Ziel/Aim Fibroblast activation protein (FAP) is involved in cancerogenesis by promoting tumor cell migration, invasion and angiogenesis. Moreover, due to its overexpression in malignant tissue on activated fibroblasts and less abundance in normal healthy tissue, FAP ligands may consist a tool for in vivo tumor imaging and potential therapeutic applications of a variety of tumors. Herewith, we evaluate the in vitro and in vivo performance of three FAP radioligands to serve as diagnostic tools of FAP-positive tumors.

Ziel/Aim Cancer-associated fibroblasts (CAFs) in tumor microenvironment have been implicated to possess a strong tumor-modulating effect in various solid tumors [1]. Fibroblast activation protein (FAP) overexpressed on the CAFs surface is a promising target for cancer diagnosis and therapy due to its non-expression in normal fibroblasts and benign epithelial tumors [2]. Herein, we investigated the 68Ga-labeled FAP inhibitor ([68Ga]Ga-DOTA.SA.FAPi) performance, including radiosynthesis, lipophilicity, protein binding, saturation/internalization studies, and stability while the in vivo evaluation in tumor-bearing mice is underway.

Ziel/Aim The good efficacy of the targeted radionuclide-based therapy using 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer has been demonstrated in several clinical studies. However, the treatment effect is still suboptimal for a significant fraction of patients and a substantial individual variance in lesion radiation dose is well known. Physiologically-based pharmaco-kinetic (PBPK) models have been established to assist the personalization of RLT. However, an in-depth insight of the interaction with tumor microenvironment is not provided. We propose an in silico approach to investigate the distribution of the radionuclide inside the tumor microenvironment through a PBPK-based convective-diffusion-reaction (CDR) model.

The good efficacy of radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has been recently demonstrated in several clinical studies. However, the treatment effect of 177Lu-PSMA-ligands is still suboptimal for a significant fraction of patients. In contrast to external beam radiotherapy, the radiation dose distribution itself is strongly influenced by the heterogeneous tumour microenvironment. Although microdosimetry is critical for RLT treatment outcome, it is difficult to clinically or experimentally establish the quantitative relation. We propose an in silico approach to quantitatively investigate the microdosimetry and its influence on treatment outcome for PSMA-directed RLT of two different radioisotopes 177Lu and 225 Ac. The ultimate goal is optimize the combined 177 Lu and 225 Ac-PSMA therapy and maximize the anti-tumour effect, while minimizing irradiation of off-target tissues.Clinical relevance- With the proposed hybrid model we show that 177Lu-PSMA-ligands treatment assures a more homogeneously distributed dose and a lower dependency of the treatment outcome on the domain vascularisation. On the other hand, the 225Ac-PSMA-ligands treatment shows a much stronger efficacy in killing tumor cells with an equivalent mean dose distribution even in an hypoxic environment.

Ziel/Aim The present study aims at investigating the influence of the versatile bifunctional chelator AAZTA5 on a Gastrin Releasing Peptide receptor (GRPr)-based antagonist and assessing its potential in serving as theranostic compound for GRPr-positive tumors.

Ziel/Aim The aim of this study was to investigate an optimised imaging protocol combining late additional imaging with additional hydration and forced diuresis.

Ziel/Aim The urinary excretion of PSMA-ligands with resultant high bladder activity can obscure locally relapsing prostate cancer (PC) lesions in Positron-Emission-Tomography/Computed Tomography (PET/CT). While a number of studies report the role of forced diuresis in PSMA-PET/CT, its influence on local recurrence detectability has not been extensively studied, which this present study aims to address.