Lung cancer is the second most common cancer and the leading cause of cancer-related death worldwide. Molecular imaging using [¹⁸F]fluorodeoxyglucose Positron Emission Tomography and/or Computed Tomography ([¹⁸F]FDG-PET/CT) plays an essential role in the diagnosis, evaluation of response to treatment, and prediction of outcomes. The images are evaluated using qualitative and conventional quantitative indices. However, there is far more information embedded in the images, which can be extracted by sophisticated algorithms. Recently, the concept of uncovering and analyzing the invisible data extracted from medical images, called radiomics, is gaining more attention. Currently, [¹⁸F]FDG-PET/CT radiomics is growingly evaluated in lung cancer to discover if it enhances the diagnostic performance or implication of [¹⁸F]FDG-PET/CT in the management of lung cancer. In this review, we provide a short overview of the technical aspects, as they are discussed in different articles of this special issue. We mainly focus on the diagnostic performance of the [¹⁸F]FDG-PET/CT-based radiomics and the role of artificial intelligence in non-small cell lung cancer, impacting the early detection, staging, prediction of tumor subtypes, biomarkers, and patient's outcomes.

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.

Prostate cancer with NED (neuroendocrine differentiation) may occur in various stages of the disease, which is associated with a poor prognosis and treatment resistance. We present a case of a patient with metastatic castration-resistant prostatic cancer, who was treated with 7 cycles of ¹⁷⁷Lu-PSMA and a very good response. Although only few foci with PSMA uptake were remained in the last posttreatment images, PSA levels dramatically began to rise. This raised suspicion for NED, and ⁶⁸Ga-DOTATATE was done showing sufficient uptake to consider a trial of ¹⁷⁷Lu-DOTATATE. The patient reported pain response, and PSA levels dropped after 1 cycle of the treatment.

Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through “Darwinian” treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.

We report the case of a 62-year-old man with metastatic castration-resistant prostate cancer with subcutaneous involvement being treated with ¹⁷⁷Lu–prostate-specific membrane antigen (PSMA). Before treatment, he was diagnosed with 2 subcutaneous nodules in the chest wall and soft tissue edema in the pubic and inguinal regions showing PSMA avidity. Biopsy and immunohistochemistry assessment confirmed cutaneous metastases from prostate cancer. He received 3 cycles of ¹⁷⁷Lu-PSMA, resulting in a decline in PSA levels and resolution of symptoms. This case underscores the challenging diagnosis of cutaneous metastasis from prostate cancer, especially in atypical presentations. We also reviewed all causes of PSMA-avid lesions in the skin and subcutaneous tissues.