Predictive significance of intraprostatic volumetric parameters derived from early and standard time 68Ga-PSMA PET/CT images in newly diagnosed prostate cancer patients.

OBJECTIVE: To investigate the relationship between intraprostatic 68Ga-prostate-specific membrane antigen (PSMA) uptake values and volumetric parameters derived from early pelvic and standard-time whole-body 68Ga-PSMA PET/computed tomography (CT) images in untreated prostate cancer (PCa) patients, and to assess the predictive significance of these data in relation to disease prognosis, comparing them with the Gleason score, clinical risk classification and the presence of metastatic disease detected in 68Ga-PSMA PET/CT imaging. METHODS: Eighty-one newly diagnosed PCa patients underwent early phase pelvic imaging at the 5th minute and standard time whole-body imaging at the 60th minute. Various threshold values were used in intraprostatic delineations to compute maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), intraprostatic PSMA tumor volume and intraprostatic total lesion PSMA uptake. Correlations between early and standard time measurements, as well as changes in SUV parameters over time, were examined. The association of these values with Gleason score, clinical risk status (National Comprehensive Cancer Network), and metastatic disease was explored. RESULTS: SUVmax measurements from both early and standard time images distinguished all three groups (clinical risk scores, Gleason score and metastatic group), with standard imaging demonstrating statistical superiority in receiver operating characteristic analyses. Strong correlations were observed between early and standard-time PET parameters. Changes in intraprostatic SUVmax and SUVmean values over time did not exhibit predictive value. CONCLUSION: Although intraprostatic PSMA PET parameters generally aligned at both early and standard times, parameters obtained from standard time images showed more robust correlations with clinical risk scores, Gleason score and metastasis status in newly diagnosed, untreated PCa patients.

68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG.

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of 68Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with 18F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of 68Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with 68Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUVmax was significantly higher on 68Ga-FAP-2286 PET than on 18F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: 68Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,68Ga-FAP-2286 PET had consistently higher uptake than 18F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.

Bilateral Adrenal Metastasis of Prostatic Adenocarcinoma on 68 Ga-PSMA PET/CT Imaging.

ABSTRACT: An 84-year-old man with prostate adenocarcinoma underwent 68 Ga-PSMA PET/CT due to PSA recurrence. Foci of 68 Ga-PSMA uptake were observed in bilateral adrenal glands. Adrenal MRI showed metastasis only in the left adrenal gland. Metastatic 68 Ga-PSMA uptake was also observed in the mediastinum and bone. Enzalutamide treatment was started. Follow-up 68 Ga-PSMA PET/CT scan showed regression in both adrenal gland metastases and other metastases.

Intramuscular Granular Cell Tumor Detected on 68 Ga-PSMA PET/CT.

ABSTRACT: Finding of the prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PC) cells that have made it possible to evaluate the patients with PC with a single imaging method. 68 Ga-PSMA PET/CT is now part of the routine in patients with PC. After several years of clinical experience with PSMA tracers, the specificity is satisfactory; however, concerns about the specificity are raising day by day due to the newly laid out nonprostatic malignant and benign lesions with high PSMA expression. Herein, we present an incidental 68 Ga-PSMA uptake in an intramuscular granular cell tumor.

Hepatic PSMA-Avid Postradiation Inflammation.

ABSTRACT: A 62-year-old man with de novo large volume metastatic prostate cancer to the bone, liver, and nodes status post multiple lines of therapy including external beam radiation to T12-L2 approximately 13 months prior underwent 68 Ga-PSMA PET/CT to determine eligibility for 177 Lu-PSMA therapy. 68 Ga-PSMA PET/CT demonstrated tracer-avid osseous and nodal lesions consistent with metastases. In addition, regional geographic tracer avidity was seen in the midline left hepatic lobe associated with capsular retraction and demonstrated no FDG avidity on subsequent imaging, probably inflammatory related to prior radiation to T12-L2.

68Ga-Fibroblast Activation Protein Inhibitor PET/CT Improves Detection of Intermediate and Low-Grade Sarcomas and Identifies Candidates for Radiopharmaceutical Therapy.

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of 68Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown. We assessed the diagnostic performance and accuracy of 68Ga-FAPI PET in various bone and soft-tissue sarcomas. Potential eligibility for FAP-targeted radiopharmaceutical therapy (FAP-RPT) was evaluated. Methods: This prospective observational trial enrolled 200 patients with bone and soft-tissue sarcoma who underwent 68Ga-FAPI PET/CT and 18F-FDG PET/CT (186/200, or 93%) for staging or restaging. The number of lesions detected and the uptake (SUVmax) of the primary tumor, lymph nodes, and visceral and bone metastases were analyzed. The Wilcoxon test was used for semiquantitative assessment. The association of 68Ga-FAPI uptake intensity, histopathologic grade, and FAP expression in sarcoma biopsy samples was analyzed using Spearman r correlation. The impact of 68Ga-FAPI PET on clinical management was investigated using questionnaires before and after PET/CT. Eligibility for FAP-RPT was defined by an SUVmax greater than 10 for all tumor regions. Results: 68Ga-FAPI uptake was heterogeneous among sarcoma subtypes. The 3 sarcoma entities with the highest uptake (mean SUVmax ± SD) were solitary fibrous tumor (24.7 ± 11.9), undifferentiated pleomorphic sarcoma (18.8 ± 13.1), and leiomyosarcoma (15.2 ± 10.2). Uptake of 68Ga-FAPI versus 18F-FDG was significantly higher in low-grade sarcomas (10.4 ± 8.5 vs. 7.0 ± 4.5, P = 0.01) and in potentially malignant intermediate or unpredictable sarcomas without a World Health Organization grade (not applicable [NA]; 22.3 ± 12.5 vs. 8.5 ± 10.0, P = 0.0004), including solitary fibrous tumor. The accuracy, as well as the detection rates, of 68Ga-FAPI was higher than that of 18F-FDG in low-grade sarcomas (accuracy, 92.2 vs. 80.0) and NA sarcomas (accuracy, 96.9 vs. 81.9). 68Ga-FAPI uptake and the histopathologic FAP expression score (n = 89) were moderately correlated (Spearman r = 0.43, P < 0.0002). Of 138 patients, 62 (45%) with metastatic sarcoma were eligible for FAP-RPT. Conclusion: In patients with low-grade and NA sarcomas, 68Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18F-FDG PET. 68Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.

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.

Comparison of quantitative whole body PET parameters on [68Ga]Ga-PSMA-11 PET/CT using ordered Subset Expectation Maximization (OSEM) vs. bayesian penalized likelihood (BPL) reconstruction algorithms in men with metastatic castration-resistant prostate cancer.

BACKGROUND: PSMA PET/CT is a predictive and prognostic biomarker for determining response to [177Lu]Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer (mCRPC). Thresholds defined to date may not be generalizable to newer image reconstruction algorithms. Bayesian penalized likelihood (BPL) reconstruction algorithm is a novel reconstruction algorithm that may improve contrast whilst preventing introduction of image noise. The aim of this study is to compare the quantitative parameters obtained using BPL and the Ordered Subset Expectation Maximization (OSEM) reconstruction algorithms. METHODS: Fifty consecutive patients with mCRPC who underwent [68Ga]Ga-PSMA-11 PET/CT using OSEM reconstruction to assess suitability for [177Lu]Lu-PSMA-617 therapy were selected. BPL algorithm was then used retrospectively to reconstruct the same PET raw data. Quantitative and volumetric measurements such as tumour standardised uptake value (SUV)max, SUVmean and Molecular Tumour Volume (MTV-PSMA) were calculated on both reconstruction methods. Results were compared (Bland-Altman, Pearson correlation coefficient) including subgroups with low and high-volume disease burdens (MTV-PSMA cut-off 40 mL). RESULTS: The SUVmax and SUVmean were higher, and MTV-PSMA was lower in the BPL reconstructed images compared to the OSEM group, with a mean difference of 8.4 (17.5%), 0.7 (8.2%) and - 21.5 mL (-3.4%), respectively. There was a strong correlation between the calculated SUVmax, SUVmean, and MTV-PSMA values in the OSEM and BPL reconstructed images (Pearson r values of 0.98, 0.99, and 1.0, respectively). No patients were reclassified from low to high volume disease or vice versa when switching from OSEM to BPL reconstruction. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT quantitative and volumetric parameters produced by BPL and OSEM reconstruction methods are strongly correlated. Differences are proportional and small for SUVmean, which is used as a predictive biomarker. Our study suggests that both reconstruction methods are acceptable without clinical impact on quantitative or volumetric findings. For longitudinal comparison, committing to the same reconstruction method would be preferred to ensure consistency.

Dual FDG/PSMA PET imaging to predict lesion-based progression of mCRPC during PSMA-RLT.

Candidates for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) frequently have "mismatch" lesions with pronounced 18-fluorodeoxyglucose ([18F]FDG) but attenuated PSMA ligand uptake on positron emission tomography (PET). However, no quantitative criteria yet exist to identify mismatch lesions and predict their response to RLT. To define such criteria, we retrospectively analyzed 267 randomly-selected glucometabolic mCRPC metastases from 22 patients. On baseline PET, we determined [18F]FDG and [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax), and calculated the [18F]FDG SUVmax/[68Ga]Ga-PSMA-11 SUVmax quotient (FPQ). From follow-up [18F]FDG PET after two lutetium-177-PSMA-617 RLT cycles, we evaluated the treatment response and categorized the lesions into three subgroups (partial remission, stable disease, progression) based on change in [18F]FDG SUVmax. Lastly, we compared the baseline PET variables in progressing versus non-progressing lesions. Variables differing significantly, and a score incorporating them, were assessed via receiver operator characteristic (ROC) curve analysis, regarding ability to predict lesional progression, with area under the curve (AUC) as metric. Cut-offs with optimal sensitivity and specificity were determined using the maximum value of Youden's index. Fifty-one of 267 lesions (19.1%) progressed, 102/267 (38.2%) manifested stable disease, and 114/267 (42.7%) partially responded after two RLT cycles. At baseline, median [68Ga]Ga-PSMA-11 SUVmax was significantly lower (p < 0.001), median FPQ significantly higher (p < 0.001), and median [18F]FDG SUVmax similar in progressing versus non-progressing lesions. [68Ga]Ga-PSMA-11 SUVmax and FPQ showed predictive power regarding progression (AUCs: 0.89, 0.90). An introduced clinical score combining both further improved predictive performance (AUC: 0.94). Optimal cut-offs to foretell progression were: [68Ga]Ga-PSMA-11 SUVmax < 11.09 (88.2% sensitivity, 81.9% specificity), FPQ ≥ 0.92 (90.2% sensitivity, 78.7% specificity), clinical score ≥ 6/9 points (88.2% sensitivity, 87.5% specificity). At baseline, a low [68 Ga]Ga-PSMA-11 SUVmax and a high FPQ predict early lesional progression under RLT; [18F]FDG SUVmax does not. A score combining [68 Ga]Ga-PSMA-11 SUVmax and FPQ predicts early lesional progression even more effectively and might therefore be useful to quantitatively identify mismatch lesions.

A PSMA PET/CT-based risk model for prediction of concordance between targeted biopsy and combined biopsy in detecting prostate cancer.

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.

A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience.

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.

Head-to-head comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT for the evaluation of tonsil cancer and lymph node metastases: a single-centre retrospective study.

BACKGROUND: This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer. METHOD: Twenty-one tonsil cancer patients who underwent [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed. RESULTS: In detecting primary lesions, the efficiency was higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [68 Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [18F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [18F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05). CONCLUSION: The availability of [68 Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.

Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BACKGROUND: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

Preclinical development of novel PD-L1 tracers and first-in-human study of [68Ga]Ga-NOTA-RW102 in patients with lung cancers.

BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.

68Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study.

INTRODUCTION: Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom 68Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of 68Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration. METHODS AND ANALYSIS: In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo 68Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by 68Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of 68Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067591.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

68Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients.

68Ga-labeled nanobody (68Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of 68Ga-NC-BCH for PET to determine its in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. Methods: Initially, we synthesized the probe 68Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. Results: 68Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,68Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. 68Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

De Novo Metastatic Prostate Cancer Presenting With Atypical Lower-Limb Skeletal Metastases Detected on 68 Ga-PSMA PET/CT.

ABSTRACT: Metastatic prostate cancer to the appendicular skeleton is rare. We present an 86-year-old man with undiagnosed prostate cancer presenting with unilateral foot pain. CT and MRI demonstrated a sclerotic midfoot suggestive of an infiltrative process. In view of an elevated PSA, metastatic disease was suspected, and bone scan confirmed osteoblastically active pelvic and lower-limb skeletal lesions. Subsequent prostate biopsy confirmed prostate adenocarcinoma. Staging 68 Ga-PSMA PET/CT demonstrated PSMA-avid intraprostatic malignancy with pelvic and right lower-limb skeletal metastases. This is an unusual case of de novo 68 Ga-PSMA-avid metastatic prostate cancer with atypical lower-limb skeletal metastases presenting with foot pain.

68 Ga-FAPI-04 PET/CT Imaging of Mesenteric Aggressive Fibromatosis.

ABSTRACT: Aggressive fibromatosis is a relatively rare disease. We describe 68 Ga-FAPI-04 PET/CT findings in a case of histologically proved mesenteric aggressive fibromatosis. 68 Ga-FAPI-04 PET/CT revealed a mass in the mesentery with increased FAPI activity. This case indicates that FAPI PET may be useful for evaluation of aggressive fibromatosis.

The Utility of Prostate-Specific Membrane Antigen-11 PET in Detection and Management of Central Nervous System Neoplasms.

ABSTRACT: We present a case series of 5 patients diagnosed with schwannoma and 1 patient diagnosed with astrocytoma who underwent PSMA PET imaging for tumor detection. We retrospectively analyzed the records of 4 male and 2 female patients (mean age, 53.2 ± 13.2) who underwent PSMA PET imaging between March and September 2023. PET interpretation showed increased Ga-PSMA-11 accumulation in all patients with a mean SUV max of 3.11 ± 1.8. This series underscores PSMA PET's potential for CNS neoplasm detection.