EJNMMI Research最新文献

Background: Serum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [^99mTc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUV_mean, g/cm³) and volumetric bone mineral density (vBMD, mg/cm³) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUV_mean) was calculated by dividing the SUV_mean by the vBMD and multiplying by 1,000.

Results: SUV_mean correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUV_mean correlated negatively with vBMD (ρ = -0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUV_mean. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUV_mean (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover.

Conclusion: Volumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management.

Background: Peptide receptor radionuclide therapy (PRRT) uses [¹⁷⁷Lu]Lu-[DOTA⁰-Tyr³]octreotate ([¹⁷⁷Lu]Lu-DOTA-TATE) to treat patients with neuroendocrine tumours (NETs) overexpressing the somatostatin receptor 2A (SSTR2A). It has shown significant short-term improvements in survival and symptom alleviation, but there remains room for improvement. Here, we investigated whether combining [¹⁷⁷Lu]Lu-DOTA-TATE with chemotherapeutics enhanced the in vitro therapeutic efficacy of [¹⁷⁷Lu]Lu-DOTA-TATE.

Results: Transfected human osteosarcoma (U2OS + SSTR2A, high SSTR2A expression) and pancreatic NET (BON1 + STTR2A, medium SSTR2A expression) cells were subjected to hydroxyurea, gemcitabine or triapine for 24 h at 37^oC and 5% CO₂. Cells were then recovered for 4 h prior to a 24-hour incubation with 0.7-1.03 MBq [¹⁷⁷Lu]Lu-DOTA-TATE (25 nM) for uptake and metabolic viability studies. Incubation of U2OS + SSTR2A cells with hydroxyurea, gemcitabine, and triapine enhanced uptake of [¹⁷⁷Lu]Lu-DOTA-TATE from 0.2 ± 0.1 in untreated cells to 0.4 ± 0.1, 1.1 ± 0.2, and 0.9 ± 0.2 Bq/cell in U2OS + SSTR2A cells, respectively. Cell viability post treatment with [¹⁷⁷Lu]Lu-DOTA-TATE in cells pre-treated with chemotherapeutics was decreased compared to cells treated with [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy. For example, the viability of U2OS + SSTR2A cells incubated with [¹⁷⁷Lu]Lu-DOTA-TATE decreased from 59.5 ± 22.3% to 18.8 ± 5.2% when pre-treated with hydroxyurea. Control conditions showed no reduced metabolic viability. Cells were also harvested to assess cell cycle progression, SSTR2A expression, and cell size by flow cytometry. Chemotherapeutics increased SSTR2A expression and cell size in U2OS + SSTR2A and BON1 + STTR2A cells. The S-phase sub-population of asynchronous U2OS + SSTR2A cell cultures was increased from 45.5 ± 3.3% to 84.8 ± 2.5%, 85.9 ± 1.9%, and 86.6 ± 2.2% when treated with hydroxyurea, gemcitabine, and triapine, respectively.

Conclusions: Hydroxyurea, gemcitabine and triapine all increased cell size, SSTR2A expression, and [¹⁷⁷Lu]Lu-DOTA-TATE uptake, whilst reducing cell metabolic viability in U2OS + SSTR2A cells when compared to [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy. Further investigations could transform patient care and positively increase outcomes for patients treated with [¹⁷⁷Lu]Lu-DOTA-TATE.

Background: [¹⁸F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [¹⁸F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up.

Results: 110 patients referred for baseline and follow-up standard digital [¹⁸F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTC_{UHD or EARL2} or PERCIST_{UHD or EARL2} mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients.

Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [¹⁸F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.

Background: Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient's prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases.

Case presentation: These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time.

Conclusions: The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Background: Radiolabeled antibody ¹³¹I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic.

Methods: Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of ¹³¹I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+.

Results: Post-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with ¹³¹I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring.

Conclusion: ¹³¹I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402 .

Background: This study aims to evaluate the effect of various background reference regions on spinal ¹⁸F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results.

Results: A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[¹⁸F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2-C7, and T1-T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p < 0.001) compared to the other three regions. However, its coefficient of variation (CV) was significantly lower than that of the C2-C7 (p < 0.0001) and T1-T3 segments (p < 0.05). The SUVRmax values, calculated using the regions of pons, C2-C7 and T1-T3, were found to significantly differentiate between tumors and myelitis (p < 0.05). However, only the pons-based SUVRmean was able to significantly distinguish between the two groups (p < 0.05). Additionally, the pons-based SUVRmax (r = 0.63, p = 0.013) and SUVRmean (r = 0.67, p = 0.007) demonstrated a significant positive correlation with the Ki-67 index.

Conclusions: This study suggests that the pons may be considered a suitable reference region for spinal ¹⁸F-FET PET imaging, which can improve the differentiation between spinal tumors and myelitis. The significant correlation between pons-based SUVR values and the Ki-67 index further highlights the potential of this approach in assessing tumor cell proliferation.

Background: ¹²³I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between ¹²³I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts.

Results: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar ¹²³I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I.

Conclusions: The relationship between cardiac ¹²³I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

Purpose: Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT).

Methods: AIT patients with pathological thyroid uptake on [⁶⁸Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[¹⁸F]FDG PET in terms of SUV_max/SUV_peak/SUV_mean/tissue-to-background ratio (TBR), and with a healthy control group.

Results: Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [⁶⁸Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([⁶⁸Ga]Ga-FAPI (SUV_peak): 7.0 vs. 1.7; p = 0.004/(TBR_bloodpool): 6.8 vs. 1.7; p = 0.002; 2-[¹⁸F]FDG (SUV_peak): 3.9 vs. 1.4; p = 0.004/(TBR_bloodpool): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [⁶⁸Ga]Ga-FAPI and 2-[18F]FDG PET (SUV_peak: 7.3 vs. 5.6; p = 0.104).

Conclusion: Patients with AIT show higher thyroid uptake on [⁶⁸Ga]Ga-FAPI and 2-[¹⁸F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [⁶⁸Ga]Ga-FAPI PET and should prompt a clinical work-up.