18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

Detection of HER2 expression using 99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial.

BACKGROUND: 99mTc radiolabeled nanobody NM-02 (99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99mTc-NM-02 uptake and HER2 expression in patients with breast cancer. METHODS: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99mTc-NM-02 SPECT/computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUVmax) of 18F-FDG and SUVmax and mean SUV (SUVmean) of 99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. RESULTS: No meaningful relationship was observed between 18F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18F-FDG PET/CT. 99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. CONCLUSIONS: 99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. TRIAL REGISTRATION: NCT04674722, Date of registration: December 19, 2020.

Comparison of Cardiac Activated Fibroblast Imaging and Magnetic Resonance Imaging in Patients with COVID-19-Related Myocarditis.

Background: This study aimed to explore the association between cardiac fibroblast activation and cardiac magnetic resonance (CMR) imaging parameters in patients with myocarditis following infection with coronavirus 2019 (COVID-19). Methods: In this prospective study, four patients with COVID-19-related myocarditis underwent 99mTc-labeled-hydrazinonicotinamide-fibroblast activation protein inhibitor-04 (99mTc-HFAPi) single photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging. Segmental 99mTc-HFAPi activity was quantified as the percentage of average segmental myocardial count × global left ventricular target-to-background ratio. T1/T2 values, extracellular volume (ECV), and late gadolinium enhancement (LGE) were analyzed by CMR. The consistency between myocardial 99mTc-HFAPi activity and CMR parameters was explored. Results: In patients with myocarditis, the proportion of segments with abnormal 99mTc-HFAPi activity was significantly higher than in those with abnormal LGE (81.25% vs. 60.93%, p = 0.011), abnormal T2 (81.25% vs. 50.00%, p < 0.001), and abnormal ECV (81.25% vs. 59.38%, p = 0.007); however, they were similar in those with abnormal native T1 (81.25% vs. 73.43%, p = 0.291). Meanwhile, 99mTc-HFAPi imaging exhibited good consistency with native T1 (kappa = 0.69). Conclusions: Increased cardiac 99mTc-HFAPi activity is present in COVID-19-related myocarditis, which is correlated with the native T1 values in CMR.

Early response monitoring during [177Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study.

PURPOSE: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy. METHODS: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021-01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan-Meier methodology (log-rank test). RESULTS: Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4-26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09-0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07-0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16-0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01-0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02-0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively). CONCLUSION: Six weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice.

68Ga-Trivehexin PET/CT: a promising novel tracer for primary hyperparathyroidism.

INTRODUCTION: This study aims to assess 68Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [99mTc]Tc-MIBI scintigraphy-SPECT/CT (MIBI scan) in patients with primary hyperparathyroidism (PHPT). METHODS: The cohort comprised 13 patients diagnosed with PHPT based on biochemical analyses, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels. Each participant underwent cervical ultrasonography, MIBI scan, and 68Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [18F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. 68Ga-Trivehexin PET/CT findings were compared with other modalities and PTH-WO results. RESULTS: Ten patients had sporadic PHPT, while 3 were diagnosed with MEN-1 syndrome-associated PHPT. One patient did not have any identifiable parathyroid lesion across the imaging modalities. On a patient-based analysis, MIBI scan and 68Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, 68Ga-Trivehexin PET/CT detected 7 additional parathyroid lesions that were negative on the MIBI scan. Consequently, 17 lesions were identified and confirmed as hyperfunctioning parathyroid tissue through imaging, PTH-WO, or a combination of both modalities. In lesion-based evaluation, 68Ga-Trivehexin identified 16 lesions compared to 10 by MIBI scan, resulting in a detection rate of 94.1% and 58.8%, respectively. Notably, in three patients who underwent [18F]fluorocholine PET/CT, no lesions were detected; yet 68Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients. CONCLUSION: Our study provides the first evidence that 68Ga-Trivehexin PET/CT can effectively identify hyperfunctioning parathyroid tissue with a high detection rate warranting further investigations to comprehensively explore its potential in PHPT management.

Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

EANM position paper on challenges and opportunities of full-ring 360° CZT bone imaging: it's time to let go of planar whole-body bone imaging.

The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON® and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study.

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.

Diagnostic efficacy of [99mTc]Tc-PSMA SPECT/CT for prostate cancer: a meta-analysis.

BACKGROUND: Prompt and accurate diagnosis of prostate cancer (PCa) is of paramount importance for effective treatment planning. While Gallium-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has proven efficacy in detecting PCa, limited availability poses challenges. As a potential alternative, [99mTc]Tc-PSMA single photon emission computed tomography (SPECT)/computed tomography (CT) holds promise. This systematic review and meta-analysis aimed to evaluate the diagnostic value of [99mTc]Tc-PSMA SPECT/CT for prostate cancer. METHODS: A comprehensive search of PubMed, Cochrane, EMBASE, Scopus, Ovid, and Web of Science databases was conducted until July 2024. Sensitivity and specificity data were extracted to assess the diagnostic accuracy of [99mTc]Tc-PSMA SPECT/CT, while the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate study quality. Statistical analyses were performed using STATA 18, with MetaDisc 1.4 employed to detect threshold effects. Diagnostic accuracy indicators, including sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (LR-), and positive likelihood ratio (LR+), were pooled. The area under the curve (AUC) of the combined model was calculated using summary receiver-operating characteristic (SROC) curves. RESULTS: Seven studies meeting the inclusion criteria were identified from an initial pool of 1467 articles, with no publication bias observed. The pooled sensitivity, specificity, and AUC of [99mTc]Tc-PSMA SPECT/CT were found to be 0.89 (95% CI, 0.84-0.93), 0.92 (95% CI, 0.67-0.99), and 0.93 (95% CI, 0.90-0.95), respectively. Additionally, the comprehensive diagnostic odds ratio, diagnostic score, positive likelihood ratio, and negative likelihood ratio were calculated as 95.24 (95% CI, 17.30-524.41), 4.56 (95% CI, 2.85-6.26), 11.35 (95% CI, 2.31-55.71), and 0.12 (95% CI, 0.08-0.18), respectively. CONCLUSIONS: In conclusion, our findings demonstrate that [99mTc]Tc-PSMA SPECT/CT exhibits favorable diagnostic performance for prostate cancer and can provide valuable supplementary information, particularly in regions and settings where [68Ga]Ga-PSMA PET/CT availability is limited, such as remote areas. These results highlight the potential of [99mTc]Tc-PSMA SPECT/CT as a valuable tool in the diagnosis and management of prostate cancer, warranting further investigation and validation in larger patient cohorts.

Noninvasive quantitative evaluation of viable islet grafts using 111 In-exendin-4 SPECT/CT.

Islet transplantation (IT) is an effective ß-cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their ß-cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive ß-cell imaging is required. In this study, we investigated the utility of the 111 Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} (111 In exendin-4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin-induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6-week observation following IT, the ex-vivo liver graft uptake of 111 In-exendin-4 was compared with the liver insulin content. In addition, the in-vivo liver graft uptake of 111 In exendin-4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex-vivo liver graft uptake in the 400-islet-transplanted group was significantly higher than that in the control and the 150-islet-transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in-vivo SPECT/CT displayed liver islet grafts, and uptakes were corroborated by histological liver BCM. 111 In-exendin-4 SPECT/CT can be used to visualize and evaluate liver islet grafts noninvasively after intraportal IT.

Synthesis and Preliminary Study of 99mTc-Labeled HYNIC-FAPi for Imaging of Fibroblast Activation Proteins in Tumors.

Fibroblast activation protein (FAP) is an emerging target for cancer diagnosis. Different types of FAP inhibitor (FAPI)-based radiotracers have been developed and applied for tumor imaging. However, few FAPI tracers for single photon emission computed tomography (SPECT) imaging have been reported. SPECT imaging is less expensive and more widely distributed than positron emission tomography (PET), and thus, 99mTc-labeled FAPIs would be more available to patients in developing regions. Herein, we developed a FAPI-04-derived radiotracer, HYNIC-FAPi-04 (HFAPi), for SPECT imaging. 99mTc-HFAPi, with a radiochemical purity of >98%, was prepared using a kit formula within 30 min. The specificity of 99mTc-HFAPi for FAP was validated by a cell binding assay in vitro and SPECT/CT imaging in vivo. The binding affinity (Kd value) of 99mTc-HFAPi for human FAP and murine FAP was 4.49 and 2.07 nmol/L, respectively. SPECT/CT imaging in HT1080-hFAP tumor-bearing mice showed the specific FAP targeting ability of 99mTc-HFAPi in vivo. In U87MG tumor-bearing mice, 99mTc-HFAPi had a higher tumor uptake compared with that of HT1080-hFAP and 4T1-mFAP tumor models. Interestingly, 99mTc-HFAPi showed a relatively high uptake in some murine joints. 99mTc-HFAPi accumulated in tumor lesions with a high tumor-to-background ratio. A preliminary clinical study was also performed in breast cancer patients. Additionally, 99mTc-HFAPi exhibited an advantage over 18F-FDG in the detection of lymph node metastatic lesions in breast cancer patients, which is helpful in improving treatment strategies. In short, 99mTc-HFAPi showed excellent affinity and specificity for FAP and is a promising SPECT radiotracer for (re)staging and treatment planning of breast cancers.

Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002.

Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models. However, little is known about its absorption, distribution, and excretion in live organisms. Here, we performed a comprehensive biodistribution assessment with a gallium-67 radiolabeled derivative of IDR-1002 using nuclear tracing techniques. Various dose levels of the radiotracer (2-40 mg/kg) were administered into the blood, peritoneal cavity, and subcutaneous tissue, or instilled into the lungs. The peptide was well tolerated at all subcutaneous and intraperitoneal doses, although higher levels were associated with delayed absorption kinetics and precipitation of the peptide within the tissues. Low intratracheal doses were rapidly absorbed systemically, and small increases in the dose level were lethal. Intravenous doses were rapidly cleared from the blood at lower levels, and upon escalation, were toxic with a high proportion of the dose accumulating within the lung tissue. To improve biocompatibility and prolong its circulation within the blood, IDR-1002 was further formulated onto high molecular weight hyperbranched polyglycerol (HPG) polymers. Constructs prepared at 5:1 and 10:1 peptide-to-polymer ratios were colloidally stable, maintained the biological profile of the peptide payload and helped reduce red blood cell lysis. The 5:1 construct circulated well in the blood, but higher peptide loading was associated with rapid clearance by the reticuloendothelial system. Many peptides face pharmacokinetic and biocompatibility challenges, but formulations such as those with HPG have the potential to overcome these limitations.

Prospective Study Comparing [99mTc]Tc-DP-FAPI Quantitative SPECT/CT with [68Ga]Ga-FAPI-04 PET/CT in Patients with Gastrointestinal Tumors.

Over the past decade, [68Ga]Ga-FAPI-04 positron emission tomography (PET)/CT imaging has been widely used for the treatment of various tumors. However, the application of 99mTC-labeled fibroblast activation protein inhibitors in tumors has been less studied. Our team previously demonstrated the safe biological distribution of [99mTc]Tc-DP-FAPI in the human body. Based on this, this study reports the accuracy of [99mTc]Tc-DP-FAPI in the imaging diagnosis of gastrointestinal tumors and compares it with that of [68Ga]Ga-FAPI-04 to evaluate the differences. A total of 24 patients with clinically diagnosed gastrointestinal tumors were prospectively included. All patients received [99mTc]Tc-DP-FAPI quantitative SPECT/CT imaging on the first day and [68Ga]Ga-FAPI-04 PET/CT imaging on the second day. And the effectiveness of the two imaging probes in detecting suspicious lesions was analyzed and compared. The primary tumors of all 24 patients were well detected by two imaging probes, and the sensitivity of [99mTc]Tc-DP-FAPI and [68Ga]Ga-FAPI-04 to the primary lesions was 100%. [99mTc]Tc-DP-FAPI examined 21 lymph nodes with a sensitivity and specificity of 32.8% and 10.9%, and [68Ga]Ga-FAPI-04 detected 57 lymph nodes with a sensitivity and specificity of 89.1% and 67.2%, respectively. Three distant metastases were detected by [99mTc]Tc-DP-FAPI and nine metastases by [68Ga]Ga-FAPI-04. The study showed that [99mTc]Tc-DP-FAPI is highly sensitive to detecting primary lesions of gastrointestinal tumors. Compared with [68Ga]Ga-FAPI-04, [99mTc]Tc-DP-FAPI has the same sensitivity in detecting primary tumors but has certain limitations in detecting metastases. [99mTc]Tc-DP-FAPI is of great value for preliminary screening of tumor lesions and early diagnosis of disease in patients who are suspected of having gastrointestinal tumors.

Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab')2.

Triggering receptor expressed on myeloid cells-2 (TREM2), which is expressed on the surface of tumor-associated macrophages (TAMs), has been found to play a major role in the diagnosis and treatment of tumors. TREM2 expression is significantly upregulated in tumor tissues, and therefore, targeting TREM2 for tumor imaging may be of value. Previously, we performed TREM2 targeting imaging by using 68Ga-NOTA-COG1410 or a 124I-labeled monoclonal antibody (mAb) and F(ab')2 in mouse models of colon and gastric tumors. However, some of the shortcomings of these probes (i.e., the high uptake of 68Ga-NOTA-COG1410 in the liver, the difficulty of obtaining iodine-124, and the long half-life of iodine-124) have hindered their clinical use. Herein, we sought to synthesize novel molecular probes targeting TREM2 that are more conducive to clinical translation, eliminating the interference of isotope availability and in vivo probe biodistribution issues. Therefore, we established A549 cell lines with negative human TREM2 (hTREM2) expression (GFP tag; hTREM2- A549) or upregulated hTREM2 expression (GFP tag; hTREM2+ A549) using lentiviral transfection and confirmed these with Western blotting and immunocytochemistry. We then prepared a mouse anti-human TREM2 (5-mAb) by immunizing with the hTREM2 antigen. The antibody fragments 5-F(ab')2 and 5-Fab were prepared from 5-mAb, and 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab were then synthesized with excellent stability and specificity. 99mTc-MAG3-5-F(ab')2 had a slightly higher in vitro affinity than 99mTc-MAG3-5-Fab (Kd = 3.32 ± 0.05 nmol versus 4.62 ± 0.85 nmol). 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab both showed excellent specificity: after adding a 100-fold precursor, the two probes binding to the cells were almost blocked. In vivo pharmacokinetics showed that the distribution and elimination half-lives of 99mTc-MAG3-5-Fab (T1/2α = 1.25 ± 0.30 min and T1/2ß = 21.98 ± 2.80 min, respectively) were significantly reduced compared to those of 99mTc-MAG3-5-F(ab')2 (T1/2α = 2.64 ± 0.37 min and T1/2ß = 86.55 ± 26.86 min, respectively). In micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, the tumor was clearly displayed at 1 h after 99mTc-MAG3-5-Fab injection, while the blood background was extremely low at 3 h, and the probe was mainly excreted through the kidneys and biliary tract. 99mTc-MAG3-5-F(ab')2 uptake was also detected at the tumor site, although the blood background was consistently high. The biodistribution results were consistent with the micro-SPECT/CT imaging results. 99mTc-MAG3-5-Fab could clearly display hTREM2+ A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Quantitative assessment of cardiac 123iodo-metaiodobenzylguanidine SPECT/CT in patients with arrhythmogenic right ventricular cardiomyopathy: Novel insight in disease monitoring.

BACKGROUND: The heart-to-mediastinum ratio (H/M-Ratio) of 123iodo-metaiodobenzylguanidine (123I-MIBG) represents state-of-the-art assessment for sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to evaluate quantitative reconstruction of 123I-MIBG uptake and to demonstrate its correlation with echocardiographic parameters. METHODS: Cardiac innervation was assessed in 23 patients diagnosed with definite ARVC or borderline ARVC and 12 patients with other cardiac disease presenting arrhythmia, using quantitative 123I-MIBG Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging. Tracer uptake was evaluated in the left (LV) and right ventricle (RV) based on a CT scan after quantitative image reconstruction. The relationship between tracer uptake and echocardiographic parameter data was examined. RESULTS: Absolute quantification of 123I-MIBG uptake in the LV and RV is feasible and correlates accurately with the gold standard H/M Ratio. When comparing sensitivity and specificity, the area under the curve (AUC) favors standardized uptake value (SUV) of the RV over the right-ventricle-to-mediastinum-ratio (RV/M-Ratio) for diagnosing ARVC. A reduced RV-SUV in patients with definite ARVC is associated with reduced RV function. RV polar maps revealed globally reduced 123I-MIBG uptake without segment-specific reduction in the RV. CONCLUSIONS: Quantitative 123I-MIBG SPECT in ARCV patients offers robust potential for clinical reporting and demonstrates a significant correlation with RV function. Segmental RV analysis needs to be evaluated in larger samples. In summary, cardiac 123I-MIBG imaging using SUV could facilitate image-guided therapy in patients diagnosed with ARVC.

Quantitative 99mTc-pyrophosphate myocardial uptake: Changes on transthyretin stabilization therapy.

BACKGROUND: Quantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography (99mTc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99mTc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function. METHODS: This prospective longitudinal cohort study investigated changes in 99mTc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVs) (SUVmax, SUVmean), cardiac amyloid activity (CAA; SUVmean∗LV activity volume), and percent injected dose (%ID) (mean activity concentration∗LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test. RESULTS: Following therapy, visual grade decreased significantly (P = 0.003). Several quantitative 99mTc-PYP metrics also decreased significantly: SUVmax (median -0.75, P = 0.011), CAA (median: -406.6, P < 0.001), and %ID (median: -0.45, P < 0.001). Serum transthyretin levels improved (median: +6.5 mg/dL, P = 0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, and LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable. CONCLUSIONS: Favorable changes in 99mTc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, whereas echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than amyloid burden regression. Further investigation is needed to understand the implications of these findings.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

SPECT/CT imaging of poor sleep quality in people with epilepsy.

PURPOSE: To analyze the characteristics of cerebral blood flow changes of poor sleep quality in people with epilepsy(PWE). METHODS: 90 PWE treated in The General Hospital of Ningxia Medical University from December 2021 to September 2023 were divided into poor sleep quality group (PSQG) and good sleep quality group (GSQG) according to the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), to compare the differences in cerebral perfusion between the two groups of patients, so as to summarize the characteristics of cerebral blood flow changes of poor sleep quality in PWE. RESULTS: The positive rate of interictal single-photon emission computed tomography/computed tomography (SPECT/CT) was 76.7 %(69/90), which showed localized cerebral hypoperfusion. There was no statistical difference between the two groups of PSQG (N=29) and GSQG (N=61) in terms of the positive rate of SPECT/CT, the number of hypoperfusion foci, and the range of hypoperfusion foci. In PSQG and GSQG, 9 patients(31.0 %) and 6 patients(9.8 %) showed hypoperfusion in the right parietal lobe, respectively, and the difference between the two groups was statistically significant (P=0.017). There was no statistical difference the rate of the interictal epileptiform discharges (IEDs) and the brain area of IEDs in electroencephalography(EEG) between the two groups. CONCLUSION: SPECT/CT of poor sleep quality in PWE demonstrated hypoperfusion in the right parietal lobe.

A general perspective for the conduct of radiolabelled distribution, metabolism, and excretion studies for antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of biopharmaceuticals that combine the specificity of monoclonal antibodies (mAbs) with the cytotoxicity of small molecule drugs. 15 ADCs have been approved by regulatory authorities up to now, mainly for indications in oncology, however, this review paper will only focus on the 13 ADCs that have been approved by either the FDA or EMA.ADME (Absorption, Distribution, Metabolism, and Excretion) studies are essential for the development of small molecule drugs to evaluate their disposition properties. These studies help to select drug candidates, determine the optimal dosing regimen and help to identify potential safety concerns for the drug of interest in human. Tissue distribution studies are also important as they facilitate the understanding of the efficacy and safety for parent drug and its metabolites in preclinical and clinical studies.For biologics, ADME studies are usually not required. In this paper, we review the existing approval packages and literature for approved ADCs to determine the extent of ADME studies performed as part of ADC registration packages.We conclude that ADME studies are recommended for the development of ADCs if new linkers and payloads are used that have never been used in humans before as these studies provide valuable information on the pharmacokinetic properties, optimal dosing regimen, and potential safety concerns. However, for the development of ADCs with established linker payload combinations, radiolabelled ADME studies may not be necessary if the distribution, metabolism and excretion properties have been described before. Clinical radiolabelled ADME studies are not recommended where patients are treated for life threating diseases like for indications in oncology.