https://www.theragnostics.no/en/author/silje-selboe/ Silje Selboe Hugo Blox Builder (https://hugoblox.com)en-usThu, 01 May 2025 00:00:00 +0000 https://www.theragnostics.no/media/icon_hu14557955862192370321.png https://www.theragnostics.no/en/author/silje-selboe/ https://www.theragnostics.no/en/publications/berner-2025-first-in-human/ Thu, 01 May 2025 00:00:00 +0000 https://www.theragnostics.no/en/publications/berner-2025-first-in-human/ <hr> <p>AB001, a prostate-specific membrane antigen (PSMA)-targeted small molecule labeled with the in vivo-generating α-emitter ²¹²Pb, was investigated in a phase 0 trial in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary objective was to explore the feasibility of γ-camera imaging to assess biodistribution and uptake in metastatic lesions.</p> <p><strong>Methods:</strong> Three patients with progressive mCRPC and Eastern Cooperative Oncology Group performance status 1 were included, having prostate-specific antigen levels of 0.44, 0.75, and 15 µg/L. All had at least 3 PSMA-expressing metastatic lesions, with an SUV_max range of 10.1-77.4 on PSMA PET. Each patient received a microdose of 9.4 ± 0.3 MBq of AB001 intravenously. Planar γ-camera and SPECT/CT imaging was scheduled 1-3 h and 16-24 h after administration. Whole-body clearance was assessed with NaI probe measurements. Activity of ²¹²Pb in whole blood and plasma was measured to investigate clearance from blood and in vivo stability of the ligand. Safety, tolerability, and efficacy biomarkers (prostate-specific antigen, alkaline phosphatase) were followed for 28 d.</p> <p><strong>Results:</strong> AB001 uptake in the lesion with the highest PSMA expression, a retrocaval lymph node metastasis with a short-axis diameter of 11 mm, was visualized on SPECT. Uptake of AB001 was not clearly demonstrated for other metastatic lesions, possibly because of the lower PSMA expression of these metastases on PSMA PET, combined with the administered AB001 microdose and imaging system limitations. Kidney, urinary bladder with contents, and liver uptake of AB001 were clearly distinguishable from adjacent tissue, and the blood pool content was seen. Salivary glands were not visualized. Blood analyses indicated stability of AB001 after injection, and whole-body probe measurements demonstrated an effective half-life of 8 h. There were no complications related to injection of AB001 or adverse reactions during follow-up. As expected for a phase 0 study, there was no indication of therapeutic effects as assessed by prostate-specific antigen and alkaline phosphatase.</p> <p><strong>Conclusion:</strong> The ²¹²Pb-based radioligand AB001 was safely administered to mCRPC patients. γ-camera imaging of AB001 was feasible, even at a microdose, and demonstrated metastatic targeting, albeit for only 1 lesion. The promising biodistribution and clearance encourage further clinical investigation.</p> https://www.theragnostics.no/en/publications/gr%C3%B8nnings%C3%A6ter-2023-radiation/ Wed, 08 Feb 2023 00:00:00 +0000 https://www.theragnostics.no/en/publications/gr%C3%B8nnings%C3%A6ter-2023-radiation/ <hr> <p>Two ongoing phase I studies are investigating the use of radium-224 adsorbed to calcium carbonate micro particles (²²⁴Ra-CaCO₃-MP) to treat peritoneal metastasis originating from colorectal or ovarian cancer. The aim of this work was to study the level of radiation exposure from the patients to workers at the hospital, carers and members of the public. Six patients from the phase 1 trial in patients with colorectal cancer were included in this study. Two days after cytoreductive surgery, they were injected with 7 MBq of ²²⁴Ra-CaCO₃-MP. At approximately 3, 24 and 120 h after injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector, and whole body gamma camera imaging. The patient was modelled as a planar source to calculate dose rate as a function of distance. Scenarios varying in duration and distance from the patient were created to estimate the potential effective doses from external exposure. Urine and blood samples were collected at approximately 3, 6, 24, 48 and 120 h after injection of ²²⁴Ra-CaCO₃-MP, to estimate the activity concentration of ²²⁴Ra and ²¹²Pb. The patients&rsquo; median effective whole-body half-life of ²²⁴Ra-CaCO₃-MP ranged from 2.6 to 3.5 days, with a mean value of 3.0 days. In the scenarios with exposure at the hospital (first 8 days), sporadic patient contact resulted in a range of 3.9-6.8 μSv per patient, and daily contact resulted in 4.3-31.3 μSv depending on the scenario. After discharge from the hospital, at day 8, the highest effective dose was received by those with close daily contact; 18.7-83.0 μSv. The highest activity concentrations of ²²⁴Ra and ²¹²Pb in urine and blood were found within 6 h, with maximum values of 70 Bq/g for ²²⁴Ra and 628 Bq/g for ²¹²Pb. The number of patients treated with ²²⁴Ra-CaCO₃-MP that a single hospital worker - involved in extensive care - can receive per year, before effective doses of 6 mSv from external exposure is exceeded, is in the order of 200-400. Members of the public and family members are expected to receive well below 0.25 mSv, and therefore, no restrictions to reduce external exposure should be required.</p>