Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial.

BACKGROUND: [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management. METHODS AND DESIGN: Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting. DISCUSSION: To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response. TRIAL REGISTRATION: clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.

How to Perform FAPI PET? An Expedited Systematic Review Providing a Recommendation for FAPI PET Imaging With Different FAPI Tracers.

This expedited systematic review aims to provide the first overview of the different Fibroblast activation protein inhibitor (FAPI) PET scan procedures in the literature and discuss how to efficiently obtain optimal FAPI PET images based on the best available evidence. The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched in April 2023. Peer-reviewed cohort studies published in English and used FAPI tracers were included. Articles were excluded if critical scan procedure information was missing, or the article was not retrievable from a university library within 30 days. Data were grouped according to the FAPI tracer applied. Meta-analysis with proper statistics was deemed not feasible based on a pilot study. A total of 946 records were identified. After screening, 159 studies were included. [68Ga]Ga-FAPI-04 was applied in 98 studies (61%), followed by [68Ga]Ga-FAPI-46 in 19 studies (12%). Most studies did not report specific patient preparation. A mean/median administered activity of 80-200 MBq was most common; however, wide ranges were seen in [68Ga]Ga-FAPI-04 PET studies (56-370 MBq). An injection-to-scan-time of 60 minutes was dominant for all FAPI PET studies. A possible trend toward shorter injection-to-scan times was observed for [68Ga]Ga-FAPI-46. Three studies evaluated [68Ga]Ga-FAPI-46 PET acquisition at multiple time points in more than 593 cancer lesions, all yielding equivalent tumor detection at 10 minutes vs later time points despite slightly lower tumor-to-background Ratios. Despite the wide ranges, most institutions administer an average of 80-200 MBq [68Ga]Ga-FAPI-04/46 and scan patients at 60 minutes postinjection. For [68Ga]Ga-FAPI-46, the present evidence consistently supports the feasibility of image acquisition earlier than 30 minutes. Currently, data on the optimal FAPI PET scan procedure are limited, and more studies are encouraged. The current review can serve as a temporary guideline for institutions planning FAPI PET studies.

Frequency of superscan on bone scintigraphy: A systematic review.

INTRODUCTION: Bone scintigraphy (BS) is an important tool for detecting bone metastasis. BS with diffuse increased skeletal radioisotope uptake with absent or faint urinary tract and soft tissue activity is defined as a superscan. In this review, we investigate the different etiologies causing superscan and the reported frequency of superscan among different disease entities. MATERIALS AND METHODS: The search terms were 'bone' AND 'superscan' OR 'superscan' in the PubMed database from 1980 to November 2020. Eligibility criteria included the following: Peer-reviewed studies containing original data using 99mTc-phosphate-analogue BS reporting a superscan pattern. Unretrievable papers, imaging modalities other than BS or with insufficient information to assess the aetiology were excluded. The abstracts of every paper and full texts of potentially eligible papers were assessed independently by three observers. RESULTS: Sixty-seven papers were included (48 case reports and 19 cohort studies). Studies conducted in patients with osteomalacia or skeletal fluorosis revealed superscan in all patients. Other benign causes of superscan were hyperparathyroidism and kidney disease. Among papers with malignant cause, prostate cancer was the most common cause, followed by gastric cancer. The frequency of superscans ranged from 1.3% in a cohort of mixed cancer types up to 2.6% in patients with gastric cancer and up to 23% in a cohort of prostate cancer patients. CONCLUSION: Superscan is most frequently seen in prostate cancer, but numerous other cancers and metabolic bone diseases can cause superscan, which should be kept in mind when encountering an unexpected superscan on BS.

Not All Glittering Bone Lesions Are Gold: A Case of Sclerotic Bone Lesions with Elevated 68 Ga PSMA and 99m Tc HDP Uptake with No Signs of Malignancy.

Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga PSMA PET/CT) outperforms CT and bone scintigraphy in terms of diagnostic accuracy for the primary staging of prostate cancer and has become widely used. However, 68 Ga PSMA uptake is also encountered in nonprostatic tissue. We present a 63-year-old male with newly diagnosed high-risk prostate cancer who underwent bone scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT), which showed inhomogeneous elevated uptake in sclerotic bone lesions in the pelvis. Likewise, 68 Ga PSMA PET/CT revealed inhomogeneous uptake in the same areas. Subsequent biopsy revealed hyperplastic bone marrow without signs of malignancy. The patient underwent radical prostatectomy, and the prostate-specific antigen level dropped to less than 0.1 ng/mL.

FAPI-avid nonmalignant PET/CT findings: An expedited systematic review.

Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported. A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with 68Ga or 18F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.

Prevalence and significance of incidental findings on 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT: a systematic review of the literature.

AIM: We aimed to evaluate the prevalence of incidental 68 Ga-DOTA-conjugated somatostatin receptor-targeting peptide PET/CT (SSTR PET/CT) findings, their clinical significance in the need for follow-up, and their risk of malignancy. MATERIALS AND METHODS: Studies reporting incidental SSTR PET/CT findings were systematically searched in PubMed, Cochrane, Embase and Web of Science literature published prior to 1st of May 2020. Studies were filtered by two independent readers for eligibility based on title and abstract, and subsequently on full text. The main exclusion criteria were: 1) pathological findings that matched scan indication, 2) known organ specific disease and/or incidental findings confirmed on other scan modality prior to SSTR PET/CT, 3) lack of diagnosis and/or follow up, and 4) results published in proceedings or conference abstracts. RESULTS: Twenty-one studies, comprising a total of 2906 subjects, were eligible for the analysis. Studies included were retrospective cohort studies on incidental SSTR PET/CT findings in a specific organ (n = 2888, 7/21) or case reports (n = 18, 14/21). A total of 133 subjects had incidental SSTR PET/CT findings. Incidental findings were predominantly seen in the thyroid gland (n = 65), spine (n = 30), brain (n = 26) and breast (n = 6). Seventeen of 133 (13%) incidental findings were malignant on final diagnosis. Incidental breast findings were associated with the highest risk of malignancy (67%). In the thyroid, incidental SSTR uptake was caused by malignancy in 8%, all presenting as focal uptake. The lowest risk was seen in the spine with a malignancy rate of 3% in patients with incidental SSTR uptake and benign cases were interpreted as vertebral hemangiomas on CT. Incidental SSTR PET/CT findings in other locations were of malignant etiology in two out of six cases (33%) and should be evaluated individually. CONCLUSION: The most incidental SSTR PET/CT findings were found in the thyroid gland, spine, and brain. The risk of malignancy was greatest in incidental SSTR PET/CT findings in the breast, cranially, and thyroid gland. The results of the present study can prove useful in the interpretation of atypical findings on SSTR PET/CT and in the counseling of clinicians.