Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study.

PURPOSE: Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [225Ac]Ac-PSMA-617, a targeted alpha therapy (TAT) that administers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. In this study, we report the long-term survival outcomes of this novel therapy in a series of patients with mCRPC who have exhausted all standard treatment options. METHODS: The study enrolled patients with mCRPC who had shown resistance to standard lines of therapies, including next-generation anti-androgen therapies and taxane-based chemotherapies. These eligible patients received treatment with [225Ac]Ac-PSMA-617 at 100-150 kBq/kg doses administered every 8 weeks. The primary objective of the study was to assess overall survival (OS), while secondary objectives included evaluating radiological progression-free survival (rPFS), monitoring serum prostate-specific antigen (PSA) levels as a measure of biochemical response, and assessing adverse events using the CTCAE v5.0 grading system. RESULTS: Among the 63 initially enrolled patients, a total of 56 patients who had completed at least two cycles of [225Ac]Ac-PSMA-617 were included in this study. The mean age was 67 years (range, 39-87) and patients received a total of 204 cycles of [225Ac]Ac-PSMA-617 TAT. 91% of patients exhibited any PSA decline, with 67.8% experiencing a decline of 50% or more. The median follow-up was of 22 months (range: 6-59 months). Imaging-based disease progression was observed in 68% of patients, and 66% of patients succumbed to the disease. The median OS was 15 months (95% CI: 10-19). In univariate analysis, factors such as lack of >50% PSA decline (P=0.031), Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher (P=0.048), and radiological progression (rPD) (P<0.001) were found to be predictors of poor OS. However, in multivariate analysis, only rPD emerged as an independent prognostic factor with a hazard ratio (HR) of 8.264 (95% CI: 1.429-16.497, P=0.004). The estimated median rPFS was 9 months (95% CI: 7-15). Moreover, patients who demonstrated any PSA decline had a median rPFS of 10 months compared to only 3 months in patients without any PSA decline (multivariate HR: 6.749; 95% CI: 1.949-23.370; P=0.002). Fatigue was one of the most common treatment-emergent adverse events, with grades 1/2 occurring in 70% of patients and grades 3 or higher in 3.5% of patients. This fatigue was transient and resolved before the next treatment cycle. Additionally, approximately one-third of patients experienced xerostomia (grades 1/2: 32.1%). CONCLUSION: [225Ac]Ac-PSMA-617 targeted alpha therapy, was found to be well-tolerated with acceptable adverse events and effective in the treatment of patients with end-stage mCRPC.

Complete Response to 177 Lu-DOTATATE PRRT in a 9-Year-Old Child With Metastatic Carotid Body Paraganglioma.

ABSTRACT: We present a case involving a 9-year-old boy diagnosed with metastatic carotid body paraganglioma. The metastases were detected in cervical lymph nodes and lungs using 68 Ga-DOTANOC PET/CT imaging. The patient received peptide receptor radionuclide therapy with 177 Lu-DOTATATE. Following 3 treatment cycles, a significant improvement was observed in the metastatic lesions. After 4 cycles, the patient achieved a complete response, with a cumulative administered activity of 16.65 GBq during the therapy. This case underscores the effectiveness of using 177 Lu-DOTATATE in managing metastatic carotid body paraganglioma, offering promising results in terms of tumor regression and overall therapeutic response.

Discordant Molecular Imaging Findings with 2-[18F]FDG and [68Ga]Ga-PSMA PET/CT in a Patient with Both Bladder and Prostate Cancer.

The prevalence of double primary prostate and bladder cancer is not uncommon. Though both share a common pathway of malignant transformation, they bear to differ in the case of 2-[18F]FDG PET/CT and [68Ga]Ga-PSMA uptake. We present a case of double primary cancer involving the bladder and prostate, where the prostatic primary showed intense [68Ga]Ga-PSMA uptake with non-avid skeletal and pulmonary metastases, which showed intense 2-[18F]FDG uptake, thus showing discordance due to different clonal origins.

[177Lu]Lu-DOTAGA.Glu.(FAPi)2 Radionuclide Therapy: a New Treatment Option for Patients with Glioblastoma Multiforme.

In this case report, we present the clinical management of a 52-year-old female patient with a recurrent right temporo-parietal glioblastoma multiforme (GBM). The patient presented with symptoms of headache and loss of balance and recurrence on magnetic resonance imaging (MRI). To evaluate the fibroblast activation protein inhibitor (FAPi) expression in the recurrent lesion, an exploratory [68 Ga]Ga-DOTA.SA.FAPi PET/CT scan was performed. The imaging results revealed FAPi expression in the lesion located in the right temporo-parietal region. Based on the findings of FAPi expression, the patient underwent [177Lu]Lu-DOTAGA.Glu.(FAPi)2 treatment. After completing two cycles of [177Lu]Lu-DOTAGA.Glu.(FAPi)2 therapy, a follow-up [68 Ga]Ga-DOTA.SA.FAPi PET/CT scan was conducted. The post-treatment imaging showed a significant reduction in FAPi uptake and regression in the size of the lesion, as well as a decrease in perilesional edema, as observed on the MRI. Furthermore, the patient experienced an improvement in symptoms and performance status. These results suggest that [68 Ga]Ga-DOTA.SA.FAPi monomer imaging and [177Lu]Lu-DOTAGA.Glu.(FAPi)2 dimer therapeutics hold promise for patients with recurrent GBM when other standard-line therapeutic options have been exhausted. This case highlights the potential of using FAPi-based theranostics in the management of recurrent GBM, providing a potential avenue for personalized treatment in patients who have limited treatment options available.

Impact of forced diuresis at two different time points on pelvic imaging in prostatic carcinoma with 68 Ga-PSMA PET/CT.

OBJECTIVE: We compared diagnostic quality of 68 Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. MATERIAL AND METHODS: A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68 Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68 Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. RESULTS: Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points ( P  > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P  < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P  = 0.002). CONCLUSION: The simultaneous furosemide and 68 Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.

Head-to-Head Comparison between [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT Imaging in Patients with Breast Cancer.

This study aimed to compare the diagnostic performance of [68Ga]Ga-DOTA.SA.FAPi with that of [18F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer. [18F]F-FDG and [68Ga]Ga-DOTA.SA.FAPi PET/CT scans of histologically proven breast cancer patients were compared according to patient-based and lesion-based analysis. Forty-seven patients with a mean age of 44.8 ± 9.9 years (range: 31-66 years) were evaluated. A total of 85% of patients had invasive ductal carcinoma, and 15% had invasive lobular carcinoma. The tracer uptake [SULpeak, SULavg, and the median tumor-to-background ratio (TBR)] was significantly higher in [68Ga]Ga-DOTA.SA.FAPi than with [18F]F-FDG PET/CT for lymph nodes, pleural metastases, and liver lesions (p < 0.05). However, for brain metastasis, only the median TBR was significantly higher (p < 0.05) compared to [18F]F-FDG. In patient-based analysis the sensitivity of [68Ga]Ga-DOTA.SA.FAPi PET/CT was higher, but not significant than that of [18F]F-FDG PET/CT in the detection of both primary tumors and metastatic lesions. According to lesion-based analysis, on diagnostic CT, 47 patients had 44 primary tumors, 248 lymph nodes, 15 pleural, 88 liver, and 42 brain metastases. [68Ga]Ga-DOTA.SA.FAPi scan identified more abnormal lesions than [18F]F-FDG in all the primary and metastatic sites with a maximum marked difference in the primary site [88.6% vs. 81.8%; p-0.001], lymph nodes [89.1% vs. 83.8%; p-0.0001], pleural metastases [93.3% vs. 73%; p-0.096] and brain metastasis [100% vs. 59.5%; p-0.0001]. [68Ga]Ga-DOTA.SA.FAPi PET/CT was superior to [18F]F-FDG PET/CT in the imaging of breast cancers.

Head-to-Head Comparison of [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer.

Background: A theranostic probe for accurate staging and treatment is crucial for the management of medullary thyroid cancers (MTCs). The abundance of stroma in most of thyroid cancers, including MTC, opens new avenues for selecting cancer-associated fibroblasts (CAFs) as new molecular imaging and therapeutic targets. [68Ga]Ga-labeled fibroblast activation protein inhibitor (FAPi) molecules have gained importance as alternative molecular imaging agents in the imaging of thyroid cancers. The purpose of this study was to compare the detection efficiency of primary and metastatic lesions of MTCs between [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC positron emission tomography (PET) radiotracers. Materials and Methods: In this retrospective study, [68Ga]Ga-DOTANOC and [68Ga]Ga-DOTA.SA.FAPi PET/CT (computed tomography) images were compared using patient-based and lesion-based analysis in patients with MTC for follow-up assessment. The quantitative assessment included comparing standardized uptake values corrected for lean body mass (SULpeak) and tumor-to-background ratios (TBR). The findings on both scans were validated with the morphological findings of the diagnostic CT. Results: Twenty-seven patients (21 males and 6 females) with a mean age of 42.4 ± 13.2 years (range 14-66 years) were included in the study. [68Ga]Ga-DOTA.SA.FAPi had similar sensitivities as that of [68Ga]Ga-DOTANOC PET/CT for detecting primary tumors (100% [18 of 18] vs. 94.4% [17 of 18], p = 0.979) involved lymph nodes (98.3% [118 of 120] vs. 95% [114 of 120], p = 0.288), and brain metastases (100%). [68Ga]Ga-DOTA.SA.FAPi demonstrated significantly higher sensitivities than [68Ga]Ga-DOTANOC PET/CT for detecting lung nodules (93.5% [87 of 93] vs. 68.9% [64 of 93], p < 0.0001), liver (100% [105 of 105] vs. 46.4% [49 of 105], p < 0.0001), bone (92.4% [110 of 119] vs. 76.5% [91 of 119], p = 0.001), and pleural metastases 98.2% versus 0%. Higher uptake values and TBR values were reported with [68Ga]Ga-DOTA.SA.FAPi compared with that of [68Ga]Ga-DOTANOC. Conclusion: [68Ga]Ga-DOTA.SA.FAPi outperformed [68Ga]Ga-DOTANOC PET/CT in the detection of distant metastases with both patient-based and lesion-based analysis in MTCs.

An Appraisal and Update of Fluorodeoxyglucose and Non-Fluorodeoxyglucose-PET Tracers in Thyroid and Non-Thyroid Endocrine Neoplasms.

Endocrine neoplasms and malignancies are a diverse group of tumors with varied clinical, histopathologic, and functional features. These tumors vary from sporadic to hereditary, isolated entities to multiple neoplastic syndromes, functioning and non functioning tumors, unifocal locally invasive, and advanced to multifocal tumors with disseminated distant metastases. The presence of various specific biomarkers and specific receptor targets serves as valuable tools for diagnosis, prognosis, and management. PET-CT with FDG and a multitude of novel and specific radiotracers towards specific therapeutic targets mandates personalization of their use, so as to ensure maximum clinical benefit in the management of these neoplasms.

Fibroblast Activation Protein Inhibitor Theranostics.

The evolution of the fibroblast activation protein inhibitor molecules over the past decade has brought into the forefront a novel theranostic agent that has the potential of matching the workhorse of PET/computed tomography, [fluorine-18] fluoro-2-deoxy-d-glucose (18F-FDG). It is hoped that in the next decade it can act as a complementary tracer to 18F-FDG, in providing phenotypic and biomarker information and also in directing fibroblast activation protein-targeted therapies.

Spectrum of 18F-FDG Uptake in Bilateral Lung Parenchymal Diseases on PET/CT.

Bilateral lung parenchymal involvement is seen in infective as well as noninfective conditions, appearing as focal or diffuse lung disease. PET/CT with FDG helps in characterization (increased glucose utilization is seen by both inflammatory and neoplastic cells). In this article, we describe the spectrum of patterns of FDG uptake and associated CT changes involving bilateral lung parenchyma. Benign conditions described are aspiration pneumonia; pulmonary toxicity by bleomycin; infections, namely, sarcoidosis, miliary pulmonary tuberculosis, and pulmonary nocardiosis; and inflammatory conditions such as pulmonary Langerhans cell histiocytosis and pulmonary alveolar proteinosis. Neoplastic conditions described are bilateral pulmonary metastases and lymphangitic carcinomatosis.

Is there a utility of adding skeletal imaging to 68-Ga-prostate-specific membrane antigen-PET/computed tomography in initial staging of patients with high-risk prostate cancer?

PURPOSE: Both bone-scan and cross-sectional imaging are indicated in the staging of high-risk prostate cancer (PCa). However, 68Ga-prostate-specific membrane antigen (PSMA)-PET/computed tomography (CT) has proven to be an excellent tracer for detection of skeletal metastases. The aim of this study was to assess if adding skeletal imaging (with 18F-Fluoride-PET/CT) to 68-Ga-PSMA-PET/CT had any impact on high-risk PCa staging. METHOD: Fifty treatment-naive, histopathologically proven, high-risk (European Association of Urology) PCa patients underwent both 68-Ga-PSMA-PET/CT and 18F-Fluoride-PET/CT for staging. RESULTS: Fluoride-PET/CT detected significantly a higher number of skeletal metastases/patient than PSMA-PET/CT (median 4.5/patient vs 3.0; Wilcoxan-signed-rank-test, P = 0.060) and there was a significantly higher proportion of only Fluoride-avid than only PSMA-avid lesions (McNemar-test P < 0.001). No significant advantage was seen in patient-wise metrics. Most lesions missed by PSMA-PET/CT were in flat bones (25/33). serum prostate specific antigen (S.PSA) showed positive correlation with both, the number of lesions [r(PSMA)-0.555 (P = 0.006) and r(Fluoride)-0.622 (P = 0.001)] as well as tumor to background ratio (TBR) [[r-0.706 (P < 0.001) and 0.516 (P = 0.010)]. Median TBR was significantly higher in PSMA-PET/CT (22.77 vs 16.30; P < 0.001). All three patients with only Fluoride-avid lesions (also not identified in bone-scan) showed biochemical response with additional therapy. CONCLUSION: Though, Fluoride-PET/CT detected a higher absolute number of lesions than PSMA-PET/CT, no significant advantage was seen in patient-wise metrics. Fluoride-PET/CT added second-line management in only 3/50 patients, which could have been reduced to 1/50, with more sensitive evaluation of flat bones in PSMA-PET-CT. Therefore, additional skeletal imaging is not needed with 68-Ga-PSMA-PET/CT in initial staging of high-risk PCa.

Unilateral Brown Fat Suppression on FDG PET/CT-detecting Sympathetic Denervation.

We present here a case of primitive neuroectodermal tumor (PNET) who initially presented with involvement of the right 3rd rib and underwent neoadjuvant chemotherapy, rib excision, and adjuvant chemoradiotherapy and later underwent posterolateral thoracotomy, pleural nodule excision, and the right 11th rib metastatic lesion excision. Follow-up 18F-FDG PET/CT/computed tomography revealed unilateral brown fat suppression in the form of decreased metabolic uptake in the ipsilateral cervical, axillary, and paravertebral brown fat as compared to metabolically active contralateral brown fat, likely due to paravertebral sympathetic chain damage.