Charting the Course of Targeted α Therapy With First-in-Human, Postadministration Image-Guided Dosimetry and Response Assessment of 212 Pb-VMT-α-NET in Metastatic Neuroendocrine Tumors.

ABSTRACT: 212 Pb emerges as a compelling in vivo α-particle generator for targeted α therapy due to its favorable half-life ( t1/2 = 10.6 hours) aligning with the biological half-lives of small peptides and its potent α-particle emissions within the decay series. However, one of the challenges with 212 Pb is to perform appropriate image-guided dosimetry. To date, all the data have been extrapolated from its imaging analog, 203 Pb. We present the first-in-human posttherapy image-guided dosimetric estimates of a single cycle of 212 Pb VMT-α-peptide, administered in a 41-year-old woman with an advanced grade 2 NET. The patient also demonstrated partial response on treatment.

Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

BACKGROUND: Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION: 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING: None.

18F-FDG PET/CT in Bilateral Breasts Metastasis From Ovarian Carcinoma.

ABSTRACT: Ovarian carcinomas generally metastasize within the peritoneal cavity due to exfoliation of malignant cells from primary tumor. Metastasis to the breasts is an unusual event and may mimic primary neoplastic disease. Usually, breast metastasis presents as a single isolated, well-circumscribed soft tissue lesion, and serous papillary carcinoma is the most common type of ovarian tumor that can metastasize to the breast. Concurrent bilateral breast metastasis is rare event. We present a follow-up case of metastatic carcinoma ovary, demonstrating FDG-avid soft tissue density masses in the bilateral breast parenchyma along with bilateral axillary lymphadenopathy, biopsy of which revealed metastatic deposits from carcinoma ovary.

Upfront Use of 177Lu-Labeled PSMA Radioligand Therapy and Treatment Response Assessment in Treatment-Naive Prostate Cancer.

ABSTRACT: Prostatic malignancy is the most common type of nonskin cancer and associated with significant morbidity and mortality. Early androgen deprivation therapy (ADT) is the treatment of choice in metastatic prostate cancer, whereas ADT delays progression of disease, but it is associated with significant adverse effects and frequently impairs the quality of life. Therefore, there is growing interest in treatments to postpone ADT while achieving a good progression-free survival. We present a case of oligometastatic prostate cancer, who was treated upfront with 177Lu-labeled PSMA radioligand therapy and demonstrated excellent response to a single dose of 177Lu-PSMA-617.

Prospects of medium specific activity (177) Lu in targeted therapy of prostate cancer using (177) Lu-labeled PSMA inhibitor.

Targeted radionuclide therapy using (177) Lu-labeled peptidomimetic inhibitor of prostate specific membrane antigen (PSMA) viz. PSMA-617 is emerging as one the most effective strategies for management of metastatic prostate cancer, which is one of the leading causes of cancer related death. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of therapeutic dose of (177) Lu-PSMA-617 at hospital radiopharmacy using moderate specific activity (177) Lu available at an affordable cost. Extensive radiochemical studies were performed to optimize the required [PSMA-617] / [Lu] ratio and other parameters to formulate 7.4 GBq dose of (177) Lu-PSMA-617. Based on these, 7.4 GBq therapeutic dose of (177) Lu-PSMA-617 was formulated by incubating 160 µg of PSMA-617 with indigenously produced (177) LuCl3 (555 GBq/µg specific activity of (177) Lu) at 90 °C for 30 min. The radiochemical purity of the formulation was 98.3 ± 0.6% (n = 7) which was retained to the extent of >95% after 7 d in normal saline at room temperature and >96% after 2 d in human serum at 37 °C. Preliminary clinical studies showed specific targeting of the agent in the lesion sites and similar physiological distribution as in diagnostic (68) Ga-PSMA-11 PET scans performed earlier. The developed optimized protocol for formulating therapeutic dose of (177) Lu-PSMA-617 could be useful for large number of nuclear medicine therapy clinics across the world having access to moderate specific activity (177) Lu at an affordable cost.

Comparing SUV values of images at PET-CT console and the RT planning console using identical dataset of a study phantom.

PURPOSE: The use of positron emission tomography (PET) for radiotherapy planning purposes has become increasingly important in the last few years.In the current study, we compared the SUV values of images at the PET CT console to the SUV values obtained at the RT planning workstation. MATERIALS AND METHODS: The PET-CT cylindrical body phantom was filled with a uniform 18F solution of 5.3. ± 0.27 kBq/mL radioactivity concentration. PET-CT scans were performed on a16 slice Time of Flight system. On a single day, the three consecutive scans were done at three time points 15 minutes apart to generate time points image data sets titled T1, T2, and T3. SUV calculations were performed by drawing region of interest. (ROI) encompassing the entire hot spot on each slice on the PET-CT console and the iPlan workstation. Minimum SUV, Maximum SUV and the Mean SUV were recorded. Statistical analysis was done using the SPSS software. (SPSS Inc.) (Version 18). RESULTS: The absolute difference in average max SUV values i.e. Max (PET-CT) - Max (iPlan) for the time points T1, T2 and T3 were -0.168 (SD 0.175), -0.172 (SD 0.172) and -0.178 (SD 0.169). The difference in the minimum SUV values were -0.513 (SD 0.428), -0.311 (SD 0.358) and -0.303 (SD 0.322), respectively. Finally, the difference in the mean SUV values were -0.107 (SD 0.040), -0.096 (SD 0.067) and -0.072 (SD 0.044), respectively. CONCLUSIONS: Our study found out that the average difference in the two systems for maximum SUV values was < 0.2 absolute units.Our study suggests good reproducibility of SUV between the two systems. The relevance of these findings would be of seminal importance in current and future SUV-based PET-CT-based contouring in treatment planning systems.

Role of ¹8F-FDG PET CT as an independent prognostic indicator in patients with hepatocellular carcinoma.

OBJECTIVES: The aim of the study was to evaluate the role of F-fluorodeoxyglucose PET computed tomography (F-FDG PET CT) as an independent prognostic indicator in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PET contrast-enhanced CT scans of 100 consecutive patients with HCC were reviewed retrospectively. Patients were asked to fast for 6 h before the study and blood glucose levels were monitored and ensured to be less than 200 mg/dl before injection of F-FDG. After administering the F-FDG injection (370-550 MBq) patients were instructed to rest comfortably for 45-60 min. All images were acquired using a dedicated GE Discovery PET/CT scanner. The PET CT scans of all the patients were reported separately by two nuclear medicine physicians. A stage-wise analysis of the compiled data was carried out. Lesions that showed standardized uptake values greater than background activity (activity in adjacent normal liver tissue) were defined as having increased F-FDG uptake. Pearson's χ -test or the Kruskal-Wallis test was used to assess statistical significance. A P value less than 0.05 was taken as significant. RESULTS: In this retrospective study of 100 HCC patients, a radiologically higher-stage disease was found more commonly in patients with F-FDG-avid primary tumors (P<0.001), whereas a lower-stage disease was found in patients with non-F-FDG-avid primary tumors. The non-F-FDG-avid tumors also showed lower incidence of metastatic disease and portal vein thrombosis (P<0.001). The histopathological findings of the patients who underwent liver transplantation demonstrated that a higher-grade tumor was more common in the F-FDG-avid tumor group than in the non-F-FDG-avid tumor group (P<0.05). CONCLUSION: An F-FDG PET CT scan can be used not only for staging but also as a tool for preoperative prediction of cellular differentiation in patients with HCC. The F-FDG uptake seen on a PET scan can serve as a molecular signature for management decisions and can be used as an independent and significant prognostic factor in patients with HCC.