Several recent studies comparing radiolabeled fibroblast activation protein inhibitors (FAPI) and fluorine-18 fluorodeoxyglucose ([¹⁸F]F-FDG) as positron emission tomography (PET) radiotracers in oncology have been published. The aim of this systematic review is to perform an updated evidence-based summary about the comparison of these PET radiotracers in oncology to better address further research in this setting. Studies or subsets of studies comparing radiolabeled FAPI and [¹⁸F]F-FDG as PET radiotracers in oncology were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until August 2021. Literature data about the comparison of [¹⁸F]F-FDG and radiolabeled FAPI are rapidly increasing. Overall, taking into account radiotracer uptake and tumor-to-background uptake ratio, compared to [¹⁸F]F-FDG PET, an equal or higher detection of primary tumors and/or metastatic lesions was usually demonstrated by using radiolabeled FAPI PET. In particular, the cancer entities with better detection rate of tumor lesions by using radiolabeled FAPI PET, compared to [¹⁸F]F-FDG PET, were gastrointestinal tumors, liver tumors, breast cancer and nasopharyngeal carcinoma. Further comparison studies are needed to better evaluate the best field of application of radiolabeled FAPI PET.

Background. Cancer‐associated fibroblasts (CAFs) can strongly modulate the response to therapy of malignant tumor cells, facilitating their continuous proliferation and invading behaviors. In this context, several efforts were made in identifying the fibroblast activation protein (FAP) as a CAF recognizer and in designing FAP‐specific PET radiotracers (as ⁶⁸Ga‐FAPI) along with FAP‐specific therapeutic radioligands. Herein, we review different clinical studies using the various FAP‐specific radioligands as novel theranostic agents in a wide range of oncologic and nononcologic indications. Methods. A comprehensive systematic search was conducted on the PubMed and Scopus databases to find relevant published articles concerning the FAP‐specific PET imaging as well as the FAP‐specific radionuclide therapy in patients with oncologic and nononcologic indications. The enrolled studies were dichotomized into oncologic and nononcologic categories, and the required data were extracted by precisely reviewing the whole text of each eligible study. A meta‐analysis was also performed comparing the detection rates of ⁶⁸Ga‐FAPI vs. ¹⁸F‐FDG PET/CT using odds ratio (OR) and risk difference as outcome measures. Results. Of the initial 364 relevant papers, 49 eligible articles (1479 patients) and 55 case reports were enrolled in our systematic review. These studies observed high radiolabeled FAPI avidity as early as 10 minutes after administration in primary sites of various malignant tumors. Based on the meta‐analysis which was done on the reported detection rates of the ⁶⁸Ga‐FAPI and ¹⁸F‐FDG PET/CT scans, the highest OR belonged to the primary lesion detection rate of gastrointestinal tumors (OR = 32.079, 95% CI: 4.001–257.212; p = 0.001) with low heterogeneity (I² = 0%). The corresponding value of the nodal metastases belonged to hepatobiliary tumors (OR = 11.609, 95% CI: 1.888–71.365; p = 0.008) with low heterogeneity (I² = 0%). For distant metastases, the highest estimated OR belonged to nasopharyngeal carcinomas (OR = 77.451, 95% CI: 7.323–819.201; p < 0.001) with low heterogeneity (I² = 0%). Conclusions. The outperformance of ⁶⁸Ga‐FAPI PET/CT over ¹⁸F‐FDG PET/CT in identifying certain primary tumors as well as in detecting their metastatic lesions may open indications for evaluation of cases with inconclusive ¹⁸F‐FDG PET/CT findings. What needs to be emphasized is that the false‐positive results might be problematic and must be taken into account in ⁶⁸Ga‐FAPI PET/CT interpretation. More clarification on the role of FAPI radioligands in oncologic imaging, radionuclide therapy, and radiotherapy treatment planning is therefore required.

Background/Objectives: The superscan pattern is a characteristic finding on bone scintigraphy, associated with a variety of metabolic bone diseases, malignancies, and other conditions. This pattern is characterized by a diffuse and intense uptake of radiotracer throughout the entire skeleton. Despite being a relatively rare finding, the superscan pattern can have significant clinical implications. Methods: This comprehensive review summarizes the available literature on the superscan pattern, focusing on its pathophysiology, clinical significance, and differential diagnoses. Relevant studies and case reports were analyzed to outline the diagnostic challenges associated with the interpretation of bone scintigraphy featuring the superscan pattern. Results: The literature highlights the clinical significance of the superscan pattern in various metabolic and oncologic conditions. Misinterpretation of this pattern can lead to diagnostic challenges, especially in distinguishing it from other pathologic conditions. Differential diagnosis remains crucial in the accurate interpretation and subsequent management of patients with this finding. Conclusions: This review provides a comprehensive overview of the superscan pattern on bone scintigraphy, aiming to assist clinicians in recognizing and managing this rare yet clinically important finding.

This paper contains single-center prospective information showing illustrative examples of chemokine receptor-4 (CXCR4) targeting in high-grade glial brain tumors in treatment-naïve adult patients using a novel radiolabeled PET tracer: [⁶⁸Ga]Ga-CXCR4 PET/CT. High-grade glioma is one of the most resistant malignancies to treatment. Despite major breakthroughs in diagnostic and therapeutic approaches, the overall 5-year survival rate remains in the 5-10% range. CXCR4 is a chemokine with the C-X-C motif that is overexpressed in high-grade gliomas. The 24 consecutive treatment- naïve enrolled patients underwent PET/CT images using the SIEMENS scanner (Biograph6 TrueV) and received the radiotracer intravenously. After approximately 60 min, the PET/CT acquisition was performed with a dedicated scanner and in 10 min time per bed position. The images were reconstructed and analyzed with the 3D-OSEM algorithm, applying point spread function (PSF) or resolution recovery algorithm (TrueX in Syngo ® software, Siemens Medical Solution), 3 iterations, and 21 subsets using a 3 mm Gaussian post-smoothing filter. These data would be potentially beneficial for automatic tumor delineation machine learning after augmented with other data retrieved from different papers as well as for differentiation between an active viable tumor vs. post-surgery/necrosis in indeterminate cases. The theranostics potential (CXCR4-tageted labeled beta emitters) is one of the most novel areas of interest for future studies.

Purpose: This review aims to collect the available documents on the clinical safety of Ac-225 radiopharmaceuticals targeted alpha radionuclide therapy and summarize practical safety data recommended for clinical development of Ac-225 radiopharmaceuticals. Methods: A comprehensive literature search was conducted using two bibliographic databases, ClinicalTrials.gov and PubMed/MEDLINE. The search was constructed using the following terms: (A) “Actinium” OR “Ac-225” OR “225Ac” OR “[225Ac]Ac” AND (B) “safety” OR “toxicity” OR “side-effect”. Results: This review included 42 studies. Most of the studies looked at prostate cancer (24 studies), while fewer studies (10 studies) explored neuroendocrine tumors. Emerging targets such as FAP (3 studies), DOTA-substance P (2 studies), DOTA-LM3, Rosopatamab Tetraxetan, and Lintuzumab (each 1 study) were also examined. The most frequently reported adverse events -based on CTCAE v5.0 were hematotoxicity, renal toxicity, and xerostomia, followed by fatigue, weight loss, loss of appetite, and nausea. Renal toxicity was less frequent compared to xerostomia (seen in PSMA therapy) and hematologic events, with severe renal toxicity (grade 3/4) reported in a limited number of patients, particularly those with baseline renal impairment. Several studies highlighted no cases of serious acute adverse events or treatment discontinuation due to adverse events. Conclusions: In summary, the literature indicates a high safety profile with acceptable toxicity for Ac-225 based TAT. This paper provides, to the best of our knowledge, the most comprehensive clinical information on safety of TAT with different Ac-225 radiopharmaceuticals, in different cancer patients until today. Data in the coming years will certainly strengthen the knowledge of short- and long-term toxicities and would facilitate risk-benefit assessments.