EJNMMI Research最新文献

Background: Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with ¹¹¹In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of ¹¹¹In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo RESULTS: Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.

Conclusion: Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.

Trial registration: ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .

Clinicaltrials: gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .

Background: The optimal regimen for ¹⁷⁷Lu-labeled prostate-specific membrane antigen-targeted radioligand therapy, including treatment intervals, remains under study, with evidence suggesting shorter intervals could benefit patients with high disease volume and rapid progression. This retrospective analysis evaluated treatment toxicity, PSA response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) in matched cohorts of mCRPC patients receiving 177Lu-PSMA-RLT at 4-week versus 6-week intervals.

Results: A PSA response (PSA decline ≥ 50%) was achieved in 47.8% and 21.7% of patients in the 4-week and 6-week treatment interval groups, respectively (p = 0.12). There was a trend towards longer PSA-PFS in the 4-week group compared to the 6-week group (median PSA-PFS, 26.0 weeks vs. 18.0 weeks; HR 0.6; p = 0.2). Although not statistically significant, there was a trend towards shorter OS in the 4-week group compared to the 6-week group (median OS, 15.1 months vs. 18.4 months; HR 1.3; p = 0.5). The 4-week group had a significantly greater decrease in leucocyte and platelet counts compared to the 6-week group (38.5% vs. 18.2% and 26.7% vs. 10.7%; p = 0.047 and p = 0.02). Severe adverse events were modest in both groups.

Conclusions: Intensifying treatment intervals from 6 weeks to 4 weeks showed some improvements in PSA response and PSA-PFS for mCRPC patients, but did not significantly affect OS. Additionally, bone marrow reserve was significantly reduced with the intensified regimen. Therefore, the overall benefit remains uncertain, and further prospective studies are needed to compare 4-week and 6-week intervals regarding toxicity, treatment response, and outcome.

Background: It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of ¹⁸F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (¹⁸F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing ¹⁸F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion's voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean).

Results: Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%.

Conclusion: The ¹⁸F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.

Background: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [¹⁸F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [¹⁸F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [¹⁸F]FDG-PET/CT.

Results: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15-20 min before [¹⁸F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [¹⁸F]FDG uptake pattern was evaluated visually and [¹⁸F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1-5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875).

Conclusions: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.

Background: Fluorine 18-labelled tetrafluoroborate ([¹⁸F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [¹⁸F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [¹⁸F]TFB and compare its properties to [¹²⁴I]IodinePET/CT in patients with metastatic thyroid cancer.

Methods: Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [¹⁸F]TFB and were given 230 ± 9 MBq [¹²⁴I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [¹²⁴I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [¹⁸F]TFB and [¹²⁴I]Iodine were calculated.

Results: Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [¹⁸F]TFB and 30 (91%) on [¹²⁴I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [¹²⁴I]Iodine PET/CT with a median SUV_max of 3.3 (range, 0.4-285.0). All of these lesions were [¹⁸F]TFB-negative.

Conclusion: [¹⁸F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer.

Trial registration number: NCT03196518, registered on June 22, 2017.

Background: The alpha-emitting radionuclide therapy [²²³Ra]RaCl₂ (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.

Methods: Prospective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.

Results: A total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7-16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1-4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1-2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3-5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1-13.9), P < 0.001).

Conclusion: BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.

Trial registration: Clinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1 .

Background: Skeletal muscles are vital for daily function, yet assessing their injuries remain challenging. We aimed to elucidate the effectiveness of ⁶⁸Ga-FAPI-04 in evaluating skeletal muscle remodeling.

Results: C2C12 cells were subjected to graded H₂O₂ stimulation in vitro, revealing an initial rise and subsequent decline in fibroblast activation protein (FAP) expression as H₂O₂ concentration increased. In vivo, a murine triceps surae injury model was created using various solutions to simulate normal repair, mild repair failure, and severe repair failure. Assessments were conducted on days 1, 3, 7, and 14 using PET, MRI, and ultrasound. With ⁶⁸Ga-FAPI-04, the normal and mild repair failure groups showed significantly higher SUVmax and T/B ratios on day 1 compared to the severe repair failure group. These values gradually decreased in the normal repair group, becoming negligible after day 7. MRI results for the normal repair group showed low to moderate signal intensity by day 7. A clinical study retrospectively evaluated post-hip arthroplasty patient images at intervals of 1 month, 2-3 months, 5-6 months, and over 7 months. In these patients, ¹⁸F-FDG SUVmax and volume remained relatively stable over time, while ⁶⁸Ga-FAPI-04 SUVmax initially increased, then decreased, with a consistent reduction in volume.

Conclusion: In skeletal muscle injuries, FAP demonstrates a distinctive mechanism of action, and ⁶⁸Ga-FAPI-04, in comparison to other tests, more precisely captures alterations in lesion site uptake intensity and volume.

Trial registration: Trial registration: ChiCTR2000041204. Registered 22 December 2020, https://www.chictr.org.cn/showproj.html?proj=66211.

Background: Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [¹⁵O]H₂O PET brain scan during vasodilation to a [^99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).

Case presentation: A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [¹⁵O]H₂O PET and [^99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion.

Conclusions: The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.

Background: Fibroblast activation protein (FAP) has gained attention as a promising molecular target with potential utility for cancer diagnosis and therapy. [⁶⁸Ga]Ga-labeled FAP-targeting peptides have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To meet the applicable demand for peptide-based FAP tracers with high patient throughput, we herein report the radiosynthesis, preclinical evaluation, and the first-in-human imaging of a novel [¹⁸F]F-labeled FAP-targeting peptide.

Results: [¹⁸F]AlF-FAP-NUR was automatedly prepared within 45 min with a non-decay corrected radiochemical yield of 18.73 ± 4.25% (n = 3). Compared to [⁶⁸Ga]Ga-FAP-2286, the [¹⁸F]F-labeled peptide demonstrated more rapid, higher levels of cellular uptake and internalization, and lower levels of cellular efflux in HT1080-FAP cells. Micro-PET imaging and biodistribution studies conducted on xenograft mice models revealed a similar distribution pattern between the two tracers. However, [¹⁸F]AlF-FAP-NUR demonstrated significantly higher tumor-specific uptake resulting in improved Tumor-Background Ratios (TBRs). In the patients, a significant accumulation of [¹⁸F]AlF-FAP-NUR was found in the primary tumor. High uptake of the tracer within the bladder indicated that its major route of excretion was through urine.

Conclusions: Based on the physical imaging properties and longer half-life of [¹⁸F]F, [¹⁸F]AlF-FAP-NUR exhibited promising characteristics such as enhanced tumor-specific accumulation and elevated TBRs, which made it a viable candidate for further clinical investigation.

Trial registration: www.Chictr.org.cn , ChiCTR2300076976 Retrospectively registered 25 October 2023. at, URL: https://www.chictr.org.cn/showproj.html?proj=206753 .

Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient - in vitro PDOs - in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns.

Results: The main liver metastasis of the CRC patient exhibited high 2-[¹⁸F]FDG uptake and moderate and focal [⁶⁸Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[¹⁸F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [⁶⁸Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [⁶⁸Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking.

Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [⁶⁸Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[¹⁸F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients.