EJNMMI Research最新文献

Background: Succinate dehydrogenase (SDH) deficient wild-type Gastrointestinal Stromal Tumours (wtGIST) are a rare GIST subtype with limited treatment options. Gallium-68 labelled Gastrin Releasing Peptide Receptor (GRPR) antagonist NeoB has shown promise in PET imaging for multiple primary malignancies. This investigation sought to assess the biodistribution of [⁶⁸Ga]NeoB via PET/CT imaging in metastatic wtGIST patients and aimed to evaluate GRPR expression in lesions to determine the ligand's potential for patient selection in future therapeutic trials.

Results: Twelve patients with histologically confirmed metastatic wtGIST were enrolled. [⁶⁸Ga]NeoB PET/CT imaging was conducted for lesion segmentation and analysis of uptake characteristics. 8 of 12 (66.7%) patients exhibited intense but heterogeneous [⁶⁸Ga]NeoB uptake in lesions, with variable tracer uptake both within and between lesions. Physiological uptake was highest in the pancreas, liver, and spleen. Four patients (33.3%) displayed minimal or no uptake in tumour lesions.

Conclusions: The majority of wtGIST patients in this small cohort show lesions with intense [⁶⁸Ga]NeoB uptake. Heterogeneity of uptake indicates GRPR has highly variable inter- and intralesional expression. NeoB has potential for theranostic application in wtGIST, with limited effective standard of care treatments available. Ongoing trials are investigating the therapeutic use of [¹⁷⁷Lu]NeoB in this setting.

Clinical trial number: Not applicable.

Background: Multiple myeloma (MM) is a heterogeneous malignancy with prognosis significantly affected by high-risk cytogenetic abnormalities (HRCAs). Traditional detection using fluorescence in situ hybridisation is invasive and limited in capturing disease heterogeneity. We aimed to develop and validate radiomics model based on pretreatment [18F] fluoro-deoxyglucose (FDG) positron emission tomography/computed tomographic (18F-FDG PET/CT) imaging to non-invasively predict HRCAs in newly diagnosed MM patients.

Results: Among the 42 candidate models, the Decision Tree classifier utilizing PET active lesions features demonstrated optimal performance in the validation cohort, exhibiting excellent predictive ability (Area Under the Curve (AUC) = 0.89), significantly outperforming the PET metrics model (AUC = 0.84) and clinical model (AUC = 0.74). SHapley Additive exPlanations analysis identified the PET-derived feature as the most important contributor to the model's predictive capacity. The model stratified patients into high-risk and low-risk groups, with the high-risk group exhibiting significantly worse PFS and OS (median PFS: high-risk 24.5 months vs. low-risk 29 months; p = 0.0360; median OS: high-risk 33.5 months vs. low-risk 50 months; p = 0.0023).

Conclusion: As a non-invasive imaging biomarker, PET/CT radiomics holds potential for predicting high-risk cytogenetic status and facilitating patient prognosis stratification Further large-scale, multi-center prospective validations are essential to confirm its utility for personalized therapeutic decision-making in MM.

Background: Terbium-161 (¹⁶¹Tb) is a promising β⁻-emitter for theragnostics. However, its complex photon emission pattern-including intense X-rays and low-yield, high-energy γ-emissions-may complicate image-based quantification. This study aimed to assess the feasibility of accurate SPECT/CT-based ¹⁶¹Tb dosimetry through a series of phantom measurements using a GE Discovery NM/CT 670 Pro system. Three collimators were evaluated: extended low-energy general-purpose (ELEGP), low-energy high-resolution (LEHR), and medium-energy general-purpose (MEGP), using two separate energy windows: around the 75 keV γ-peak (± 10%), and around the 49 keV γ-peak and nearby X-rays (40.7-62.9 keV). A clinical OSEM reconstruction algorithm was employed.

Results: On average, the SPECT calibration factors (CFs) were 2-fold higher with ELEGP compared to MEGP and LEHR, and 3-fold higher at 49 keV compared to 75 keV. For each collimator, derived CFs varied substantially depending on measurement and volume-of-interest geometry-more so at 49 keV, compared to 75 keV. Measurements of two 3D-printed kidney inserts revealed superior visual image quality with LEHR compared to ELEGP and MEGP. Across all collimators, the 75 keV window provided better spatial resolution and contrast than the 49 keV window. An anthropomorphic phantom study, including a LungSpine phantom with 8 spherical inserts and 3 different background activity levels, demonstrated a greater quantitative accuracy for MEGP compared to LEHR and ELEGP, with statistical significance for both energy windows (p ≤ 0.001). Errors were generally larger at 49 keV compared to 75 keV. For the low-energy collimators, considerable septal penetration (e.g., at 292 and 475 keV) was observed, along with systematic underestimation at high activity levels.

Conclusions: This study demonstrates that highly accurate SPECT/CT-based ¹⁶¹Tb quantification is feasible, further cementing ¹⁶¹Tb as a viable theragnostic alternative. A MEGP collimator, a 75 keV window, and a CF derived from a homogeneous cylinder measurement appears preferable. The 49 keV window could be useful at late imaging time points, given its high sensitivity, if further optimized. Degradation from penetration and subsequent downscatter may be mitigated with a more refined reconstruction. Further investigations into dead-time effects are encouraged.

Background: Total Body PET/CT is increasingly used in clinical practice, but its benefits for lung cancer staging are not fully established. This study aimed to evaluate the impact of Total Body PET/CT on lung cancer staging compared to traditional Whole-Body PET/CT.

Results: Among the 763 patients, 289 (37.9%) had stage IV disease, with 96 (33.2%) showing limb metastases, including those in the lower limbs (legs) or also the upper limbs (arms). Compared to Whole-Body PET/CT, Total Body PET/CT detected additional metastases in 60.4% (58/96) of patients with limb metastases, representing 20.1% (58/289) of all stage IV patients. These included 96 bone and 43 muscle metastases. In patients with isolated limb metastases (n = 31), Total Body PET/CT detected additional metastases in 13 (41.9%) compared to Whole-Body PET/CT, altering tumor staging in only one patient (0.3% of stage IV patients). In those with multiple limb metastases (n = 65), Total Body PET/CT detected additional metastases in 45 (69.2%), but staging remained unchanged. Distal limb metastasis was strongly associated with concurrent bone (OR = 8.288, 95%CI: 3.642-18.861) and muscle metastases outside the limb (OR = 3.911, 95%CI: 1.624-9.417) (both P < 0.001). Additionally, Total Body PET/CT detected acute arthritis in 193 (25.3%) patients and benign lesions (e.g., varicose veins, neurogenic tumors, lipomas, fractures) in 68 (8.9%) compared to Whole-Body PET/CT.

Conclusion: Whole-Body imaging is sufficient to meet the clinical staging requirements for lung cancer. Although Total Body PET/CT detects more distal metastases in approximately 20% of stage IV lung cancer patients, it led to stage shift in only one patient and 0% change in the oncologic treatment.

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.