Optimal Imaging Time Research Articles

Safety, Biodistribution, and Radiation Dosimetry of the 68Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors.

Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the 68Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH2 (68Ga-DOTA-MGS5). Methods: Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of 68Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. Results: The administration of 68Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. 68Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in 68Ga-DOTA-MGS5 PET/CT. Conclusion: Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for 68Ga-DOTA-MGS5.

Validation of Radiosynthesis and First in-Human Dosimetry of 68Ga-NOTA-UBI-29-41: A Proof of Concept Study.

Background: Antimicrobial peptides (AMPs) such as UBI-29-41 offer a distinctive approach for precise detection due to their unique interactions with bacteria and makes them promising candidates for specific and selective imaging. The study was aimed to corroborate the in-house manual synthesis of 68Ga-NOTA-UBI-29-41, evaluate its uptake in patients with suspected infection, and estimate of patient-specific dosimetry to ensure optimal clinical application. Materials and Methods: 68Ga-NOTA-UBI-29-41 was synthesized by using a variable amount of UBI-29-41 (60-90 μg) to 555 MBq of Ga-68 in 0.05 M Hydrochloric acid (HCl) and heating the reaction sample for 12 min at 90°C at pH: 3.5-4 to obtain the radiopeptide with high yield and high radiochemical purity (RCP). 68Ga-NOTA-UBI-29-41 positron emission tomography/Computed tomography (CT) scans at variable timepoints were done to evaluate its biodistribution and maximum uptake time. Furthermore, patient-specific dosimetric estimation was done using the HERMES software. Results: A total of 5 μg/37 MBq (5 μg/mCi) of NOTA-UBI-29-41 for 12 min at 90°C were the optimal parameters to obtain 88%-90% of yield and 98%-99 % of RCP. 68Ga-NOTA-UBI-29-41 showed expeditious blood clearance and high renal excretion. The optimal time for imaging of infection with 68Ga-NOTA-UBI-29-41 was found to be at 60 min postinjection (n = 8). The critical organ was the urinary bladder, receiving an average dose of 138.02 ± 45.92 µSv/MBq, followed by 53.81 ± 13.72 µSv/MBq for kidneys with a mean effective dose of 1.52 ± 0.64 mSv. Conclusion: The protocol for in-house manual labeling of 68Ga-NOTA-UBI-29-41 was reproducible, providing high yield and RCP. 68Ga-NOTA-UBI-29-41 administration was found to be safe and nontoxic. The favorable biodistribution and the first-in-human patient-specific dosimetry ensure optimal clinical application.

Optimization of image shoot timing for cerebral veins 3D-digital subtraction angiography by interventional angiography systems

Abstract3D-digital subtraction angiography (3D-DSA) is essential for understanding the anatomical structure of cerebral veins, crucial in brain tumor surgery. 3D-DSA produces three-dimensional images of veins by adjusting the X-ray delay time after contrast agent injection, but the delineation of veins varies with the delay in X-ray timing. Our study aimed to refine the delay time using time-enhancement curve (TEC) analysis from 2D-DSA conducted before 3D-DSA imaging. We retrospectively reviewed 26 meningioma patients who underwent cerebral angiography from March 2020 to August 2021. Using 2D-DSA, we analyzed arterial and venous TECs to determine the contrast agent’s peak time and estimated the optimal imaging timing. Cases performed near this optimal time were in Group A, and others in Group B, with cerebral venous pixel values compared between them. TEC analysis identified peak times: internal carotid artery: 2.8 ± 0.7 s, middle cerebral artery (M4): 4.1 ± 0.9 s, superior sagittal sinus: 8.3 ± 1.1 s, sigmoid sinus: 9.5 ± 1.3 s, and venous structures near tumors: 7.3 ± 1.0 s. We observed several veins peaking immediately after arterial contrast passage, suggesting the optimal X-ray delay should incorporate the arterial contrast agent’s transit time. Statistical analysis revealed that Group A, with imaging timed to reflect the contrast agent transit time, demonstrated significantly better contrast effects than Group B. The X-ray delay time for 3D-DSA imaging of cerebral veins can be optimized in angiography systems by incorporating the contrast agent transit time, calculated from TEC analysis of cerebral 2D-DSA images.

First‐in‐human orbital tumor surgery guided by near‐infrared II window fluorescence imaging: A feasibility study

AbstractPrecise resection of orbital tumors is a critically important but elusive issue. Fluorescence imaging in the near‐infrared II window (NIR‐II) holds the potential to provide the surgeons with real‐time identification for orbital tumors. Here, for the first time, we evaluated the feasibility and clinical value of NIR‐II fluorescence imaging in orbital tumor surgery. To establish the method of NIR‐II fluorescence imaging for orbital tumors, we developed a NIR‐II fluorescence imaging system and indocyanine green (ICG) served as the fluorescent contrast agent. Twenty‐two patients diagnosed with orbital tumors and scheduled for standard‐of‐care surgery were enrolled in this study. Time‐course NIR‐II fluorescence imaging of two patients with superficial orbital tumors showed the optimum imaging time was 2 h post injection of ICG. Fifteen patients were allocated for diagnostic test, which showed that both the in situ and ex vivo NIR‐II fluorescence imaging showed better sensitivity and specificity than the surgeon judgment. In the feasibility trial of the remaining five patients, the surgeon encountered 34 suspicious regions and surgical decisions were changed nine times due to NIR‐II fluorescence imaging. The resultant seven additional resections were justified by histopathology and the two conservative treatments did not result in recurrence. Based on these findings, we suggested that ICG‐based NIR‐II fluorescence imaging was feasible to guide precise resection of orbital tumors. A future randomized controlled trial with a larger cohort is encouraged to further verify the clinical value.

Simplified dual-time-point 99mTc-pyrophosphate scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy: A single center series

Background There is a lack of consensus regarding the optimal imaging time points and imaging techniques between planar and/or single-photon emission computed tomography (SPECT)/computed tomography (CT) acquisitions for technetium-99 m pyrophosphate (99mTc-PYP) cardiac scintigraphy. The aim of this study was to investigate correlations between planar and SPECT/CT images and between 1-h and 3-h imaging time points. Methods We retrospectively analyzed consecutive patients with clinically suspected transthyretin amyloid cardiomyopathy who underwent 99mTc-PYP scintigraphy from November 1, 2019 to November 30, 2022. Visual scores were compared between 1- and 3-h imaging time points and between planar and SPECT/CT acquisitions. Results A total of 100 patients (66% male; mean age, 65 years) were included, and 1- and 3-h planar and SPECT/CT images were obtained for 97 patients. There was a significant difference in visual grading scores between 1- and 3-h time points on both planar and SPECT/CT imaging, with a downgrade in score in 61 of 99 (61%) cases on planar imaging, and in 14 of 97 (14%) cases on SPECT/CT imaging (p < 0.001). There were significant differences in visual grading scores between planar and SPECT/CT imaging at both time points, with cases being scored higher on planar imaging than on SPECT/CT imaging (81/97 cases for 1-h imaging, and 50/97 cases for 3-h imaging) (p < 0.001). Conclusion Simplified 1-h SPECT/CT imaging with visual score and selective use of 3-h SPECT/CT imaging may be an efficient protocol and may reduce the potential for over-scoring and equivocal interpretation. Further validation in larger and more diverse populations is needed.

The Optimal Time for Postoperative Magnetic Resonance Imaging of the Sella in Patients With Pituitary Adenoma

The Optimal Time for Postoperative Magnetic Resonance Imaging of the Sella in Patients With Pituitary Adenoma

Timing of ultra-portable ultrasound (UPUS) Examinations in detecting clinically concerning recurrent pneumothorax

BackgroundRecurrent pneumothorax (rPTX) is a common complication following thoracostomy tube (TT) removal in chest trauma patients. While chest X-ray (CXR) is most commonly used to detect a rPTX, bedside ultraportable ultrasound (UPUS) is a feasible, low cost, and radiation free alternative. No consensus exists with regards to the optimal timing of diagnostic imaging to assess for rPTX post-TT removal. Accordingly, we sought to identify an ideal UPUS timing to detect a rPTX MethodsWe conducted a single center prospective study of adult (≥18years) patients admitted with a chest trauma. UPUS examinations were performed using the Butterfly iQ+™ ultrasound. Three intercostal spaces (ICS) were evaluated (2nd through 4th). Post-TT UPUS examinations were performed at different timepoints following tube removal (1–6 h). A rPTX on UPUS was defined as the absence of lung-sliding in one or more intercostal spaces, and was considered a clinically concerning rPTX if lung-sliding was absent in ≥2 ICS. UPUS findings were compared to CXR. ResultsNinety-two patients (97 hemi-thoraces) were included in the analysis. A total of 58 patients had a post-TT removal rPTX of which 11 were either clinically concerning or expanding. Comparing UPUS findings to CXR, the 3-hour post-TT removal ultrasound examinations were associated with the highest sensitivity. By hour 4, no rPTX showed expansion in size. Three patients required an intervention for a clinically concerning rPTX, all of whom were detected on UPUS 3-hour post-TT removal. ConclusionBedside UPUS performed at 3-hour post-TT removal has the highest sensitivity in detecting clinically concerning rPTX. Size of rPTX appears to stabilize by hour 4. In the absence of clinical symptoms, repeat imaging or observation of non-significant rPTX beyond 4 h may not provide added clinical benefit. Level of EvidenceLevel II, Diagnostic Tests or Criteria

Enhanced tumor targeting and penetration of fluorophores via iRGD peptide conjugation: a strategy for the precision targeting of lung cancer.

Accurate real-time tumor delineation is essential for achieving curative resection (R0 resection) during non-small cell lung cancer (NSCLC) surgery. The unique characteristics of lung tissue structure significantly challenge the use of video-assisted thoracoscopic surgery in the identification of lung nodules. This difficulty often results in an inability to discern the margins of lung nodules, necessitating either an expansion of the resection scope, or a transition to open surgery. Due to its high spatial resolution, ease of operation, and capacity for real-time observation, near-infrared fluorescence (NIRF) navigation in oncological surgery has emerged as a focal point of clinical research. Targeted NIRF probes, which accumulate preferentially in tumor tissues and are rapidly cleared from normal tissues, enhance diagnostic sensitivity and surgical outcomes. The imaging effect of the clinically approved NIRF probe indocyanine green (ICG) varies significantly from person to person. Therefore, we hope to develop a new generation of targeted NIRF probes targeting lung tumor-specific targets. First, the peptide iRGD (sequence: CRGDKGPDC) fluorescent tracer was synthesized, and characterized through mass spectrometry (MS), proton nuclear magnetic resonance (1H NMR), and high-performance liquid chromatography (HPLC). Fluorescence properties were tested subsequently. Safety was performed in vitro using both human normal liver cells and human normal breast cells. Second, Metabolism and optimal imaging time were determined by tail vein injection of iRGD fluorescent tracer. Finally, Orthotopic and metastatic lung tumor models were used to evaluate the targeting properties of the iRGD fluorescent tracer. We successfully synthesized an iRGD fluorescent tracer specifically designed to target NSCLC. The molecular docking analyses indicated that this tracer has receptor affinity comparable to that of iRGD for αvβ3 integrin, with a purity ≥98%. Additionally, the tracer is highly soluble in water, and its excitation and emission wavelengths are 767 and 799 nm, respectively, positioning it within the near-infrared spectrum. The cellular assays confirmed the tracer's minimal cytotoxicity, underscoring its excellent biosafety profile. In vivo studies further validated the tracer's capacity for specific NSCLC detection at the cellular level, alongside a prolonged imaging window of 6 days or more. Notably, the tracer demonstrated superior specificity in localizing very small lung nodules, which are otherwise clinically indiscernible, outperforming non-targeted ICG. Fluorescence intensity analyses across various organs revealed that the tracer is predominantly metabolized by the liver and kidneys, with excretion via bile and urine, and exhibits minimal toxicity to these organs as well as the lungs. The iRGD fluorescent tracer selectively accumulates in NSCLC tissues by specifically targeting αvβ3 receptors, which are overexpressed on the surface of tumor cells. This targeted approach facilitates the real-time intraoperative localization of NSCLC, presenting an improved strategy for intraoperative tumor identification with significant potential for clinical application.

Advancing Cancer Theranostics Through Integrin αVβ3-Targeted Peptidomimetic IAC: From Bench to Bedside.

Introduction: The expression of alpha-five beta-three (αVβ3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVβ3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2',2"-{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [68Ga]Ga, [177Lu]Lu, and [225Ac]Ac was optimized. The binding affinity (Kd) of DOTAGA-IAC for the αVβ3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [177Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [68Ga]Ga-DOTAGA-IAC and [18F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [68Ga]Ga-DOTAGA-IAC and [18F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). Kd and Bmax measurements were 15.02 nM and 417 fmol for αVβ3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [177Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30-35 mins postadministration. Out of the cohort, [68Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUVmax) of 3.94 ± 0.58 compared with [18F]FDG (SUVmax 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVβ3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [68Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVβ3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy.

Impact of the Reference Multiple-Time-Point Dosimetry Protocol on the Validity of Single-Time-Point Dosimetry for [177Lu]Lu-PSMA-I&T Therapy.

Internal dosimetry supports safe and effective patient management during radionuclide therapy. Yet, it is associated with high clinical workload, costs, and patient burden, as patient scans at multiple time points (MTPs) must be acquired. Dosimetry based on imaging at a single time point (STP) has continuously gained popularity. However, MTP protocols, used as a reference to judge the validity of STP dosimetry, differ depending on local requirements and deviate from the unknown patient-specific ground truth pharmacokinetics. The aim of this study was to compare the error and optimum time point for different STP approaches using different reference MTP protocols. Methods: Whole-body SPECT/CT scans of 7 patients (7.4-8.9 GBq of [177Lu]Lu-PSMA-I&T) were scheduled at 24, 48, 72, and 168 h after injection. Sixty lesions, 14 kidneys, and 10 submandibular glands were delineated in the SPECT/CT data. Two curve models, that is, a mono- and a biexponential model, were fitted to the MTP data, in accordance with goodness-of-fit analysis (coefficients of variation, sum of squared errors). Three population-based STP approaches were compared: one method published by Hänscheid etal., one by Jackson etal., and one using population-based effective half-lives in the mono- or biexponential curve models. Percentage differences between STP and MTP dosimetry were evaluated. Results: Goodness-of-fit parameters show that a monoexponential function and a biexponential function with shared population-based parameters and physical tail are reasonable reference models. When comparing both reference models, we observed maximum differences of -44%, -19%, and -28% in the estimated absorbed doses for lesions, kidneys, and salivary glands, respectively. STP dosimetry with an average deviation of less than 10% from MTP dosimetry may be feasible; however, this deviation and the optimum imaging time point showed a dependence on the chosen reference protocol. Conclusion: STP dosimetry for [177Lu]Lu-PSMA therapy is promising to boost the integration of dosimetry into clinical routine. According to our patient cohort, 48 h after injection may be regarded as a compromise for STP dosimetry for lesions and at-risk organs. The results from this analysis show that a common gold standard for dosimetry is desirable to allow for reliable and comparable STP dosimetry.

Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal 18F-Labeled PET Probes Specifically Targeting Estrogen Receptor α.

The estrogen receptor α positive (ERα+) subtype represents nearly 70% of all breast cancers (BCs), which seriously threaten women's health. Positron emission computed tomography (PET) characterizes its superiority in detecting the recurrence and metastasis of BC. In this article, an array of novel PET probes ([18F]R-1, [18F]R-2, [18F]R-3, and [18F]R-4) targeting ERα based on the tetrahydropyridinyl indole scaffold were developed. Among them, [18F]R-3 and [18F]R-4 showed good target specificity toward ERα and could distinguish MCF-7 (ERα+) and MDA-MB-231 (ERα-) tumors efficiently. Especially, [18F]R-3 could differentiate the ERα positive/negative tumors successfully with a higher tumor-to-muscle uptake ratio (T/M) than that of [18F]R-4. The radioactivity of [18F]R-3 in the MCF-7 tumor was 5.24 ± 0.84%ID/mL and its T/M ratio was 2.49 ± 0.62 at 25 min postinjection, which might be the optimal imaging time point in PET scanning. On the contrary, [18F]R-3 did not accumulate in the MDA-MB-231 tumor at all. The autoradiography analysis of [18F]R-3 on the MCF-7 tumor-bearing mice model was consistent with the PET imaging results. [18F]R-3 exhibited the pharmacokinetic property of rapid distribution and slow clearance, making it suitable for use as a diagnostic PET probe. Overall, [18F]R-3 was capable of serving as a PET radiotracer to delineate the ERα+ tumor and was worthy of further exploitation.

The Usefulness of Posterior Shiny Corner Lesions in the Early Diagnosis of Medial Meniscus Posterior Root Tears.

Posterior shiny corner lesions (PSCLs) have been reported to be useful for the early diagnosis of medial meniscus posterior root tears (MMPRTs) in surgical patients. However, the usefulness of PSCLs in outpatients, particularly regarding the optimal timing of magnetic resonance imaging (MRI) examinations after injury, remains unknown. We hypothesized that PSCLs would normally be observed in patients with MMPRTs within one month of injury. This study included 144 patients with knee pain who visited our hospital between January 2021 and May 2023. MRI findings within and after one month were examined. Fisher's exact test was performed for PSCLs, cleft signs, ghost signs, radial tear signs, bone cysts, and medial meniscus extrusion (MME), which are findings used for the diagnosis of MMPRTs. Time-dependent receiver operating characteristic (ROC) curve analysis was performed for each MRI finding. A binomial logistic regression analysis was performed for age, sex, PSCL, ghost sign, and MME. PSCLs were observed on 82.6% of the MRI scans within one month, but the positivity rate decreased after one month. After one month, a high percentage of patients had cleft signs and ghost signs. The results of a time-dependent ROC curve analysis showed that the PSCL had better diagnostic ability than the cleft sign, ghost sign, radial tear sign, and MME at a relatively early stage. Additionally, the area under the curve (AUC) of PSCL peaks around 35 days and then declines, reaching 0.8 or less around 40 days. On the other hand, the AUC of the cleft sign and ghost sign began to increase around 30 days after injury, and it exceeded 0.8 after approximately 100 days. The results of the binomial logistic regression analysis revealed significant PSCLs and ghost signs. Independent associations between the PSCL, or ghost sign, and the MMPRT were demonstrated. This study suggests that PSCLs have a superior diagnostic capability for MMPRT during the early stages of injury compared with other MRI findings in outpatients. In particular, PSCLs have a high positivity rate within one month after injury and a high diagnostic capacity up to 40 days after injury.

High-success-rate ISAR imaging of maneuvering targets with a robust optimal imaging time interval selection algorithm

High-success-rate ISAR imaging of maneuvering targets with a robust optimal imaging time interval selection algorithm

Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7). The ZD2-Gd-DOTA-Cy7 probe was constructed by conjugating a peptide (Cys-TVRTSAD) to Gd-DOTA and the near-infrared dye Cy7. PDAC murine xenograft models were intravenously injected with ZD2-Gd-DOTA-Cy7 at a Gd concentration of 0.05 mmol/kg or free Cy7 and Gd-DOTA as control. The normalized tumor background ratio (TBR) on FMI and the T1 reduction ratio on MRI were quantitatively analyzed. For models receiving AG chemotherapy or saline, MRI/FMI was performed before and after treatment. Histological analyses were performed for validation. The ZD2-Gd-DOTA-Cy7 concentration showed a linear correlation with the fluorescence intensity and T1 relaxation time in vitro. The optimal imaging time was 30min after injection of the ZD2-Gd-DOTA-Cy7 (0.05 mmol/kg), only half of the clinic dosage of gadolinium. Additionally, ZD2-Gd-DOTA-Cy7 generated a 1.44-fold and 1.90-fold robust contrast enhancement compared with Cy7 (P < 0.05) and Gd-DOTA (P < 0.05), respectively. For AG chemotherapy monitoring, the T1 reduction ratio and normalized TBR in the fibrotic tumor areas were significantly increased by 1.99-fold (P < 0.05) and 1.78-fold (P < 0.05), respectively, in the control group compared with those in the AG group. MRI/FMI with a low dose of ZD2-Gd-DOTA-Cy7 enables sensitive imaging of PDAC and the quantitative assessment of fibrotic changes during AG chemotherapy, which shows potential clinical applications for precise diagnosis, post-treatment monitoring, and disease management.

Advances and challenges in immunoPET methodology.

Immuno-positron emission tomography (immunoPET) enables imaging of specific targets that play a role in targeted therapy and immunotherapy, such as antigens on cell membranes, targets in the disease microenvironment, or immune cells. The most common immunoPET applications use a monoclonal antibody labeled with a relatively long-lived positron emitter such as 89Zr (T 1/2 = 78.4 h), but smaller antibody-based constructs labeled with various other positron emitting radionuclides are also being investigated. This molecular imaging technique can thus guide the development of new drugs and may have a pivotal role in selecting patients for a particular therapy. In early phase immunoPET trials, multiple imaging time points are used to examine the time-dependent biodistribution and to determine the optimal imaging time point, which may be several days after tracer injection due to the slow kinetics of larger molecules. Once this has been established, usually only one static scan is performed and semi-quantitative values are reported. However, total PET uptake of a tracer is the sum of specific and nonspecific uptake. In addition, uptake may be affected by other factors such as perfusion, pre-/co-administration of the unlabeled molecule, and the treatment schedule. This article reviews imaging methodologies used in immunoPET studies and is divided into two parts. The first part summarizes the vast majority of clinical immunoPET studies applying semi-quantitative methodologies. The second part focuses on a handful of studies applying pharmacokinetic models and includes preclinical and simulation studies. Finally, the potential and challenges of immunoPET quantification methodologies are discussed within the context of the recent technological advancements provided by long axial field of view PET/CT scanners.

First-in-Human Evaluation of Site-Specifically Labeled 89Zr-Pertuzumab in Patients with HER2-Positive Breast Cancer.

Radioimmunoconjugates targeting human epidermal growth factor receptor 2 (HER2) have shown potential to noninvasively visualize HER2-positive tumors. However, the stochastic approach that has been traditionally used to radiolabel these antibodies yields poorly defined and heterogeneous products with suboptimal invivo performance. Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry of 89Zr-site-specific (ss)-pertuzumab PET, a site-specifically labeled radioimmunoconjugate designed to circumvent the limitations of random stochastic lysine labeling. Methods: Six patients with HER2-positive metastatic breast cancer were enrolled in a prospective clinical trial. Pertuzumab was site-specifically modified with desferrioxamine (DFO) via a novel chemoenzymatic strategy and subsequently labeled with 89Zr. Patients were administered 74 MBq of 89Zr-ss-pertuzumab in 20 mg of total antibody intravenously and underwent PET/CT at 1 d, 3-4 d, and 5-8 d after injection. PET imaging, whole-body probe counts, and blood draws were performed to assess the pharmacokinetics, biodistribution, and dosimetry. Results: 89Zr-ss-pertuzumab PET/CT was used to assess HER2 status and heterogeneity to guide biopsy and decide the next line of treatment at progression. The radioimmunoconjugate was able to detect known sites of malignancy, suggesting that these tumor lesions were HER2-positive. The optimal imaging time point was 5-8 d after administration, and no toxicities were observed. Dosimetry estimates from OLINDA showed that the organs receiving the highest doses (mean ± SD) were kidney (1.8 ± 0.5 mGy/MBq), liver (1.7 ± 0.3 mGy/MBq), and heart wall (1.2 ± 0.1 mGy/MBq). The average effective dose for 89Zr-ss-pertuzumab was 0.54 ± 0.03 mSv/MBq, which was comparable to both stochastically lysine-labeled 89Zr-DFO-pertuzumab and 89Zr-DFO-trastuzumab. One patient underwent PET/CT with both 89Zr-ss-pertuzumab and 89Zr-DFO-pertuzumab 1 mo apart, with 89Zr-ss-pertuzumab demonstrating improved lesion detection and higher tracer avidity. Conclusion: This study demonstrated the safety, dosimetry, and potential clinical applications of 89Zr-ss-pertuzumab PET/CT. 89Zr-ss-pertuzumab may detect more lesions than 89Zr-DFO-pertuzumab. Potential clinical applications include real-time evaluation of HER2 status to guide biopsy and assist in treatment decisions.

Identification of the Vulnerability of Atherosclerotic Plaques by a Photoacoustic/Ultrasonic Dual-Modal cRGD Nanomolecular Probe.

To explore the feasibility of using cRGD-GNR-PFP-NPs to assess plaque vulnerability in an atherosclerotic plaque mouse model by dual-modal photoacoustic/ultrasonic imaging. A nanomolecular probe containing gold nanorods (GNRs) and perfluoropentane (PFP) coated with the cyclic Arg-Gly-Asp (cRGD) peptide were prepared by double emulsion solvent evaporation and carbodiimide methods. The morphology, particle size, potential, cRGD conjugation and absorption features of the nanomolecular probe were characterized, along with its in vitro phase transformation and photoacoustic/ultrasonic dual-modal imaging properties. In vivo fluorescence imaging was used to determine the distribution of cRGD-GNR-PFP-NPs in vivo in apolipoprotein E-deficient (ApoE-/-) atherosclerotic plaque model mice, the optimal imaging time was determined, and photoacoustic/ultrasonic dual-modal molecular imaging of integrin αvβ3 expressed in atherosclerotic plaques was performed. Pathological assessments verified the imaging results in terms of integrin αvβ3 expression and plaque vulnerability. cRGD-GNR-PFP-NPs were spherical with an appropriate particle size (average of approximately 258.03±6.75 nm), a uniform dispersion, and a potential of approximately -9.36±0.53 mV. The probe had a characteristic absorption peak at 780~790 nm, and the surface conjugation of the cRGD peptide reached 92.79%. cRGD-GNR-PFP-NPs were very stable in the non-excited state but very easily underwent phase transformation under low-intensity focused ultrasound (LIFU) and had excellent photoacoustic/ultrasonic dual-modal imaging capability. Mice fed a high-fat diet for 20 weeks had obvious hyperlipidemia with larger, more vulnerable plaques. These plaques could be specifically targeted by cRGD-GNR-PFP-NPs as determined by in vivo fluorescence imaging, and the enrichment of nanomolecular probe increased with the increasing of plaque vulnerability; the photoacoustic/ultrasound signals of the plaques in the high-fat group were stronger. The pathological assessments were in good agreement with the cRGD-GNR-PFP-NPs plaque accumulation, integrin αvβ3 expression and plaque vulnerability results. A phase variant photoacoustic/ultrasonic dual-modal cRGD nanomolecular probe was successfully prepared and can be used to identify plaque vulnerability safely and effectively.

Bio-distribution study of Tc-99m HMPAO labeled platelet in healthy volunteer.

The bio-distribution of Tc-99m HMPAO labeled platelets (LP), which could be used to image subtle thrombosis, is not reported in a human yet, which is the subject of the current study. The platelets were extracted from 49 ml whole blood and labeled with Tc-99m HMPAO, then re-injected to the healthy volunteer. Anterior and posterior whole body imaging was done by a dual-head gamma camera 3, 18, 33, 46, 81, 124, 190 min and 15 hours after injection. Also a whole-body SPECT was done at 137 min post-injection. The area under the curves of the spleen, liver, left kidney, bladder, right lung, brain, and abdominal aorta ROIs was calculated to estimate the accumulation of labeled platelets within the organs. The spleen was the target organ. The kidneys, liver, and heart were also remarkably visualized. The thyroid, stomach, bladder, or gastrointestinal (GI) uptake/activity was not significant. The stomach visualization was enhanced after ingestion at 60 min. The sagittal and lateral sinuses were delineated, and the background of the brain was very low. During the study, the area under the curve of activity was 738, 308, 302, 196, 230, 121, 79, 216, 529, 369, 162, and 54 counts. min/pixel for spleen, liver, heart, right lung, left kidney, right iliac artery, sagittal sinus, thyroid, bladder, stomach, GI, and background, respectively. The quality of the scan with low dose Tc-99m HMPAO LPs is optimal. We documented the bio-distribution of LPs. The optimal imaging time was 80-120 min post-injection when the free Tc-99m and GI transit were negligible. The sagittal and lateral sinuses were visualized enabling detection of possible clots in the vessels.

The Optimal Time for Postoperative Magnetic Resonance Imaging of the Sella in Patients With Pituitary Adenoma

The Optimal Time for Postoperative Magnetic Resonance Imaging of the Sella in Patients With Pituitary Adenoma

Development of a fibroblast activation protein-targeted PET/NIR dual-modality probe and its application in head and neck cancer.

Purpose: The combination of near-infrared (NIR) and positron emission tomography (PET) imaging presents an opportunity to utilize the benefits of dual-modality imaging for tumor visualization. Based on the observation that fibroblast activation protein (FAP) is upregulated in cancer-associated fibroblasts (CAFs) infiltrating all solid tumors, including head and neck squamous cell carcinoma (HNSCC), we developed the novel PET/NIR probe [68Ga]Ga-FAP-2286-ICG. Preclinically, the specificity, biodistribution and diagnostic properties were evaluated. Methods: Cell uptake assays were completed with the U87MG cell to evaluate the specificity of the [68Ga]Ga-FAP-2286-ICG. The tumor-targeting efficiency, biodistribution and optimal imaging time window of the [68Ga]Ga-FAP-2286-ICG were studied in mice bearing U87MG xenografts. HNSCC tumor-bearing mice were used to evaluate the feasibility of [68Ga]Ga-FAP-2286-ICG for tumor localization and guided surgical resection of HNSCC tumors. Results: The in vitro experiments confirmed that [68Ga]Ga-FAP-2286-ICG showed good stability, specific targeting of the probe to FAP, and the durable retention effect in high-expressing FAP tumors U87MGcell. Good imaging properties such as good tumor uptake, high tumor-to-background ratios (5.44 ± 0.74) and specificity, and tumor contouring were confirmed in studies with mice bearing the U87MG xenograft. PET/CT imaging of the probe in head and neck cancer-bearing mice demonstrated specific uptake of the probe in the tumor with a clear background. Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions. Conclusion: In a preclinical model, these attractive [68Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation.