Intra-arterial PSMA injection using hepatic arterial infusion pump in intrahepatic cholangiocarcinoma: a proof-of-concept study.

Prostate-specific membrane antigen (PSMA) targeted tracers show increased uptake in several malignancies, indicating a potential for peptide radioligand therapy. Intra-arterial injection of radiotracers can increase the therapeutic window. This study aimed to evaluate the feasibility of intra-arterial injection of [68Ga]Ga-PSMA-11 for intrahepatic cholangiocarcinoma and compare tracer uptake after intrahepatic arterial injection and intravenous injection. Three patients with intrahepatic cholangiocarcinoma received [68Ga]Ga-PSMA-11 through a hepatic arterial infusion pump, followed by positron emission tomography/computed tomography (PET/CT). Two-three days later, patients underwent PET/CT after intravenous [68Ga]Ga-PSMA-11 injection. All tumours showed higher uptake on the intra-arterial scan compared with the intravenous scan: the intra-arterial / intravenous standardised uptake value normalised by lean body mass ratios were 1.40, 1.46, and 1.54. Local intra-arterial PSMA injection is possible in patients with intrahepatic cholangiocarcinoma. Local injection increases tumour-to-normal tissue ratios, increasing the therapeutic window for theranostic applications. RELEVANCE STATEMENT: Intra-arterial Prostate specific membrane antigen (PSMA) injection increases the therapeutic window for potential theranostic application in intrahepatic cholangiocarcinoma. KEY POINTS: Three patients with intrahepatic cholangiocarcinoma underwent PET/CT after intra-arterial and intravenous injection of [68Ga]Ga-PSMA-11. Intra-arterial injection showed higher uptake than intravenous injection. PSMA-targeted imaging could be valuable for a subset of intrahepatic cholangiocarcinoma patients.

Initial evaluation and external validation of 68Ga-PSMA-11 PET/CT in tubarial gland characterization.

INTRODUCTION: Radiotracer 68Ga-PSMA-11 used in PET/CT scans allows for identification and localization of gland tissue. It allows for their consideration in clinical scenarios and to design further and stronger research to answer pertinent questions regarding their function and implications. We aimed to externally validate first reported findings of location, size, and ligand uptake of the tubarial glands using 68Ga-PSMA-11 PET/CT. MATERIALS AND METHODS: A cross-sectional study was performed with 68Ga-PSMA-11 PET/CT studies of patients with prostate cancer confirmed diagnosis from the database of the Radiology Department from 2018 to 2022. The maximum cephalocaudal length (CCL) in the tubarial glands and the Maximum Standardized Uptake Value (SUVmax) of major glands were recorded. RESULTS: A total of 202 patients were included (mean age 67.43 ± 8.5). The mean CCL of the tubarial glands was 37.38 ± 9.84 and a SUVmax of 6.56 ± 2.14. The rest of the glands were as follows: parotid 15.12 ± 4.43, submandibular 16.82 ± 5.43 and sublingual 5.84 ± 3.24. No differences were found between laterality. A weak correlation between age and SUVmax of tubarial glands was identified. Tubarial glands had a similar 68Ga-PSMA-11 uptake to that of sublingual glands. CONCLUSION: This study corroborates the existence of a conglomerate of glands in the nasopharynx roof, near the posterolateral pharyngeal recess. It serves as validation in a different population with similar results in previous research. Without 68GA-PSMA-11 PET/CT the abundance, configuration and potential clinical relevance of these glands would probably not have been identified. Radiotracer uptake was similar amongst the major salivary glands, with a more similar uptake to that shown by the sublingual gland.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

PURPOSE: Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). METHODS: Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. RESULTS: Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. CONCLUSION: 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer.

OBJECTIVE: Lutetium-177 (Lu177) prostate-specific membrane antigen (Lu177 PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (CRPC). The purpose of the study was to determine the molecular volumetric Gallium-68 (Ga68) PSMA PET/CT parameters that can predict patients who will respond to treatment. METHODS: These single-center retrospective data were obtained from metastatic CRPC patients receiving intravenous 6.0-8.5 GBq Lu177 PSMA treatment every 6-8 weeks for a maximum of 3-8 cycles, with baseline Ga68 PSMA PET/CT scan, clinical data, and information on treatment responses. All lesions were divided into two groups according to the increase and decrease in PSMA expression levels of 600 bone lesions and 85 lymph nodes that were compatible with metastasis of 23 patients after the treatment. The primary endpoint of our study was the evaluation of the relation between the baseline SUVmax, PSMA TV, TL PSMA values, and the treatment response of the two groups. The threshold values were determined for the parameters that had significant relations. In the present study, the prostate-specific antigen (PSA) response and treatment-induced toxicities were also evaluated as the secondary endpoint. RESULTS: It was found that SUVmax, PSMA TV, and TL PSMA values in bone metastases showed significant differences between the groups with decreased and increased PSMA expression levels after the treatment. The AUC value for SUVmax was significant (AUC = 0.677; p < 0.001). The cutoff value was > 10.50 (sensitivity = 91.8%, Specificity = 41.5%) for SUVmax, > 1.50 cm3 (sensitivity = 49.1%, specificity = 70%) for PSMA TV and > 8.50 g (sensitivity = %60.9, specificity = %72.2) for TL PSMA. The median SUVmax value before the treatment in all metastatic lymph nodes was found to be 7.1 (5.4-12.4), and the median SUVmax after the treatment was 2.5 (1.6-12.1) (p < 0.001). CONCLUSION: It was shown in the present study that Lu177 PSMA treatment response may be higher in CRPC patients with metastatic bone lesion with high baseline PSMA expression level, and better treatment response may be achieved in patients with lymph node metastases than in bone metastases.

Necessity of Pelvic Lymph Node Irradiation in Patients with Recurrent Prostate Cancer after Radical Prostatectomy in the PSMA PET/CT Era: A Narrative Review.

The main prostate cancer (PCa) treatments include surgery or radiotherapy (with or without ADT). However, none of the suggested treatments eliminates the risk of lymph node metastases. Conventional imaging methods, including MRI and CT scanning, are not sensitive enough for the diagnosis of lymph node metastases; however, the novel imaging method, PSMA PET/CT scanning, has provided valuable information about the pelvic LN involvement in patients with recurrent PCa (RPCa) after radical prostatectomy. The high sensitivity and negative predictive value enable accurate N staging in PCa patients. In this narrative review, we summarize the evidence on the treatment and extent of radiation in prostate-only or whole-pelvis radiation in patients with positive and negative LN involvement on PSMA PET/CT scans.