Tumor diagnosis with different tracers

LAFOV PET-CT scanners allow for the first time whole body pharmacokinetic studies with only one measurement. This means that an evaluation of radiotracer kinetics of all organs can be performed simultaneously. Especially in patients with extended metastatic disease, it is for the first time possible to measure simultaneously the tracer uptake in practically all tumor lesions and all organs. This aspect is important particularly for therapy monitoring, drug development and investigation of possible interactions between different organs, known as connectomes.

Receptor-active peptides enable both the diagnosis and therapy of receptor-active tumors and are used in theragnostic approaches. One of the first examples was [⁶⁸Ga]Ga-DOTA-TOC, a tracer that binds to somatostatin receptor 2 (SSTR2)-expressing tumors, such as neuroendocrine carcinomas or meningiomas, and is also used for therapy in DOTA-TOC-positive tumors labeled with beta emitters as ⁹⁰Y or ¹⁷⁷Lu. Another example of PRRT are PSMA compounds, which bind to PSMA, a cell surface protein, that is enhanced in prostate carcinoma. The first PSMA used for diagnosis was [⁶⁸Ga]Ga-PSMA-11, followed by [¹⁸F]PSMA-1007. The introduction of these new tracers improved the detection of tumor recurrence and staging of prostate cancer by detecting unknown metastatic lesions with a high contrast to the surrounding tissue. Examples of WB pharmacokinetic studies with both PSMA tracers are presented in Fig. 1a and 1b.

Most PET radiopharmaceuticals used in the past targeted more or less different metabolic pathways of the tumor cells. The extraordinary advances in immunotherapy have opened a new era for tracers which target the tumor microenvironment (TME). A novel approach TME is the use of fibroblast activation protein inhibitor (FAPI) imaging in oncological patients, as FAP is known to be overexpressed in the cancer-associated fibroblasts (CAF) of many solid tumors. Several FAPI analogues are available up to now, labeled with ⁶⁸Ga or ¹⁸F, such as [⁶⁸Ga]Ga-FAPI-46 and [¹⁸F]F-FAPI-74. Initial results demonstrate that FAPI may be superior in tumors with low [¹⁸F]FDG uptake.

We focus on esophageal cancer and aim to evaluate and compare dynamic PET-CT studies with [⁶⁸Ga]Ga-FAPI-46 and [¹⁸F]FDG Fig. 2a, 2b, 2c).

Cooperation with the Radiation Department of the UKHD (Prof. Dr. Dr. J. Debus) and the Nuclear Department of the University of Mainz (Prof. Dr. M. Schreckenberger).

The results of whole-body dynamic FDG PET-CT will be compared with those of diffusion-weighted Imaging (DWI) and perfusion-weighted (PWI)-MRI. The comparison of FDG-avid tumor components with diffusion restrictions and pharmacokinetic FDG parameters with PWI-MRI should help in tumor differentiation. Imaging parameters will be correlated to clinicopathological findings in order to explore further imaging characterization. In particular, the identification of aggressive tumor components in the often heterogeneous soft tissue sarcomas is useful before a planned biopsy, as these poorly differentiated areas determine the highest grading and biological behavior of the tumor.

Cooperation with the Radiology of the UKHD (Prof. Dr. U.-H. Kauczor).

We compared both hybrid modalities in patients with recurrent prostate cancer and could demonstrate that prostate-bed multiparametric MRI (mpMRI) improves the detection of [⁶⁸Ga]Ga -PSMA-11 PET-negative local recurrences in a subgroup of prostate recurrencies close to the bladder, which have been superimposed by bladder radioactivity. Hence, the present study demonstrates additional value of hybrid [⁶⁸Ga]Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to [⁶⁸Ga]Ga-PSMA-11-PET/CT low-dose in a subgroup of patients with local recurrences very close to the bladder.

Cooperation with the Radiology of the DKFZ (Prof. Dr. Heinz-Peter Schlemmer).