EJNMMI Research最新文献

Background: Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancers (PCa) and is targeted in both diagnostic and therapeutic applications. Preclinical studies suggest that short-term androgen blockade may upregulate PSMA expression, potentially enhancing lesion detectability with [⁶⁸Ga]Ga-PSMA-11 positron emission computed tomography (PET) and the therapeutic efficacy of PSMA-targeted radioligands. However, clinical data remains limited and inconsistent. The aim of this study was to assess the impact of short-term non-steroidal androgen blockade therapy (NSAA) on lesion PSMA expression and cellularity using dynamic [⁶⁸Ga]Ga-PSMA-11PET and diffusion-weighted magnetic resonance imaging (MR) for simultaneous estimation of binding potential (BP_ND) and apparent diffusion coefficient (ADC) in hormone-naïve patients with high-risk PCa without bone metastases.

Results: A significant serum prostate specific antigen (PSA) decline was observed in 7/8 patients (median PSA fold change - 88.3% at day 28), indicating positive biochemical response since the NSAA start. Among the observed eight lesions with detectable [⁶⁸Ga]Ga-PSMA-11 uptake, seven exhibited a non-linear and non-monotonic longitudinal trajectory of BP_ND, characterized by a rebound during the mid-treatment phase. In contrast, ADC values progressively increased from baseline for all lesions, suggesting reduced tumour cellularity as treatment progresses. Static SUV measurements poorly reflected these dynamic changes in PSMA expression, indicating limited sensitivity.

Conclusion: Short-term NSAA induces transient PSMA upregulation in hormone-sensitive PCa lesions despite declining cellularity, which may support its cointegration to PSMA-targeted therapies for this population.

Background: The aim of this study was to investigate the preclinical biodistribution and molecular pathway of [⁶⁸Ga]Ga-BP-IDA and to evaluate its clinical suitability for quantitative monitoring of liver function during transarterial radioembolization (TARE) therapy of a hepatocellular carcinoma (HCC).

Results: [⁶⁸Ga]Ga-BP-IDA undergoes hepatobiliary clearance, with uptake into hepatocytes via OATP1B1 and OATP1B3. [⁶⁸Ga]Ga-BP-IDA exhibits demetallation in vivo but is nevertheless suitable for clinical application due to its rapid uptake into functional liver tissue. In a clinical case [⁶⁸Ga]Ga-BP-IDA PET/CT allowed for differentiation of functional liver mass from cancerous tissue and enabled monitoring the effect on liver and tumor volume as well as on residual liver function after TARE therapy. Following TARE treatment, a reduction of the hepatic uptake rate was observed in both non-cancerous liver lobes, but was more pronounced in the right lobe, indicating a correlation to the higher non-targeted radiation dose from the TARE treatment in this lobe. [⁶⁸Ga]Ga-BP-IDA PET/CT thus revealed additional information on liver function impairment which was not represented by CT-based volumetry alone.

Conclusion: [⁶⁸Ga]Ga-BP-IDA PET/CT is a suitable tool for planning and monitoring TARE therapy of primary liver tumors and may complement the limits of volumetry-based methods with functional information about the liver.

Background: The tumor sink effect refers to the sequestration of a radiopharmaceutical compound by tumors, leading to a reduced bioavailability in non-target organs and potential alterations in radiopharmaceuticals distribution. This phenomenon has been widely studied in neuroendocrine, thyroid, and prostate cancers but remains unexplored for melanin-targeting radiopharmaceuticals in metastatic melanoma. [¹³¹I]ICF01012, an arylcarboxamide-derived radiopharmaceutical developed by our team, binds specifically to intra- and extracellular melanin. Given its high ocular uptake, we investigated whether tumor burden influences its biodistribution, particularly in organs at risk such as eyes.

Results: We conducted an ex vivo biodistribution study using syngeneic murine melanoma models (B16-F10, B16-OVA, B16BL6) and correlated tumor volume with radiopharmaceutical uptake. In models, γ-counting revealed significant tumor uptake (18.8 ± 4.5 IA%/g at 24 h after injection of [¹³¹I]ICF01012), which was inversely correlated with ocular uptake (r = -0.7485, p < 0.0001). A significant reduction in ocular uptake was observed in mice with large tumor burdens (-41.8% at 24 h, -47.4% at 72 h, p = 0.022).

Conclusion: These findings suggest that tumor burden impacts [¹³¹I]ICF01012 distribution in non-target organs, with potential clinical implications for dosimetry and toxicity mitigation in radiopharmaceutical therapy for metastatic melanoma. Further studies are needed to refine dosimetric models and assess the translational relevance of this effect in human subjects.

Background: We aimed to estimate ⁸²Rb paediatric dosimetry based on adult biokinetic and prospectively acquired paediatric biokinetic data. Organ absorbed doses (OAD) and effective doses (E) were estimated using ICRP-103 based OLINDA/EXM.2.1 software. We extrapolated paediatric OAD and E from existing adult biokinetic data (OAD_{p, Ab} and E_{p, Ab} respectively). ⁸²Rb EANM paediatric dosage card (PDC) cluster and the recommended administered activity were determined. Ten paediatric participants (M: F 7:3; mean age 8.8 ± 6.6y) underwent prospectively 3D-SiPM ⁸²Rb PET/CT. Using PMOD software, source organs volumes were delineated to obtain source organ time activity curves and participant specific organ masses based on PET/CT data. Subject specific OAD (OAD_p and E_p respectively) were derived from original paediatric data.

Results: ⁸²Rb was assigned to the EANM PDC B-Cluster. Estimated ranges for E_{p, Ab} resp. E_p were 2.19E-02 ̶ 1.15E-03 resp. 9.62E-03 ̶ 1.04E-03 mSv/MBq. E_{p, Ab} resp. E_p with 10 MBq/kg and 5MBq/kg after a single ⁸²Rb infusion was between 0.5 and 0.7 mSv resp. 0.4-0.8 mSv and 0.2-0.4 mSv. The most irradiated organs were the kidneys and the heart wall in infant and newborn group, followed by heart wall in the other age groups, hence, the small intestine, pancreas, lungs, adrenals, and rest of the gastrointestinal tract. ⁸²Rb PET/CT was safe and well-tolerated by all participants.

Conclusions: We firstly provide original dosimetry data for the use of ⁸²Rb PET/CT in the paediatric population, showing reasonably low radiation exposure, and confirming safety and tolerability of ⁸²Rb PET/CT in this population.

Background: Neurooncologists urgently need biomarkers that can optimize the clinical development of PD-L1 targeted immunotherapy in the treatment of glioblastoma. This study evaluated PD-L1 targeted tumor imaging by positron emission tomography (PET) in glioblastoma patients, using the novel macrocyclic peptide radiotracer ¹⁸F-BMS-986229.

Results: Twelve adult postsurgical glioblastoma patients underwent brain PET imaging 1-hour post injection 190±20 MBq of ¹⁸F-BMS-986229. In a subset of patients, dynamic PET scans were obtained for pharmacokinetic modeling in tumors and normal tissues. Tracer kinetics in both tumor sites and normal tissues were well described by a reversible 1-tissue compartment model. Tumor sites demonstrated ¹⁸F-BMS-986229 tracer-avidity (SUV = 1.1 ± 0.4; range, 0.6-1.7) in 10 of 12 cases, with negligible tracer-avidity in normal brain structures. Tumor avidity for ¹⁸F-BMS-986229 on PET was spatially independent of tumor contrast-enhancement on magnetic resonance imaging, indicating that tracer-binding at tumor site was not dependent upon blood-brain barrier breakdown. The observed tumor site low tracer-uptake paralleled low immunohistochemical PD-L1 expression in resected tumors, with no correlations between standardized uptake value versus tumor MGMT methylation, PTEN oncogenic mutation status, tumor mutation burden, or patient overall survival.

Conclusion: This pilot study demonstrates the feasibility of characterizing tumor sites in glioblastoma patients by PD-L1-targeted PET imaging with¹⁸F-BMS-986229, even in patients with low tumor PD-L1 expression. We hypothesize that ¹⁸F-BMS-986229 PET can improve the pharmacometrics of PD-L1-targeted therapy trials.

Trial registration number: NCT02617589. Trial Registration Date: December 1st, 2015.

Background: [^99mTc]Tc-NTP 15 - 5 showed affinity for joint cartilage proteoglycans on preclinical studies but has not been tested in humans. This phase I trial (CARPECT: NCT04481230) aims to define the optimal of [^99mTc]Tc-NTP 15 - 5 injected activity to obtain the best visual contrast of cartilage, without toxicity. Quantitative analyses of cartilage, periarticular uptakes, biodistribution, pharmacokinetic and dosimetry of this new tracer were also studied.

Results: Between November 2020 and June 2022, five patients with unilateral knee osteoarthritis or breast cancer treated with hormonal therapy inducing cartilage disease were injected with [^99mTc]Tc-NTP 15 - 5, at increasing activity levels: 5, 10 and 15 MBq/kg. No major toxicity was reported, according to NCICTC 4.0 scale. With an activity of 15 MBq/Kg, the median rate of joint uptakes higher than diaphysis' one on whole body planar scintigraphy was 80.6% (80.60-85.45) at 2 h p.i. and increased with time. S/N ratio with muscular background measured on SPECT-CT was superior to 3 from 2h30 p.i for cartilage. Uptake evolution depending on time from 1h00 to 6h30 p.i. permitted to discriminate cartilage and pooled proteoglycan structures from background and cartilage from ligaments + tendons for all examination times (p < 0.001), and cartilage from bursa at 1 h p.i. (p < 0.05). Pharmacokinetic, biodistribution and dosimetry were in line with preclinical studies.

Conclusions: This study confirms the usability and accuracy of [^99mTc]Tc-NTP 15 - 5 for cartilage human functional imaging 2 h after injection, at 15 MBq/kg.

Trial registration: Clinicaltrials.gov: NCT04481230. https://clinicaltrials.gov/ct2/show/NCT04481230 . Registration date: November, 12th, 2020.