Gozetotide 25microgram kit for radiopharmaceutical preparation

Steps have been taken by pharmaceutical companies to obtain marketing authorisation of PSMA ligands in the European Union. Since December 2022, Locametz® (PSMA-11, gozetotide) is licensed as kit for manual radiolabelling with gallium-68 and commercially available since mid-2023. The Summary of Product Characteristic (SmPC) describes manual radiolabelling with a maximum activity after radiolabelling of 1369 MBq. We aimed for radiolabelling with a higher activity to increase production efficiency, and thus, automated radiolabelling is strongly preferred over manual radiolabelling to reduce radiation exposure to personnel. The aim of this study was to develop and validate a method for automated radiolabelling of the Locametz® kit using ~ 2000 MBq of gallium-68 eluate for radiolabelling. Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit provided a product which complies to the Ph. Eur., had a shelf-life of 6 h at room temperature, and theoretically reduced radiation exposure 5.7 times. Radiolabelling with one and two generator(s) resulted in a radiochemical yield of 91–102% and 96–101% after preparation, respectively. The radiochemical purity ranged from 98.0 to 99.6% for radiolabelling with one generator and ranged from 98.4 to 99.3% for radiolabelling with two generators with similar stability. The activity of the final product was much higher when using two generators, 1961–2035 MBq compared to 740–1260 MBq, which leads to ~ 1.5 times more patient syringes available per preparation. Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit with higher gallium-68 activity than specified in the SmPC results in a product that is in compliance with the Ph. Eur. monograph and has a shelf-life of 6 h at room temperature. Radiolabelling with two generators proved possible and resulted in a product with similar quality but with much higher efficiency.

Abstract licence: CC BY 4.0

Prostate cancer (PCa) will affect approximately 12% of US men in their lifetime and remains the 2nd most common cause of cancer-specific death. However, there is a broad spectrum of severity of PCa; some require aggressive treatment and others can “watch-and-wait”. Distinction of clinically significant prostate cancer (csPCa) from indolent PCA with current imaging methods remains challenging. This study aims to evaluate dynamic prostate specific membrane antigen (PSMA) positron emission tomography (PET/CT) in the characterization of suspicious prostate lesions identified on multiparametric MRI (mpMRI). Prospective study of biopsy-naïve patients with at least one Prostate Imaging and Reporting Data System (PI-RADS) score 5 or one PI-RADS score 4 plus a prostate specific antigen (PSA) ≥ 10 ng/mL. Dynamic PET/CT was performed for 30 min after administration of 68Ga Gozetide. Time activity curves (TAC; kBq/cc) of suspicious prostate lesions were generated. TAC logarithmic slope was calculated for each GG at 5-, 10-, 15-, and 30 min. Apparent diffusion coefficient (ADC) at mpMRI for each lesion was tabulated. 19 PI-RADS v2.1 ≥ 4 and 6 secondary PI-RADS v2.1 ≥ 3 lesions in 19 patients were analyzed: 4 (16.0%) grade group (GG) 0 (benign), 3 (12.0%) GG 1, 6 (24.0%) GG 2, 6 (24.0%) GG 3, and 6 (24.0%) GG ≥ 4. Significant differences in slope values were observed between clinically insignificant disease (GG 0/1) and GG 2 or higher as early as 5 min post-injection (p < 0.05). At 30 min, GG 1 had the lowest mean slope (− 0.18 ± 0.57) and GG ≥ 4 exhibited the highest mean slope (2.35 ± 2.03). Slope value/ADC ratio further improved discrimination between different GGs. Dynamic 68 Ga Gozetotide time activity curves could distinguish GG0/1 from GG3 and GG4/5 PCa. The addition of mpMRI characteristics could further distinguish GG2 from GG4/5. GG2 could not be distinguished from GG3, probably due to small sample size. Clinical Implications. Dynamic 68 Ga Gozetotide PET/CT imaging may offer enhanced discrimination of MRI-visible prostate cancer lesions and assist in management decisions. Study registered with the FDA (IND 144,177) and clinicaltrials.gov (NCT04179968).

Abstract licence: CC BY-NC-ND 4.0

This phase II trial tests how well vorinostat works in treating patients with prostate-specific membrane antigen (PSMA)-low castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) (mCRPC). Prostate cancer that has not spread to other parts of the body (localized) is typically treated through surgery or radiotherapy, which for many men is curable. Despite definitive local therapy, cancer that has come back after a period of improvement (recurrent) disease develops in 27-53% of men. Often this is detected by measurement of prostate-specific antigen (PSA) without visible evidence of metastatic disease. Lutetium Lu 177 vipivotide tetraxetan (177Lu-prostate specific membrane antigen \[PSMA\]-617) is a new small molecule PSMA-targeted radioactive therapy that has been approved by the Food and Drug Administration for the treatment of adult patients with PSMA-positive mCRPC who have been treated with androgen receptor inhibitors and taxane-based chemotherapy. Vorinostat is used to treat various types of cancer that does not get better, gets worse, or comes back during or after treatment with other drugs. Vorinostat is a drug which inhibits the enzyme histone deacetylase and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and 177Lu-PSMA-617 may kill more tumor cells in in patients with PSMA-low mCRPC. Conditions: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8. Interventions: Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Fludeoxyglucose F-18, Gallium Ga 68 Gozetotide, Lutetium Lu 177 Vipivotide Tetraxetan, Positron Emission Tomography, Single Photon Emission Computed Tomography, Vorinostat.

Source: ClinicalTrials.gov (public domain)

In advanced metastatic castration resistant prostate cancer (mCRPC) progressing after chemotherapy and androgen receptor (AR)-targeted therapy 177Lu-PSMA-617 is an effective treatment. 177Lu-PSMA-617 RLT is administered with a fixed schedule: 6 treatment cycles, administered every 6 weeks. However, the optimum number of cycles of 177Lu-PSMA in patients who show good response remains unknown. Some patients may benefit from more than 6 cycles of therapy. Additionally, some patients experience a complete or almost complete response before the last cycle. It is unclear whether these patients benefit from the subsequent remaining treatment cycle(s). A treatment holiday period would spare these patients some exposure to the therapy agent and avoid potentially unnecessary toxicity when treatment efficacy is already maximal and additional treatment effect cannot be expected. This randomized phase 2 study compares a group of patients treated with LuPSMA on a flexible and extended dosing schedule including "treatment holiday" periods (investigational arm, up to 12 cycles, as described below) to a control group treated with a fixed dosing schedule of 6 treatments cycles maximum administered every 6 weeks. The flexible dosing schedule in the investigational arm will be based on single photon emission computed tomography (SPECT)/computed tomography (CT) response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on positron emission tomography/computed tomography (PET/CT) every 12 weeks. Single-time point SPECT/CT dosimetry protocol at every cycle will be performed and will allow to determine the number of cycles that subjects may receive under the study without exceeding the kidney dose threshold. Conditions: Prostate Carcinoma, Stage IVB Prostate Cancer American Joint Committee on Cancer (AJCC) v8. Interventions: Computed Tomography, Gallium Ga 68 Gozetotide, Lutetium Lu 177 Vipivotide Tetraxetan, Positron Emission Tomography, PSMA PET Scan, Questionnaire Administration, Single Photon Emission Computed Tomography.

Source: ClinicalTrials.gov (public domain)

This phase II trial tests how well re-treatment with 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic), that continues to grow or spread after the surgical removal of the testes or medical treatment to block androgen production (castration-resistant), and that has shown a favorable response to initial treatment with 177Lu-PSMA-617. 177Lu-PSMA-617 is a radioactive drug. It binds to a protein called prostate specific membrane antigen (PSMA), which is expressed by some types of prostate tumor cells. When 177Lu-PSMA-617 binds to PSMA-expressing tumor cells, it delivers radiation to the cells, which may kill them. Re-treatment with 177Lu-PSMA-617 in patients who had a favorable response to initial 177Lu-PSMA-617 treatment may improve survival outcomes and disease response in patients with metastatic castration-resistant prostate cancer. Conditions: Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8. Interventions: Biospecimen Collection, Computed Tomography, Gallium Ga 68 Gozetotide, Lutetium Lu 177 Vipivotide Tetraxetan, Positron Emission Tomography, Questionnaire Administration, Single Photon Emission Computed Tomography.

Source: ClinicalTrials.gov (public domain)

This phase II trial studies how to improve the usage of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen \[PSMA\]-617) for treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site), to other places in the body (metastatic) utilizing a treatment pause after 5 cycles of therapy versus standard continuous treatment for 6 cycles. Lutetium is a radioligand therapy (RLT). RLT uses a small molecule (in this case 177Lu-PSMA-617) that carries a radioactive component to destroy tumor cells. When lutetium is injected into the body, it attaches to the PSMA receptor found on tumor cells. After lutetium attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving 177Lu-PSMA-617 for 5 cycles versus 6 cycles may better treat patients with metastatic castrate resistant prostate cancer. Conditions: Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8. Interventions: Biospecimen Collection, Bone Scan, Clinical Observation, Computed Tomography, Gallium Ga 68 Gozetotide, Lutetium Lu 177 Vipivotide Tetraxetan, Positron Emission Tomography, Questionnaire Administration, Single Photon Emission Computed Tomography.

Source: ClinicalTrials.gov (public domain)