Current Radiopharmaceuticals - Volume 13, Issue 1, 2020

Background: 18F-FDG PET/CT has been suggested as an effective tool to stage patients affected by melanoma. In the latest years, new radiopharmaceuticals have been proposed and the use of hybrid PET/ceCT has emerged. Objective: To review recent evidence on the role of PET/CT in melanoma staging as well as its potential for future developments. Methods: A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the feasibility of PET/CT in patients with malignant melanoma. Results: Some recent studies about potentials and limitations of 18F-FDG PET/CT in staging melanoma, new PET radiotracers beyond 18F-FDG and application of hybrid PET/ceCT have been reviewed and discussed. Conclusion: PET/CT plays an important role in the staging workup of patients affected by melanoma. New radiopharmaceuticals and hybrid PET/ceCT could improve the potential of this diagnostic tool in this field.

Background: Cutaneous malignant melanoma is a neoplasm whose incidence and mortality are dramatically increasing. 18F-FDG PET/CT gained clinical acceptance over the past 2 decades in the evaluation of several glucose-avid neoplasms, including malignant melanoma, particularly for the assessment for distant metastases, recurrence and response to therapy. Objective: To describe the advancements of nuclear medicine for imaging melanoma with particular attention to 18F-FDG-PET and its current state-of-the-art technical innovations. Methods: A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the articles that evaluated the technological insights of 18FFDG- PET in the assessment of melanoma. Results: State-of-the-art silicon photomultipliers based detectors (“digital”) PET/CT scanners are nowadays more common, showing technical innovations that may have beneficial implications for patients with melanoma. Steady improvements in detectors design and architecture, as well as the implementation of both software and hardware technology (i.e., TOF, point spread function, etc.), resulted in significant improvements in PET image quality while reducing radiotracer dose and scanning time. Conclusion: Recently introduced digital PET detector technology in PET/CT and PET/MRI yields higher intrinsic system sensitivity compared with the latest generation analog technology, enabling the detection of very small lesions with potential impact on disease outcome.

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Method: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.

Background: Melanoma is the most lethal skin cancer with a mortality rate of 262 cases per 100.000 cases. The sentinel lymph node (SLN) is the first lymph node draining the tumor. SLN biopsy is a widely accepted procedure in the clinical setting since it provides important prognostic information, which helps patient management, and avoids the side effects of complete lymph node dissection. The rationale of identifying and removing the SLN relies on the low probability of subsequent metastatic nodes in case of a negative histological exam performed in the SLN. Discussion: Recently, new analytical approaches, based on the evaluation of scintigraphic images are also exploring the possibility to predict the metastatic involvement of the SLN. 99mTc-labeled colloids are still the most commonly used radiotracers but new promising radiotracers, such as 99mTc- Tilmanocept, are now on the market. In the last decades, single photon emission computed tomography- computerized tomography (SPECT/CT) has gained wider diffusion in clinical departments and there is large evidence about its superior diagnostic accuracy over planar lymphoscintigraphy (PL) in the detection of SLN in patients with melanoma. Scientists are also investigating new hybrid techniques combining functional and anatomical images for the depiction of SLN but further evidence about their value is needed. Conclusion: This review examined the predictive and prognostic factors of lymphoscintigraphy for metastatic involvement of SLN, the currently available and emerging radiotracers and the evidence of the additional value of SPECT/CT over PL for the identification of SLN in patients with melanoma. Finally, the review discussed the most recent technical advances in the field.

Background: Several studies on 18F-FDG-PET/CT have investigated the prognostic role of this imaging modality in different tumors after treatment. Nevertheless, its role in restaging patients with recurrent CM still needs to be defined. Objective: The aim of this retrospective multicenter study was to evaluate the clinical and prognostic impact of 18F-FDG-PET/CT on the restaging process of cutaneous melanoma (CM) after surgery in patients with suspected distant recurrent disease or suspected metastatic progression disease. Materials and Methods: 74 patients surgically treated for CM underwent 18F-FDG-PET/CT for suspected distant recurrent disease or suspected metastatic progression disease. The diagnostic accuracy of visually interpreted 18F-FDG-PET/CT was obtained by considering histology (n=21 patients), other diagnostic imaging modalities performed within 2 months of PET/CT (CT in 52/74 patients and Whole-Body MRI in 18/74 patients) and clinical follow-up (n=74 patients) for at least 24 months containing all the clinical and diagnostic information useful for the PET performance assessment and outcome. Progression-free survival (PFS) and overall survival (OS) were assessed by using the Kaplan- Meier method. The risk of progression (Hazard Ratio-HR) was computed by the Cox regression analysis. Results: Suspicion of recurrent CM was confirmed in 24/27 patients with a positive 18F-FDG-PET/CT scan. Overall, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG-PET/CT were 82%, 93%, 88%, 89%, and 89%, respectively, with area under the curve being 0.87 (95%IC 0.78-0.97; p<0.05). 18F-FDG-PET/CT findings significantly influenced the therapeutic management in 18 patients (modifying therapy in 10 patients; guiding surgery in 8 patients). After 2 years of follow-up, PFS was significantly longer in patients with a negative vs. a positive 18F-FDG-PET/CT scan (90% vs 46%, p<0.05; Fig. 1). Moreover, a negative scan was associated with a significantly longer OS than a positive one (76% vs 39% after 2 years, p<0.05; Fig. 2). In addition, a positive 18F-FDG-PET/CT scan was associated with an increased risk of disease progression (HR=8.2; p<0,05). Conclusion: 18F-FDG-PET/CT showed a valuable diagnostic performance in patients with suspicion of recurrent CM. This imaging modality might have an important prognostic value in predicting the survival outcomes, assessing the risk of disease progression, and guiding treatment decision making.

Background: Cutaneous melanoma is one of the most severe skin diseases. Nodular melanoma is the second melanoma subtype in order of frequency. The prognosis of skin melanoma depends on the vertical growth of the tumor (Breslow index). For this measurement, excisional biopsy is strongly recommended. This is, however, an invasive procedure and may cause damage to the lymphatic drainage system. The HFUS system, , can be extremely useful for determining tumor thickness in the preoperative phase, given its high resolution capacity. The aim of this preliminary study is to define the role of HFUS for the nodular skin melanoma Breslow thickness in adults before surgery by making a comparison with histological features. Methods: In this study, 14 melanocytic lesions (8 male and 6 female) were evaluated with dermatoscopic clinical features strongly indicative of nodular melanoma. Out of these, excisional biopsy of 7 lesions was requested. The ultrasounds were performed preoperatively. The images were acquired through the first ultrasound scanner with ultra-high frequency probes (range from 50MHz to 70 MHz) available on the market under the EEC mark (Vevo "MD, FUJIFILM Visual Sonics, Amsterdam, the Netherlands) equipped with a linear probe of 50-70 MHz. Results: From the ultrasonographic analysis of 14 nodular melanoma thickness was determined for the presence of two hyperechogenic laminae, separated by a hypo / anechoic space. The twelve lesions were in situ while the other two lesions showed ultrasonography for example; the satellite lesions (less than two centimeters from the primary lesion) and in transit (localizable to more than two centimeters from the primary lesion). Four of these lesions were ulcerated. A comparsion was made the 7 lesions on between the thickness calculated with this method, and that obtained on the bioptic piece. The presence of a positive concordance has been evident in all of the cases. Conclusion: If further studies are needed to support its widespread clinical use, its is believed that, in expert hands and with an interdisciplinary team, HFUS is already capable to reliably calculate a Breslow index in a large majority of patients with cutaneous melanoma.

Background: Malignant melanoma frequently spreads to the gastrointestinal tract, with 60% of patients with advanced metastatic disease showing digestive involvement; however, primary MM of the small intestine is a controversial diagnosis. In fact, whether these lesions arise as true small bowel primary neoplasms or represent metastases from unidentified cutaneous melanomas remains debatable. The most common complications are intestinal obstruction, massive gastrointestinal bleeding, and perforation. Objective & Methods: We report a case of a 64-year-old patient, with an unremarkable medical history, in which a late diagnosis of primary ileal malignant melanoma in the setting of an emergency laparotomy due to small bowel obstruction, and where PET-scan showed costal metastasis. Therefore, we provide a narrative review of the scientific literature about this topic. Results: 36 cases of primary small bowel melanoma, included that in the present study, were found through our search in the scientific literature. Conclusion: Primary small bowel MM appears to be an extremely rare entity which clinicians should be more aware of, in order to plan better a correct strategy of early diagnosis and appropriate treatment.

Background: The rising incidence rate of prostate cancer (PCa) has promoted the development of new diagnostic and therapeutic radiopharmaceuticals during the last decades. Promising improvements have been achieved in clinical practice using prostate specific membrane antigen (PSMA) labeled agents, including specific antibodies and small molecular weight inhibitors. Focusing on molecular docking studies, this review aims to highlight the progress in the design of PSMA targeted agents for a potential use in nuclear medicine. Results: Although the first development of radiopharmaceuticals able to specifically recognize PSMA was exclusively oriented to macromolecule protein structure such as radiolabeled monoclonal antibodies and derivatives, the isolation of the crystal structure of PSMA served as the trigger for the synthesis and the further evaluation of a variety of low molecular weight inhibitors. Among the nuclear imaging probes and radiotherapeutics that have been developed and tested till today, labeled Glutamate-ureido inhibitors are the most prevalent PSMA-targeting agents for nuclear medicine applications. Conclusion: PSMA represents for researchers the most attractive target for the detection and treatment of patients affected by PCa using nuclear medicine modalities. [99mTc]MIP-1404 is considered the tracer of choice for SPECT imaging and [68Ga]PSMA-11 is the leading diagnostic for PET imaging by general consensus. [18F]DCFPyL and [18F]PSMA-1007 are clearly the emerging PET PSMA candidates for their great potential for a widespread commercial distribution. After paving the way with new imaging tools, academic and industrial R are now focusing on the development of PSMA inhibitors labeled with alpha or beta minus emitters for a theragnostic application.

Background: 99mTc is a radioactive isotope that is obtained by eluting a 99Mo/99mTc generator. (PINSTECH, Islamabad) and used for radionuclide scanning. Objectives: The objective of this work is to study the uncertainties in 99mTc activity that exist due to time delay between injection preparation and administration to patients, during the process of gamma camera scanning. Methods: Lead canisters were used for storing elution vials and dose calibrator for measuring 99mTc activity in mCi. The activity of preparing 99mTc injection and its administration to patients were compared with the prescribed values of activity recommended in the Society of Nuclear Medicine procedure guidelines. Results: This study showed that uncertainty in the activity existed in one thyroid patient, 38 bone patients, 5 renal patients and 45 cardiac patients. Conclusion: This uncertainty in activity exists due to time delay between injection preparation and administration to patients, as well as due to residual radionuclide that is not injected into patients and remains in the syringe.