Signaling Network Response to α-Particle-Targeted Therapy with the Ac-Labeled Minigastrin Analog Ac-PP-F11N Reveals the Radiosensitizing Potential of Histone Deacetylase Inhibitors.

α-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted α-particle therapy (TAT). Identification of the radiation-activated mechanisms that drive cancer cell survival provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT.

Therapeutic Response of CCKBR-Positive Tumors to Combinatory Treatment with Everolimus and the Radiolabeled Minigastrin Analogue [Lu]Lu-PP-F11N.

The inhibition of the mammalian target of rapamycin complex 1 (mTORC1) by everolimus (RAD001) was recently shown to enhance the tumor uptake of radiolabeled minigastrin. In this paper, we investigate if this finding can improve the in vivo therapeutic response to [Lu]Lu-PP-F11N treatment. The N-terminal DOTA-conjugated gastrin analogue PP-F11N (DOTA-(DGlu)-Ala-Tyr-Gly-Trp-Nle-Asp-Phe) was used to evaluate treatment efficacy in the human A431/CCKBR xenograft nude mouse model in combination with RAD001.

Evaluation of Actinium-225 Labeled Minigastrin Analogue [Ac]Ac-DOTA-PP-F11N for Targeted Alpha Particle Therapy.

The overexpression of cholecystokinin B receptor (CCKBR) in human cancers led to the development of radiolabeled minigastrin analogues for targeted radionuclide therapy, which aims to deliver cytotoxic radiation specifically to cancer cells. Alpha emitters (e.g.

Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours.

Purpose: Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available beta-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using (111)In-labelled derivatives.

Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours.

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET.

Improved tumour detection by gastrin receptor scintigraphy in patients with metastasised medullary thyroid carcinoma.

Purpose: Radiopeptide imaging is a valuable imaging method in the management of patients with neuroendocrine tumours (NET). To determine the clinical performance of gastrin receptor scintigraphy (GRS), it was compared with somatostatin receptor scintigraphy (SRS), computed tomography (CT) and (18)F-FDG positron emission tomography (PET) in patients with metastasised/recurrent medullary thyroid carcinoma (MTC).

Methods: Twenty-seven consecutive patients underwent imaging with GRS, SRS (19 patients), CT and PET (26 patients).

Imaging lung tumors with peptide-based radioligands.

The somatostatin analogue octreotide was the first radiopeptide to be used for the scintigraphic diagnosis of tumors. Somatostatin receptor scintigraphy (SRS) has proven its value, especially in the detection of gut neuroendocrine tumors. In some tumor types, it is considered the diagnostic gold standard.

Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical management of patients with gastrointestinal neuroendocrine tumors: an analysis in 188 patients.

Aim: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT.

Patients And Methods: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient.

Negative correlation between therapeutic success in radioiodine therapy and TcTUs: are TcTUs-adapted dose concepts the only possible answer?

Calculation of iodine-131 activities for radioiodine treatment (RIT) in patients with disseminated thyroid autonomy may be difficult because of uncertainties in the determination of the autonomous volume (vol(aut)). The algorithm established by Emrich is used for calculation of the vol(aut) based on the TcTUs (technetium thyroid uptake under TSH suppression) (vol(aut)= 5xTcTUs+0.6).

Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies.

The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs, but also in a high percentage of small-cell lung cancers, stromal ovarian tumors, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies.