418, a novel LSD1 inhibitor. To accomplish this, eleven 180-minute dynamic brain PET scans were performed in two rhesus monkeys (1 male/1 female), including baseline scans and a self-block with unlabeled MNI-1054 (3 mg/kg) to assess total levels of specific binding. Displacement and blocking studies with TAK-418 were performed to confirm irreversible binding and to evaluate the dose-occupancy relationship of TAK-418. Scans were also acquired 24- and 48-hours post-TAK-418 dosing to assess LSD1 repopulation rates. Additional baseline and blocking studies with 3.0 mg/kg TAK-418 were acquired in a male monkey to evaluate peripheral binding and occupancy in the testes, an organ with high LSD1 expression. Lastly, whole-body scans were obtained from two animals (1 male/1 female) to evaluate dosimetry.

Results: Across studies, [¹⁸F]MNI-1054 fraction in plasma was ~42% at 30 min and ~14% at 180 min after injection. Tracer kinetics were accurately modeled using an irreversible two-tissue compartment model, yielding K_i as the binding endpoint. The highest specific signal was found in the cerebellum, and the neuroanatomical signal profile was consistent with that of LSD1 expression. The specific signal was blocked in a dose-dependent fashion by the molecularly distinct LSD1 inhibitor TAK-418, with O_max = 95.6% and ED₅₀ = 0.0224 mg/kg in cerebellum. Scans at later time points yielded an LSD1 repopulation half-life estimate of 12.28 h. Evidence of significant LSD1 expression and occupancy was found in testes with 3.0 mg/kg TAK-418, however point occupancy levels could not be reliably estimated from K_i. The estimated whole-body effective dose was ~0.027 mSv/MBq, with the gallbladder wall being the limiting organ (0.18 mSv/MBq).

Conclusions: [¹⁸F]MNI-1054 displayed acceptable brain penetrance, kinetics and LSD1 specificity as well as an acceptable dosimetry. Overall, these findings show its suitability as a viable PET probe to assess the binding profile of LSD1 inhibitors in the brain and support further evaluation in humans.

Background: Left (LAV) and right (RAV) atrial volumes are independent markers of cardiovascular risk in heart failure. Simultaneous assessment of myocardial blood flow (MBF) and atrial volumes might improve the clinical utility of cardiac PET. The aim of this study was to develop and validate an automated method for obtaining atrial volumes from dynamic myocardial perfusion PET scans without ECG-gating.

Results: The atria were segmented automatically using first-pass data from [¹⁵O]-water PET at rest, combining voxel-wise images of bolus area-under-curve and arrival time. Data of multiple patient cohorts were analyzed: retrospective method development in 36 subjects with systolic heart failure with prospective validation in 59 subjects with same-day echocardiograms (primary hypertrophic cardiomyopathy (n = 25), suspected or known cardiac amyloidosis (n = 25) and healthy controls (n = 9)). Test-retest repeatability of PET was assessed in clinical chest pain patients scanned twice on the same day (n = 15). Segmentation was successful in all scans (n=125). PET and echocardiography correlated for LAV in the development cohort (r=0.83, p<0.001) and in the validation cohort (LAV: r=0.83, RAV: r=0.77, both p<0.001). In alignment with echocardiography, PET identified statistically significant differences between healthy controls and subjects with hypertrophied hearts for LAV index: 26 (interquartile range: 24-29) versus 41 (32-51) ml/m², p<0.001, and RAV index: 31 (25-43) versus 48 (38-61) ml/m², p=0.003). Test-retest reproducibility was excellent for LAV (intraclass correlation coefficient ICC=0.96, repeatability coefficient RPC=8.6 ml/m²) and for RAV (ICC=0.96, RPC=11.6 ml/m²).

Conclusion: Left and right atrial volumes can be extracted automatically, accurately and reproducibly using dynamic PET.

Background: This study aimed to investigate the prognostic value of molecular and radiologic characteristics of the primary tumour and axillary lymph nodes (ALNs) on dedicated breast [¹⁸F]FDG PET/MRI in terms of event-free survival (EFS; recurrence and/or death) in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Patients diagnosed with cT2-4N0 or cT1-4N + breast cancer underwent dedicated breast [¹⁸F]FDG PET/MRI pre-, mid-, and post-NAC for response assessment between 2015-2017. Follow-up data per patient on recurrence and death were collected up to July 2025. To evaluate the prognostic value of variables for EFS, time-to-event analyses were used. P-values < 0.10 were considered to indicate statistical significance.

Results: 41 patients with 42 breast tumours underwent dedicated breast [¹⁸F]FDG PET/MRI pre-, mid- and post-NAC for response assessment. Median follow-up time was almost nine years. Univariate Cox regression showed no significant association between pre- and mid-NAC PET- and MRI-derived parameters and EFS. Post-NAC, a higher maximum standardized uptake value (SUVmax; HR 1.41 [90% CI 1.04-1.92], p = 0.029), SUVpeak (HR 1.79 [90% CI 1.04-3.09], p = 0.035), SUVmean (HR 1.80 [90% CI 1.01-3.22], p = 0.046), tumour size (HR 1.04 [90% CI 0.99-1.09], p = 0.087) and signal enhancement ratio (SER; HR 6.46 [90% CI 0.79-52.55], p = 0.081) of the primary tumour were significantly (p < 0.10) associated with recurrence and/or death.

Conclusions: For PET- and MRI-derived parameters, several post-NAC values were predictive of EFS, but no significant association between pre- and mid-NAC values and EFS was found.

Background: Radioimmunotherapy (RIT) with α-emitters represents an attractive alternative for the treatment of refractory Non-Hodgkin lymphoma (NHL) due to the high linear energy transfer and short path length of α-radiation in tissues. We have previously shown that α-RIT with [²¹²Pb]Pb-TCMC-rituximab is potentially useful for treatment of NHL. In this study, we performed radiation dosimetry and evaluated the long-term toxicity in mice to determine safety of [²¹²Pb]Pb-TCMC-rituximab,.

Results: Biodistribution data obtained after intravenous administration of [²¹²Pb]Pb-TCMC-rituximab (185 kBq) in healthy mice were used to calculate the absorbed radiation doses from [²¹²Pb]Pb-TCMC-rituximab. Analyses show that the alveolar-interstitial, kidneys, and spleen receive the highest dose. In order to evaluate the toxicity of RIT for up to 9 months, [²¹²Pb]Pb-TCMC-rituximab was administered intravenously in healthy C57BL/6 mice (277.5 and 555 kBq) and in a B-NHL immunocompetent mouse model (277.5 kBq, specific activity of 37 or 370 MBq/mg). Our previous study revealed a high efficacy of [²¹²Pb]Pb-TCMC-rituximab at 277.5 kBq and that activities of 185-370 kBq of [²¹²Pb]Pb-TCMC-rituximab were well-tolerated. However, in this long-term study, toxicity emerged in healthy mice after four months. The median survival for the 277.5 and 555 kBq groups were 189 and 161 days, respectively. There was no significant hepatic toxicity, but there was a significant increase in urea and creatinine levels at 6 months, indicating long-term renal toxicity (p < 0.001). These results were supported by histopathological data. Long-term renal toxicity is also observed in the toxicity study performed on tumor model with two specific activities of [²¹²Pb]Pb-TCMC-rituximab. Nevertheless, this toxicity was reduced at 370 MBq/mg compared to 37 MBq/mg.

Conclusion: This study shows that long-term toxicity is induced by [²¹²Pb]Pb-TCMC-rituximab, particularly affecting the kidneys. However, it highlights that this renal toxicity can be reduced through optimization, possibly by modifying the specific activity of the treatment.