Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands’ application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.

Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMed/MEDLINE, based on the combination of “PET” OR “positron emission tomography” and “FAPI” and ”cancer”, with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles, ⁶⁸Ga-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients both at staging and restaging, also demonstrating several technical advantages and an overall better performance than ¹⁸F-FDG, especially in histotypes with well-known low ¹⁸F-FDG avidity. Moreover, although with still limited clinical evidence in BC, radiolabeled FAPIs emerge as promising therapeutic agents in a theranostic perspective, increasing the possibility of more personalized treatments. From these results, future research directions on FAPI radiotracers application in BC patients are suggested.

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis.

The prognosis of high-risk neuroblastoma (NB) continues to be poor. The early development of resistance often leads to disease recurrence. In the present study, an innovative induction regimen, including an intensive initial radio-chemotherapy sequence based on the use of iodine-131-metaiodobenzylguanidine (131-I-MIBG), was investigated. The duration of the regimen lasted only one month. Fifteen newly diagnosed patients aged >18 months with high-risk NB were treated with cisplatin, etoposide, cyclophosphamide, and vincristine, followed on day 10 by 131-I-MIBG (dose: 12–18.3 mCi/kg). Cisplatin and vincristine were administered on day 20 and 21 followed by the re-administration of vincristine, cyclophosphamide, and doxorubicin on day 29 and 30. Non-hematologic toxicity was not observed. Moderate hematologic toxicity was present probably attributable to chemotherapy. The evaluation of response was performed approximately 50 days after the initiation of treatment, yielding four complete responses, eight very good partial responses, one partial response, and two non-responses. Importantly, a complete metastatic response was achieved in 87% of patients. The present pilot study, which includes 131-I-MIBG, allows for a highly effective continuous exposure of tumor cells to both chemotherapy and radiotherapy. Furthermore, early high-dose chemotherapy followed by stem cell rescue may achieve high levels of tumor cell clearance and improve the prognosis of high-risk NB.

(1) Background: In ⁹⁰Y-TARE treatments, lung-absorbed doses should be calculated according to the manufacturer’s instructions, using the MIRD-scheme. This scheme is derived from the assumption that ⁹⁰Y-microspheres deliver the dose in a water-equivalent medium. Since the density of the lungs is quite different from that of the liver, the absorbed dose to the lungs could vary considerably, especially at the liver/lungs interface. The aim of this work is to compare the dosimetric results obtained by two dedicated software packages implementing a water-equivalent dose calculation and a Monte Carlo (MC) simulation, respectively. (2) Methods: An anthropomorphic IEC phantom and a retrospective selection of 24 patients with a diagnosis of HCC were taken into account. In the phantom study, starting from a ⁹⁰Y-PET/CT acquisition, the liver cavity was manually fixed with a uniform activity concentration on PET series, while the lung compartment was manually expanded on a CT series to simulate a realistic situation in which the liver and lungs are adjacent. These steps were performed by using MIM ⁹⁰Y SurePlan. Then, a first simulation was carried out with only the liver cavity filled, while a second one was carried out, in which the lung compartment was also manually fixed with a uniform activity concentration corresponding to 10% lung shunt fraction. MIM ⁹⁰Y SurePlan was used to obtain Voxel S-Value (VSV) approach dose values; instead, Torch was used to obtain MC approach dose values for both the phantom and the patients. (3) Results: In the phantom study, the percentage mean dose differences (∆D%) between VSV and MC in the first and second simulation, respectively were found to be 1.2 and 0.5% (absolute dose variation, ∆D, of 0.7 and 0.3 Gy) for the liver, −56 and 70% (∆D of −0.3 and −16.2 Gy) for the lungs, and −48 and −60% (∆D of −4.3 and −16.5 Gy) for the Liver/Lungs Edge region. The patient study reports similar results with ∆D% between VSV and MC of 7.0%, 4.1% and 6.7% for the whole liver, healthy liver, and tumor, respectively, while the result was −61.2% for the left lung and −61.1% for both the right lung and lungs. (4) Conclusion: Both VSV and MC allowed accurate radiation dose estimation with small differences (50%) were observed for air-equivalent regions in the phantom simulation and the patient study.