https://www.theragnostics.no/en/author/asta-juzeniene/ Asta Juzeniene Hugo Blox Builder (https://hugoblox.com)en-usWed, 21 May 2025 00:00:00 +0000 https://www.theragnostics.no/media/icon_hu14557955862192370321.png https://www.theragnostics.no/en/author/asta-juzeniene/ https://www.theragnostics.no/en/publications/h%C3%B8yvik-2025-therapeutic/ Wed, 21 May 2025 00:00:00 +0000 https://www.theragnostics.no/en/publications/h%C3%B8yvik-2025-therapeutic/ <hr> <p>Metastatic castration-resistant prostate cancer (mCRPC) frequently leads to bone and soft tissue metastases, leading to poor prognosis. The beta-emitting radioligand [¹⁷⁷Lu]Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA) and may be less efficient against micrometastatic disease. The alpha-emitting radioligand [²¹²Pb]Pb-AB001 could offer enhanced treatment by delivering high energy over a short range. This study compared the efficacy of [²¹²Pb]Pb-AB001 and [¹⁷⁷Lu]Lu-PSMA-617 in a mouse model of disseminated prostate cancer. Binding and internalisation of radioligands were evaluated in PC-3 PIP-luc cells. A mouse model was established by intracardiac injection of these cells. Treatments with 0.24‒1.0 MBq [²¹²Pb]Pb-AB001 or 22‒66 MBq [¹⁷⁷Lu]Lu-PSMA-617 were initiated 7 d post-cell inoculation. Metastatic burden was measured using bioluminescence imaging, and PSMA-targeted uptake was determined with [¹⁸F]F-PSMA-1007 µPET/µCT. Gamma-autoradiography evaluated [²¹²Pb]Pb-AB001 distribution, and bone metastases were identified by radiography. Both radioligands displayed comparable in vitro binding. In vivo studies revealed metastatic formation in clinically relevant organs. µPET/µCT demonstrated increased [¹⁸F]F-PSMA-1007 uptake in metastases, matching the bioluminescence imaging results. Focal [²¹²Pb]Pb-AB001 distribution in the metastatic xenograft indicated heterogeneously distributed micrometastases in the organs. A median survival up to 47 d was achieved with [²¹²Pb]Pb-AB001, compared to 25 d for controls and 27 d for [¹⁷⁷Lu]Lu-PSMA-617. An activity-dependent reduction in bone metastases was observed for [¹⁷⁷Lu]Lu-PSMA-617, while no bone lesions were detected in [²¹²Pb]Pb-AB001-treated mice. [²¹²Pb]Pb-AB001 showed significant efficacy against micrometastases and advantages over [¹⁷⁷Lu]Lu-PSMA-617 in preventing or treating early bone metastases for the investigated injected activities. This implies clinical potential for treating mCRPC, including patients at risk of early metastatic disease, but further studies including dosimetry and toxicity analyses are required with regards to activity levels.</p> https://www.theragnostics.no/en/publications/kvassheim-2023-imaging/ Mon, 21 Aug 2023 00:00:00 +0000 https://www.theragnostics.no/en/publications/kvassheim-2023-imaging/ <hr> <p>²¹²Pb is a promising radionuclide for targeted alpha therapy. Here, the feasibility of visualising the tumour uptake and biodistribution of ²¹²Pb-NG001 in mice with a clinical SPECT/CT scanner was investigated. A mouse phantom with ²¹²Pb was imaged with a clinical- and a preclinical SPECT/CT scanner. Different acquisition and reconstruction settings were investigated on the clinical system (Siemens Symbia Intevo Bold). Two athymic nude mice carrying PC-3 PIP prostate cancer tumours of 235-830 μl received 1.44 MBq of ²¹²Pb-NG001 and were imaged 2, 6, and 24 h post-injection on the clinical SPECT/CT with a Medium Energy collimator and a 40% energy window centred on 79 keV. All acquisition times were 30 min, except the mouse imaging 24 h post-injection which was 60 min. After the final imaging, the organs were harvested and measured on a gamma counter to give an indication of how much activity was present in organs of interest at the last imaging time point. Four volumes in the mouse phantom of ~ 300 μl with 246-303 kBq/ml of ²¹²Pb were distinguishable on images acquired with the clinical SPECT/CT with a high number of reconstruction updates. With the preclinical SPECT, the same volumes were easily distinguished with 49 kBq/ml of ²¹²Pb. Clinical SPECT/CT images of the mice revealed uptake in tumours and bladders 2 h after injection and in tumours containing down to approximately 15 kBq/ml at 6 and 24 h after injection. Although the preclinical scanner should be used preferentially in biodistribution studies in mice, the clinical SPECT/CT confirmed uptake in small volumes (e.g. ~ 300 μl volume with ~ 250 kBq/ml). Regardless of system, the resolution and sensitivity limits should be carefully determined, otherwise false negative or too low uptakes can be wrongly interpreted.</p>