<sup>18</sup>F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis

Perng, Powell; Marcus, Charles; Subramaniam, Rathan M.

doi:10.2214/ajr.14.13575

Cited by 54 publications

(30 citation statements)

References 86 publications

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“…The evaluation of residual tumors and metastasis after immune checkpoint blockade therapy is essential; however, it has been reported that 18 F-fluorodeoxyglucose (FDG) PET/CT readings can be confounded by the presence of inflammatory cells, which mimic tumor FDG uptake. 3 Consistently, FDG PET/ CT demonstrated mimic tumors in several lymph nodes in our case (data not shown). Thus, other diagnostic tools for the evaluation of residual tumor are required.…”

supporting

confidence: 87%

“…1,2 Previous reports speculated that paracrine factors secreted from dermal fibrosis induce proliferation and differentiation of the overlying epidermis. 3 Herein, we present a case of the rare variant of dermatofibroma and performed the first dermoscopic study of the lesion to identify features that can be a dermoscopic clue to the differential diagnosis between typical dermatofibroma and dermatofibroma with overlying sebaceous hyperplasia.…”

Section: Dermoscopic Features Of Dermatofibroma With Overlying Sebacementioning

confidence: 99%

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Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

Yamamura

Otsuka

Kaku

et al. 2016

The Journal of Dermatology

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Effective immune checkpoint blockades have improved the overall survival of patients with metastatic melanoma. The monoclonal antibody nivolumab blocks programmed death-1 (PD-1), an inhibitory immune checkpoint receptor expressed on activated T cells.1 The conventional dermoscopic analysis of tumor lesions, which is based on the recognition of specific criteria, is available as a non-invasive diagnostic technique for melanoma.2 Although various dermoscopic patterns of melanoma have been reported, the dermoscopic patterns of residual melanoma after treatment with nivolumab have not yet been described.A 66-year-old Japanese woman was referred to our hospital for treatment of malignant melanoma on her left chest and metastases in the small intestine (Fig. 1a). Dermoscopic analysis of the skin lesion showed a blue-whitish veil, irregular streaks, scar-like depigmentation and an atypical pigment network (Fig. 1b). Histological analysis of the skin biopsy revealed a nest of neoplastic cells with melanin in the basal layer (Fig. 1c). Extensive regression was visible in the middle of the lesion (Fig. 1a). Positron emission computerized tomography (PET/CT) conducted at a previous hospital showed metastases in the pelvic peritoneum, abdominal lymph nodes, left axillary lymph nodes, left cervical lymph nodes and left erector muscle of the spine. We commenced treatment with nivolumab (2 mg/ kg) every 3 weeks. After two courses of nivolumab, the tumor in the small intestine, the only measurable lesion, had reduced in size by more than 30% compared with baseline. After eight courses of nivolumab, we found that the macule on her left chest had grown pale and a depigmented spot appeared. (Fig. 1d) Dermoscopic analysis showed sporadic and closely spaced peppering inside the depigmented area (Fig. 1e). To

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supporting

confidence: 87%

Section: Dermoscopic Features Of Dermatofibroma With Overlying Sebacementioning

confidence: 99%

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

Yamamura

Otsuka

Kaku

et al. 2016

The Journal of Dermatology

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“…While these tracers are well-studied in cancer, they may be limited by inflammatory responses, infections, and malignant tissues with low FDG avidity 28 . For patients treated with immunotherapies, the infiltration of lymphocytes and reactivation of the immune response will naturally result in some local inflammation, making distinction of response versus progression difficult with these tracers 29 . Hence, these tracers may not be effective for imaging of patient response to immunotherapies and targeting of specific cell surface receptors may provide additional benefit.…”

Section: Discussionmentioning

confidence: 99%

ImmunoPET Imaging of CTLA-4 Expression in Mouse Models of Non-small Cell Lung Cancer

et al. 2017

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Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is expressed on the surface of activated T cells and some tumor cells, and is the target of the clinically-approved monoclonal antibody ipilimumab. In this study, we investigate specific binding of radiolabeled ipilimumab to CTLA-4 expressed by human non-small cell lung cancer cells in vivo using positron emission tomography (PET). Ipilimumab was radiolabeled with 64Cu (t1/2 = 12.7 h) through the use of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to formulate 64Cu-DOTA-ipilimumab. CTLA-4 expression in three non-small cell lung cancer (NSCLC) cell lines (A549, H460, and H358) was verified and quantified by Western blot and enzyme-linked immunosorbent assays (ELISA). A receptor binding assay was utilized to monitor the binding and internalization of 64Cu-DOTA-ipilimumab in the NSCLC cell lines. Next, the biodistribution of 64Cu-DOTA-ipilimumab was mapped by longitudinal PET imaging up to 48 h after injection. Ex vivo biodistribution and histological studies were employed to verify PET results. By in vitro analysis, CTLA-4 was found to be expressed on all three NSCLC cell lines with A549 and H358 showing the highest and lowest level of expression, respectively. PET imaging and quantification verified these findings as the tracer accumulated highest in the A549 tumor model (9.80 ± 0.22 %ID/g at 48 h after injection; n=4), followed by H460 and H358 tumors with uptakes of 9.37 ± 0.26 %ID/g and 7.43 ± 0.05 %ID/g, respectively (n=4). The specificity of the tracer was verified by injecting excess ipilimumab in A549 tumor-bearing mice, which decreased tracer uptake to 6.90 ± 0.51 %ID/g at 48 after injection (n=4). Ex vivo analysis following the last imaging session also corroborated these findings. 64Cu-DOTA-ipilimumab showed enhanced and persistent accumulation in CTLA-4-expressing tissues, which will enable researchers further insight into CTLA-4 targeted therapies in the future.

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“…The vast majority of other available data on the potential utility of 18 F-FDG-PET after ICPIs are case reports more often describing underlying challenges of monitoring radiologic response in these patients and showing 18 F-FDG-PET features of inflammatory reactions. PET-highlighted autoimmune pancolitis, splenic sarcoidosis-like lesion and exacerbation of sarcoidosis as a potential confounder in the assessment of tumor response in a melanoma patient treated with ipilimumab have all been described[25-27]. Similarly, Koo et al[26] illustrated a series of inflammatory reactions with avid FDG uptake in patients treated with ipilimumab, including those with thyroiditis, hypophysitis, granulomatous inflammation in the lymph nodes and skin, and enterocolitis.…”

Section: Textmentioning

confidence: 99%

Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

Bauckneht¹,

Piva²,

Sambuceti³

et al. 2017

WJR

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Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.

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¹⁸F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis

Abstract: FDG PET/CT is useful in staging disease, assessing therapy, and determining prognosis in patients with melanoma.

Cited by 54 publications

References 86 publications

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

ImmunoPET Imaging of CTLA-4 Expression in Mouse Models of Non-small Cell Lung Cancer

Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

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18F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis

Abstract: FDG PET/CT is useful in staging disease, assessing therapy, and determining prognosis in patients with melanoma.

Cited by 54 publications

References 86 publications

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

Dermoscopic changes in malignant melanoma after successful treatment with nivolumab: A case report

ImmunoPET Imaging of CTLA-4 Expression in Mouse Models of Non-small Cell Lung Cancer

Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

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Product

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¹⁸F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted Therapy Assessment, and Prognosis