Journal of Nuclear Medicine最新文献

Our objective was to assess the diagnostic value of the sentinel node (SN) procedure for lymph node staging in primary intermediate- and high-risk prostate cancer patients with node-negative results on prostate-specific membrane antigen PET/CT (miN0). Methods: From 2016 to 2022, 154 patients with primary, miN0 PCa were retrospectively included. All patients had a Briganti nomogram-assessed nodal risk of more than 5% and underwent a robot-assisted SN procedure for nodal staging. The prevalence of nodal metastases at histopathology and the occurrence of surgical complications according to the Clavien-Dindo classification were evaluated. Results: The SN procedure yielded 84 (14%) tumor-positive lymph nodes with a median metastasis size of 3 mm (interquartile range, 1-4 mm). In total, 55 patients (36%) were reclassified as pN1. A complication of Clavien-Dindo grade 3 or higher occured in 1 patient (0.6%). Conclusion: The SN procedure classified 36% of patients with miN0 prostate cancer with an elevated risk of nodal metastases as pN1.

²²³Ra, a targeted α-therapy, is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. In the phase 3 ALSYMPCA study, ²²³Ra prolonged survival and improved quality of life versus placebo. Our real-world study, PARABO, investigated pain and bone pain-related quality of life in patients with mCRPC and symptomatic bone metastases receiving ²²³Ra in clinical practice. Methods: PARABO was a prospective, observational, noninterventional single-arm study conducted in nuclear medicine centers across Germany (NCT02398526). The primary endpoint was a clinically meaningful pain response (≥2-point improvement from baseline for the worst-pain item score in the Brief Pain Inventory-Short Form). Results: The analysis included 354 patients, who received a median of 6 ²²³Ra injections (range, 1-6). Sixty-seven percent (236/354) received 5-6 injections, and 33% (118/354) received 1-4 injections. Of 216 patients with a baseline worst-pain score of more than 1, 59% (128) had a clinically meaningful pain response during treatment. Corresponding rates were 67% (range, 98/146) with 5-6 ²²³Ra injections versus 43% (range, 30/70) with 1-4 injections, 60% (range, 60/100) in patients with no more than 20 lesions versus 59% (range, 65/111) in those with more than 20 lesions, and 65% (range, 69/106) in patients without prior or concomitant opioid use versus 54% (range, 59/110) in those with prior or concomitant opioid use. Mean subscale scores (pain severity and pain interference) on the Brief Pain Inventory-Short Form improved during treatment. Conclusion: ²²³Ra reduced pain in patients with mCRPC and symptomatic bone metastases, particularly in patients who received 5-6 injections. The extent of metastatic disease did not impact pain response.

Bone marrow suppression is a common side effect after [¹⁷⁷Lu]Lu-DOTATATE treatment of neuroendocrine neoplasms. Neuroendocrine neoplasms share expression of somatostatin receptor type 2 with CD34-positive hematopoietic progenitor cells, potentially leading to active uptake in the radiosensitive red marrow region where these cells are located. This study aimed to identify and quantify specific red marrow uptake using SPECT/CT images collected after the first treatment cycle. Methods: Seventeen patients diagnosed with neuroendocrine neoplasms were treated with [¹⁷⁷Lu]Lu-DOTATATE. Seven of them had confirmed bone metastases. After the first treatment cycle, each patient went through 4 SPECT/CT imaging sessions 4, 24, 48, and 168 h after administration. Monte Carlo-based reconstructions were used to quantify activity concentrations in tumors and multiple skeletal sites presumed to house red marrow: the T9-L5 vertebrae and the ilium portion of the hip bones. The activity concentration from the descending aorta was used as input in a compartment model intended to establish a pure red marrow biodistribution by separating the nonspecific blood-based contribution from the specific activity concentration in red marrow. The biodistributions from the compartment model were used to perform red marrow dosimetry at each skeletal site. Results: Increased uptake of [¹⁷⁷Lu]Lu-DOTATATE was observed in the T9-L5 vertebrae and hip bones in all 17 patients compared with activity concentrations in the aorta. The mean specific red marrow uptake was 49% (range, 0%-93%) higher than the nonspecific uptake. The median (±SD) total absorbed dose to the red marrow was 0.056 ± 0.023 Gy/GBq and 0.043 ± 0.022 Gy/GBq for the mean of all vertebrae and hip bones, respectively. The patients with bone metastases had an absorbed dose of 0.085 ± 0.046 Gy/GBq and 0.069 ± 0.033 Gy/GBq for the vertebrae and hip bones, respectively. The red marrow elimination phase was statistically slower in patients with fast tumor elimination, which is in line with transferrin transport of ¹⁷⁷Lu back to the red marrow. Conclusion: Our results suggest that specific red marrow uptake of [¹⁷⁷Lu]Lu-DOTATATE is in line with observations of somatostatin receptor type 2-expressing hematopoietic progenitor cells within the bone marrow. Blood-based dosimetry methods fail to account for the prolonged elimination of specific uptake and underestimate the absorbed dose to red marrow.

Coronary ¹⁸F-sodium fluoride (¹⁸F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary ¹⁸F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary ¹⁸F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary ¹⁸F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary ¹⁸F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary ¹⁸F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary ¹⁸F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary ¹⁸F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary ¹⁸F-fluoride uptake is a temporally stable marker of established and progressive disease.

¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer. Rarer treatment-related adverse events have not yet been described. Methods: We present case reviews of 2 men with a marked hypocalcemic osteosclerotic response to ¹⁷⁷Lu-PSMA-I&T therapy. A clinical dataset of ¹⁷⁷Lu-PSMA-I&T therapy was evaluated to estimate the incidence and clinical association with hypocalcemia. Results: Forty-one of the 127 men (32%) had a serum calcium drop, and 6 (5%) developed clinical hypocalcemia during ¹⁷⁷Lu-PSMA therapy. The baseline total tumor volume was significantly higher in those who developed hypocalcemia (median, 3,249 cm³ [interquartile range, 1,856-3,852] vs. 465 [interquartile range 135-1,172]; P = 0.002). The mean prostate-specific antigen response in those with hypocalcemia was 78% (SD, 24%). Conclusion: Hypocalcemia may occur in response to ¹⁷⁷Lu-PSMA-I&T, particularly with both high-volume bone metastases and a significant prostate-specific antigen response, and may be severe, requiring corticosteroids. Further evaluation of ¹⁷⁷Lu-PSMA-induced hypocalcemia is required to better understand mechanisms, optimal treatments, and repercussions from any subsequent osteosclerotic response.

Erdheim-Chester disease (ECD) involves multiple organs and tissues and has diverse manifestations, which makes it difficult to distinguish lesions caused by ECD from those caused by other diseases. Variable degrees of fibrosis are present in ECD. Therefore, we conducted a prospective cohort study to explore the ability of ⁶⁸Ga fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) PET/CT to detect lesions in ECD patients. Methods: Fourteen patients diagnosed with ECD, as confirmed by histology, were included in this study. For every patient, ⁶⁸Ga-FAPI PET/CT and ¹⁸F-FDG PET/CT were conducted within 1 wk. The positive rate and SUV_max of the lesions in the involved organs were compared between the examinations. Results: The most commonly involved organs were bone (100%), heart (57.1%), lung (57.1%), kidney (42.9%), and peritoneum or omentum (35.7%); other common manifestations were intracranial infiltration (50%) and cutaneous infiltration (35.7%). ⁶⁸Ga-FAPI PET/CT detected 64 of 67 lesions in 14 patients, whereas ¹⁸F-FDG PET/CT detected 51 of 67 lesions (P = 0.004). The SUV_max for ⁶⁸Ga-FAPI PET/CT was significantly higher than the SUV_max for ¹⁸F-FDG PET/CT of the heart (4.9 ± 2.4 vs. 2.8 ± 1.2, respectively; P = 0.050), lung or pleura (6.8 ± 4.9 vs. 3.1 ± 1.3, respectively; P = 0.025), peritoneum or omentum (5.7 ± 3.6 vs. 2.8 ± 1.7, respectively; P = 0.032), and kidney or perinephric infiltration (4.9 ± 1.2 vs. 2.9 ± 1.1, respectively; P = 0.009). Conclusion: The detectivity of ⁶⁸Ga-FAPI PET/CT is superior to that of ¹⁸F-FDG PET/CT. Moreover, ⁶⁸Ga-FAPI PET/CT has a better image contrast and higher SUV_max for lesions in multiple organs including the heart, lungs, peritoneum, and kidneys. ⁶⁸Ga-FAPI PET/CT is a promising tool to assess pathologic features and disease extent in ECD patients.

Recent innovative strategies have dramatically redefined the therapeutic landscape for treating multiple myeloma patients. In particular, the development and application of immunotherapy and high-dose therapy have demonstrated high response rates and have prolonged remission duration. Over the past decade, new morphologic or hybrid imaging techniques have gradually replaced conventional skeletal surveys. PET/CT using ¹⁸F-FDG is a powerful imaging tool for the workup at diagnosis and for therapeutic evaluation allowing medullary and extramedullary assessment. The independent negative prognostic value for progression-free and overall survival derived from baseline PET-derived parameters such as the presence of extramedullary disease or paramedullary disease, as well as the number of focal bone lesions and SUV_max, has been reported in several large prospective studies. During therapeutic evaluation, ¹⁸F-FDG PET/CT is considered the reference imaging technique because it can be performed much earlier than MRI, which lacks specificity. Persistence of significant abnormal ¹⁸F-FDG uptake after therapy is an independent negative prognostic factor, and ¹⁸F-FDG PET/CT and medullary flow cytometry are complementary tools for detecting minimal residual disease before maintenance therapy. The definition of a PET metabolic complete response has recently been standardized and the interpretation criteria harmonized. The development of advanced PET analysis and radiomics using machine learning, as well as hybrid imaging with PET/MRI, offers new perspectives for multiple myeloma imaging. Most recently, innovative radiopharmaceuticals such as C-X-C chemokine receptor type 4-targeted small molecules and anti-CD38 radiolabeled antibodies have shown promising results for tumor phenotype imaging and as potential theranostics.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) have shown promise as cancer diagnostic agents; however, the relatively short tumor retention of FAPIs may limit their application in radioligand therapy. In this paper, we report the design, synthesis, and evaluation of a FAPI tetramer. The aim of the study was to evaluate the tumor-targeting characteristics of radiolabeled FAPI multimers in vitro and in vivo, thereby providing information for the design of FAP-targeted radiopharmaceuticals based on the polyvalency principle. Methods: FAPI tetramers were synthesized on the basis of FAPI-46 and radiolabeled with ⁶⁸Ga, ⁶⁴Cu, and ¹⁷⁷Lu. In vitro FAP-binding characteristics were identified using a competitive cell-binding experiment. To evaluate their pharmacokinetics, small-animal PET, SPECT, and ex vivo biodistribution analyses were performed on HT-1080-FAP and U87MG tumor-bearing mice. In addition, the 2 tumor xenografts received radioligand therapy with ¹⁷⁷Lu-DOTA-4P(FAPI)₄, and the antitumor efficacy of the ¹⁷⁷Lu-FAPI tetramer was evaluated and compared with that of the ¹⁷⁷Lu-FAPI dimer and monomer. Results: ⁶⁸Ga-DOTA-4P(FAPI)₄ and ¹⁷⁷Lu-DOTA-4P(FAPI)₄ were highly stable in phosphate-buffered saline and fetal bovine serum. The FAPI tetramer exhibited high FAP-binding affinity and specificity both in vitro and in vivo. ⁶⁸Ga-, ⁶⁴Cu-, and ¹⁷⁷Lu-labeled FAPI tetramers exhibited higher tumor uptake, longer tumor retention, and slower clearance than FAPI dimers and FAPI-46 in HT-1080-FAP tumors. The uptake (percentage injected dose per gram) of ¹⁷⁷Lu-DOTA-4P(FAPI)₄, ¹⁷⁷Lu-DOTA-2P(FAPI)₂, and ¹⁷⁷Lu-FAPI-46 in HT-1080-FAP tumors at 24 h was 21.4 ± 1.7, 17.1 ± 3.9, and 3.4 ± 0.7, respectively. Moreover, ⁶⁸Ga-DOTA-4P(FAPI)₄ uptake in U87MG tumors was approximately 2-fold the uptake of ⁶⁸Ga-DOTA-2P(FAPI)₂ (SUV_mean, 0.72 ± 0.02 vs. 0.42 ± 0.03, P < 0.001) and more than 4-fold the uptake of ⁶⁸Ga-FAPI-46 (0.16 ± 0.01, P < 0.001). In the radioligand therapy study, remarkable tumor suppression was observed with the ¹⁷⁷Lu-FAPI tetramer in both HT-1080-FAP and U87MG tumor-bearing mice. Conclusion: The satisfactory FAP-binding affinity and specificity, as well as the favorable in vivo pharmacokinetics of the FAPI tetramer, make it a promising radiopharmaceutical for theranostic applications. Improved tumor uptake and prolonged retention of the ¹⁷⁷Lu-FAPI tetramer resulted in excellent characteristics for FAPI imaging and radioligand therapy.

Tau PET tracers are expected to be sufficiently sensitive to track the progression of age-related tau pathology in the medial temporal cortex. The tau PET tracer N-(4-[¹⁸F]fluoro-5-methylpyridin-2-yl)-7-aminoimidazo[1,2-a]pyridine ([¹⁸F]SNFT-1) has been successfully developed by optimizing imidazo[1,2-a]pyridine derivatives. We characterized the binding properties of [¹⁸F]SNFT-1 using a head-to-head comparison with other reported ¹⁸F-labeled tau tracers. Methods: The binding affinity of SNFT-1 to tau, amyloid, and monoamine oxidase A and B was compared with that of the second-generation tau tracers MK-6240, PM-PBB3, PI-2620, RO6958948, JNJ-64326067, and flortaucipir. In vitro binding properties of ¹⁸F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative disease spectra. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of [¹⁸F]SNFT-1. Results: In vitro binding assays demonstrated that [¹⁸F]SNFT-1 possesses high selectivity and high affinity for tau aggregates in Alzheimer disease (AD) brains. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with AD showed a higher signal-to-background ratio for [¹⁸F]SNFT-1 than for the other tau PET tracers and no significant binding with non-AD tau, α-synuclein, transactiviation response DNA-binding protein-43, and transmembrane protein 106B aggregates in human brain sections. Furthermore, [¹⁸F]SNFT-1 did not bind significantly to various receptors, ion channels, or transporters. [¹⁸F]SNFT-1 showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites. Conclusion: These preclinical data suggest that [¹⁸F]SNFT-1 is a promising and selective tau radiotracer candidate that allows the quantitative monitoring of age-related accumulation of tau aggregates in the human brain.