Dataset Information

Different uptake patterns of ⁶⁸Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

ABSTRACT:

Background

The diagnosis of a periprosthetic joint infection (PJI) is always a difficult point in research on the surgery of joints. The current diagnostic criteria include a comprehensive analysis of multiple tests; however, there are no effective visual examinations yet that can differentiate between aseptic loosening and the PJI.

Case presentation

This case report describes four patients with symptomatic total hip arthroplasty (THA), two cases of loosening and two cases of infection. Although the four cases were correctly diagnosed by the tissue culture, preoperative tests and pathological examination could not effectively distinguish an infection from a non-infection. Based on a preclinical study and theoretical feasibility, gallium-68 (⁶⁸Ga)-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (⁶⁸Ga-FAPI PET/CT) was performed. Through ⁶⁸Ga-FAPI PET/CT scanning, not only were the causes diagnosed correctly but the lesions were also located.

Conclusion

When the lesion is located between the bone and the prosthesis, ⁶⁸Ga-FAPI PET/CT could differentiate aseptic loosening from periprosthetic joint infection (PJI). ⁶⁸Ga-FAPI PET/CT has clear advantages over routine examinations and has a prospective application in detecting PJI.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9729767 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Different uptake patterns of <sup>68</sup>Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

Wang Yiqun Y Wang Ruimin R Geng Lei L Li Qingxiao Q Qi Erpeng E Shi Yuanyuan Y Wang Yanmei Y Zheng Qingyuan Q Zhang Guoqiang G Chen Jiying J Tian Jiahe J

Frontiers in medicine 20221124

<h4>Background</h4>The diagnosis of a periprosthetic joint infection (PJI) is always a difficult point in research on the surgery of joints. The current diagnostic criteria include a comprehensive analysis of multiple tests; however, there are no effective visual examinations yet that can differentiate between aseptic loosening and the PJI.<h4>Case presentation</h4>This case report describes four patients with symptomatic total hip arthroplasty (THA), two cases of loosening and two cases of infe ...[more]

PMID: 36507508

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Project description:PurposeWe built a joint replacement loosening model based on the original rabbit model of infection and evaluated the performance characteristics of 18F-FDG and 68 Ga-FAPI in evaluating infection and loosening.MethodsAfter surgery, the rabbits were divided into four groups, with six individuals in the control group and 10 each in the aseptic loosening, S. aureus and S. epidermidis groups. PET/CT and serological examination were performed three times at two-week intervals. After the rabbits were euthanized, micro-CT, tissue pathology, pullout tests and scanning electron microscopy (SEM) were performed.ResultsThe pullout test and SEM showed the feasibility of the aseptic loosening model. 18F-FDG showed similar performance in the control and loosening groups. The SUVmax of the S. aureus group was consistently higher than that of the S. epidermidis group. As for 68 Ga-FAPI, the SUVmax of the control group was lowest in the second week and gradually increased over subsequent weeks. The SUVmax of the loosening group began to exceed that of the control group after the second week. The SUVmax of the S. aureus group in the second week was the lowest among the four groups and increased as the number of weeks increased. The pathology results showed concordance with the performance of PET/CT. Linear regressions between SUVmax and serology showed that 18F-FDG was positively correlated with CRP and IL-6, while 68 Ga-FAPI revealed negative correlations with CRP and IL-6 in the second week and positive correlations in the sixth week. In addition, the SUVmax and MT(target)V of both 18F-FDG and 68 Ga-FAPI were negatively correlated with bone volume/trabecular volume (TV) and bone surface area/TV.ConclusionIn this longitudinal observation, 68 Ga-FAPI showed greater sensitivity than 18F-FDG in detecting diseases, and 68 Ga-FAPI had no intestinal or muscular uptake. The MT(target)V of 68 Ga-FAPI was larger than that of 18F-FDG, which meant that 68 Ga-FAPI had the potential to define the scope of lesions more accurately. Finally, the SUVmax of 68 Ga-FAPI could not differentiate between loosening and infection; further study of the diagnostic criteria is warranted.

Project description:Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

Project description:BackgroundThe demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([68Ga]Ga-FAPI-46) in late-phase studies, whereas [68Ga]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach.ResultsDifferent mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 ± 5% for [68Ga]Ga-FAPI-46 and 46 ± 7% for [68Ga]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC were 98.2 ± 0.2% and 98.4 ± 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including 68Ga trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers.ConclusionsThe microfluidic-based approach enabled the implementation of radiosynthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC on the iMiDEV™ microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2-3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [68Ga]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future.

Project description:Purpose68Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer 18F-FDG was performed in selected cases.Patients and methodsA total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent 68Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional 18F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group.ResultsIn 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in 68Ga-FAPI compared to 18F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of 68Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to 18F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed.ConclusionDue to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than 18F-FDG-PET/CT, 68Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.

Dataset Information

Different uptake patterns of ⁶⁸Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

Background

Case presentation

Conclusion

Publications

Different uptake patterns of <sup>68</sup>Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Different uptake patterns of 68Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

Background

Case presentation

Conclusion

Publications

Different uptake patterns of <sup>68</sup>Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Different uptake patterns of ⁶⁸Ga-FAPI in aseptic loosening and periprosthetic joint infection of hip arthroplasty: A case series and literature review.