[^99mTc]Tc-iFAP/SPECT Tumor Stroma Imaging: Acquisition and Analysis of Clinical Images in Six Different Cancer Entities

• Main Authors: Paola Vallejo-Armenta (Author), Guillermina Ferro-Flores (Author), Clara Santos-Cuevas (Author), Francisco Osvaldo García-Pérez (Author), Pamela Casanova-Triviño (Author), Bayron Sandoval-Bonilla (Author), Blanca Ocampo-García (Author), Erika Azorín-Vega (Author), Myrna Luna-Gutiérrez (Author)
• Format: Book
• Published: MDPI AG, 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Fibroblast activation protein (FAP) is highly expressed on the cancer-associated fibroblasts (CAF) of the tumor stroma. Recently, we reported the preclinical evaluation and clinical biokinetics of a novel ^99mTc-labeled FAP inhibitor radioligand ([^99mTc]Tc-iFAP). This research aimed to evaluate [^99mTc]Tc-iFAP for the tumor stroma imaging of six different cancerous entities and analyze them from the perspective of stromal heterogeneity. [^99mTc]Tc-iFAP was prepared from freeze-dried kits with a radiochemical purity of 98 ± 1%. The study included thirty-two patients diagnosed with glioma (<i>n</i> = 5); adrenal cortex neuroendocrine tumor (<i>n</i> = 1); and breast (<i>n</i> = 21), lung (<i>n</i> = 2), colorectal (<i>n</i> = 1) and cervical (<i>n</i> = 3) cancer. Patients with glioma had been evaluated with a previous cranial MRI scan and the rest of the patients had been involved in a [¹⁸F]FDG PET/CT study. All oncological diagnoses were corroborated histopathologically. The patients underwent SPECT/CT brain imaging (glioma) or thoracoabdominal imaging 1 h after [^99mTc]Tc-iFAP administration (i.v., 735 ± 63 MBq). The total lesions (<i>n</i> = 111) were divided into three categories: primary tumors (PT), lymph node metastases (LNm), and distant metastases (Dm). [^99mTc]Tc-iFAP brain imaging was positive in four high-grade WHO III-IV gliomas and negative in one treatment-naive low-grade glioma. Both [^99mTc]Tc-iFAP and [¹⁸F]FDG detected 26 (100%) PT, although the number of positive LNm and Dm was significantly higher with [¹⁸F]FDG [82 (96%)], in comparison to [^99mTc]Tc-iFAP imaging (35 (41%)). Peritoneal carcinomatosis lesions in a patient with recurrent colorectal cancer were only visualized with [^99mTc]Tc-iFAP. In patients with breast cancer, a significant positive correlation was demonstrated among [^99mTc]Tc-iFAP uptake values (Bq/cm³) of PT and the molecular subtype, being higher for subtypes HER2+ and Luminal B HER2-enriched. Four different CAF subpopulations have previously been described for LNm of breast cancer (from CAF-S1 to CAF-S4). The only subpopulation that expresses FAP is CAF-S1, which is preferentially detected in aggressive subtypes (HER2 and triple-negative), confirming that FAP+ is a marker for poor disease prognosis. The results of this pilot clinical research show that [^99mTc]Tc-iFAP SPECT imaging is a promising tool in the prognostic assessment of some solid tumors, particularly breast cancer.

Item Description

10.3390/ph15060729
1424-8247