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 (n = 5); adrenal cortex neuroendocrine tumor (n = 1); and breast (n = 21), lung (n = 2), colorectal (n = 1) and cervical (n = 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 (n = 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.

Prostate cancer is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of PSMA imaging with PET/CT over conventional imaging for primary diagnoses. Single photon emission computed tomography is more available worldwide, and the imaging agent is low in cost. The aim of this study is to compare the diagnostic accuracy of ^99mTc-EDDA/HYNIC-iPSMA SPECT/CT to ¹⁸F-PSMA-1007 PET/CT in the primary diagnosis of prostate cancer and the impact on clinical staging. Methods: In this prospective controlled study, 18 patients with histologically confirmed prostate cancer with unfavorable intermediate-, high-, and very high-risk characteristics were recruited to undergo ¹⁸F-PSMA-PET/CT and ^99mTc-iPSMA SPECT/CT. The median age of the patients was 71 years old, and the median PSA level was 23.3 ng/mL. Lesions were divided into the prostate, seminal vesicles, lymph nodes, bone, and visceral metastases. Volumetric analysis was also performed between the two imaging modalities and correlated with PSA levels. Results: A total of 257 lesions were detected on ¹⁸F-PSMA-PET/CT: prostate (n = 18), seminal vesicles (n = 12), locoregional lymph nodes (n = 62), non-locoregional (n = 67), bone (n = 90), and visceral (n = 8). Of these, ^99mTc-iPSMA-SPECT/CT detected 229 lesions, while both reviewers detected 100% of the lesions in the prostate (18/18), seminal vesicles (12/12), and visceral (8/8); LN LR (56/62; 90%), NLR (57/67; 85%), and bone (78/90; 86%). There were no statistically significant differences between volumetric parameters (t = −0.02122; p = 0.491596). Conclusions: ^99mTc-iPSMA SPECT/CT is useful in the primary diagnosis of prostate cancer. Despite it showing a slightly lower lesion detection rate compared to ¹⁸F-PSMA PET/CT, it exhibited no impact on clinical staging and, consequently, the initial treatment intention.

Thyroid cancer is a common endocrinological malignancy worldwide, accounting for 3% of the global incidence of all cancers. Meta-analyses, systematic reviews, and descriptive reviews mention the use of positron emission tomography / computed tomography (PET/CT) as an alternative to morphological imaging such as computed tomography or magnetic resonance imaging to clarify the diagnosis. The aim: analysis of positron emission tomography/computed tomography tracers in the differential diagnosis of thyroid carcinomas. Materials and methods: Review about PET/CT tracers different than 2-[18F] fluorodeoxyglucose (FDG) in patients with diagnosed differentiated thyroid carcinoma. Evidence Synthesis: PET/CT is an alternative to morphological diagnosis imaging when is inconclusive or negative due to the suspicion of tumor persistence or recurrence, elevation of tumor markers, dedifferentiation thyroid carcinoma, non-conventional therapeutic options. 2-[18F] FDG is the most uses a tracer, but there are scenarios where can be negative or inconclusive, for this reason, in recent years other PET tracers have been used: [124I] NaI, [18F] Tetrafluoroborate, [68Ga] Ga-NOTE-PRGD2 or [18F] AIF-NOTE-PRGD2, [68Ga] Ga-DOTA-FAPI, [18F] Fluorocholine or [11C] C-Choline, [18F] or [68Ga] Ga-PSMA, [68Ga] Ga DOTA-TATE/TOC/NOC/LAN, [18F]-FAZA, L-[methyl-11C] Methionine and [89Zr] DFO-PAS200-Fab. Conclusions. There are multiple radiopharmaceuticals different than 2-[18F] FDG, which can be adequate in the context of differentiated thyroid carcinoma: 2-[18F] FDG PET/CT negative, TENIS syndrome, radioiodine-refractory thyroid cancer suspected, thyroid dedifferentiated carcinoma, and some cases theragnostic tools.