(1) Background: As outcome of patients with metastatic melanoma treated with anti-PD1 immunotherapy can vary in success, predictors are needed. We aimed to predict at the patients’ levels, overall survival (OS) and progression-free survival (PFS) after one year of immunotherapy, based on their pre-treatment 18F-FDG PET; (2) Methods: Fifty-six metastatic melanoma patients—without prior systemic treatment—were retrospectively included. Forty-five 18F-FDG PET-based radiomic features were computed and the top five features associated with the patient’s outcome were selected. The analyzed machine learning classifiers were random forest (RF), neural network, naive Bayes, logistic regression and support vector machine. The receiver operating characteristic curve was used to compare model performances, which were validated by cross-validation; (3) Results: The RF model obtained the best performance after validation to predict OS and PFS and presented AUC, sensitivities and specificities (IC95%) of 0.87 ± 0.1, 0.79 ± 0.11 and 0.95 ± 0.06 for OS and 0.9 ± 0.07, 0.88 ± 0.09 and 0.91 ± 0.08 for PFS, respectively. (4) Conclusion: A RF classifier, based on pretreatment 18F-FDG PET radiomic features may be useful for predicting the survival status for melanoma patients, after one year of a first line systemic treatment by immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90–95% of all pancreatic tumors, is a highly devastating disease associated with poor prognosis. The lack of accurate diagnostic tests and failure of conventional therapies contribute to this pejorative issue. Over the last decade, the advent of theranostics in nuclear medicine has opened great opportunities for the diagnosis and treatment of several solid tumors. Several radiotracers dedicated to PDAC imaging or internal vectorized radiotherapy have been developed and some of them are currently under clinical consideration. The functional information provided by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) could indeed provide an additive diagnostic value and thus help in the selection of patients for targeted therapies. Moreover, the therapeutic potential of β^-- and α-emitter-radiolabeled agents could also overcome the resistance to conventional therapies. This review summarizes the current knowledge concerning the recent developments in the nuclear medicine field for the management of PDAC patients.

Background: To assess whether whole-body (WB) bone SPECT/CT provides additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence (PC-BR). Methods: Patients referred for a PC-BR and whom benefited from a WB bone SPECT/CT and FCH PET/CT were retrospectively included. Tests were classified as positive, equivocal, or negative for bone metastases. A best valuable comparator (BVC) strategy including imaging and follow-up data was used to determine the metastatic status in the absence of systematic histological evaluation. Results: Between January 2011 and November 2017, 115 consecutive patients with a PC-BR were evaluated. According to the BVC, 30 patients had bone metastases and 85 patients did not present with bone lesions. The sensitivity, specificity, positive and negative predictive values were respectively 86.7% [69.3–96.2], 98.8% [93.6–100.0], 96.3% [78.7–99.5], and 95.5% [89.4–98.1] for WB bone SPECT/CT and 93.3% [77.9–99.2], 100.0% [95.8–100.0], 100.0 and 97.7% [91.8–99.4] for FCH PET/CT. There was no significant difference in diagnostic accuracy of bone metastases between WB Bone SPECT/CT (AUC 0.824 [0.74–0.90]) and FCH PET/CT (AUC 0.829 [0.75–0.90], p = 0.41). Conclusion: Despite good performances for the diagnosis of bone metastases in PC-BR, WB bone SPECT/CT does not provide additive diagnostic information over concomitant FCH PET/CT.

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using ^99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, ^99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, ^99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of ^99mTc-Ctl (p < 0.05). ^99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.

Background: Soluble oligomeric forms of Tau protein have emerged as crucial players in the propagation of Tau pathology in Alzheimer’s disease (AD). Our objective is to introduce a single-domain antibody (sdAb) named 2C5 as a novel radiotracer for the efficient detection and longitudinal monitoring of oligomeric Tau species in the human brain. Methods: The development and production of 2C5 involved llama immunization with the largest human Tau isoform oligomers of different maturation states. Subsequently, 2C5 underwent comprehensive in vitro characterization for affinity and specificity via Enzyme-Linked Immunosorbent Assay and immunohistochemistry on human brain slices. Technetium-99m was employed to radiolabel 2C5, followed by its administration to healthy mice for biodistribution analysis. Results: 2C5 exhibited robust binding affinity towards Tau oligomers (Kd = 6.280 nM ± 0.557) and to Tau fibers (Kd = 5.024 nM ± 0.453), with relatively weaker binding observed for native Tau protein (Kd = 1791 nM ± 8.714) and amyloid peptide (Kd > 10,000 nM). Remarkably, this SdAb facilitated immuno-histological labeling of pathological forms of Tau in neurons and neuritic plaques, yielding a high-contrast outcome in AD patients, closely mirroring the performance of reference antibodies AT8 and T22. Furthermore, 2C5 SdAb was successfully radiolabeled with 99mTc, preserving stability for up to 6 h post-radiolabeling (radiochemical purity > 93%). However, following intravenous injection into healthy mice, the predominant uptake occurred in kidneys, amounting to 115.32 ± 3.67, 97.70 ± 43.14 and 168.20 ± 34.52% of injected dose per gram (% ID/g) at 5, 10 and 45 min respectively. Conversely, brain uptake remained minimal at all measured time points, registering at 0.17 ± 0.03, 0.12 ± 0.07 and 0.02 ± 0.01% ID/g at 5, 10 and 45 min post-injection respectively. Conclusion: 2C5 demonstrates excellent affinity and specificity for pathological Tau oligomers, particularly in their early stages of oligomerization. However, the current limitation of insufficient blood–brain barrier penetration necessitates further modifications before considering its application in nuclear medicine imaging for humans.

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The ⁶⁸Ga/¹⁷⁷Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, ¹⁷⁷Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for ¹⁷⁷Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of ¹⁷⁷Lu-PSMA-1.