Seminars in nuclear medicine最新文献

Cardiac amyloidosis (CA) is caused by the misfolding, accumulation and aggregation of proteins into large fibrils in the extracellular compartment of the myocardium, leading to restrictive cardiomyopathy, heart failure and death. The major forms are transthyretin (ATTR) CA and light-chain (AL) CA, based on the respective precursor protein. Each of them requires early diagnosis for a timely treatment initiation that will improve patient outcomes. For this, radionuclide imaging is essentially used as single-photon emission computed tomography (SPECT) with bone-avid radiotracers or as positron emission tomography (PET) with amyloid-binding radiotracers. Both offer unprecedented specificity for the diagnostic of CA. SPECT has even revolutionized the diagnosis of ATTR-CA by making it non-invasive. Indeed, SPECT has now entered the standard diagnostic pathway to CA and has led to earlier diagnosis of the disease. SPECT also modified the epidemiology of ATTR-CA, highlighting that the disease is much more frequent than previously believed, and showing that ATTR-CA plays a substantial role in HFpEF and aortic stenosis, particularly among elderly patients. In parallel, amyloid-binding radiotracers for PET have accumulated a substantial amount of evidence, but are not approved for clinical use in CA yet. Further studies are needed to refine acquisition protocols and validate results in broader populations. Unlike bone-avid SPECT radiotracers, PET radiotracers have been specifically created to bind to amyloid fibrils. Thus, PET is the only imaging method that is truly specific for amyloid deposits and very sensitive to any amyloid type. Indeed, PET can not only detect ATTR-CA, but also AL-CA and rare hereditary forms. For both SPECT and PET, advances in quantitation of myocardial uptake have generated more granular and reproducible findings, paving the way for progress in earlier diagnosis, risk stratification and therapeutic response monitoring. Encouraging findings have shown that SPECT and PET are sensitive to early CA when other diagnostic methods are negative. Both radionuclide imaging techniques can predict adverse outcomes, but more evidence is needed to determine how to use them in conjunction with usual prognostic staging scores. Studies on follow-up imaging after therapy suggested that SPECT and PET can capture myocardial changes in CA, but again, more data are needed to meaningfully interpret such changes. Based on all these promising results, radionuclide imaging has the potential to further impact the landscape of CA in diagnosis, prognosis and follow-up, but also to substantially contribute to the assessment of novel therapies that will improve the lives of patients with CA.

In Greek mythology, The Phoenix is an immortal bird that dies, but then achieves new life by rising from the ashes of its predecessor. Radioimmunotherapy (RIT) of B-cell Non-Hodgkin lymphoma (NHL) is a field which once began to fly high—with FDA approval of the anti-CD20 RITs Zevalin® and Bexxar® in 2002 and 2003 respectively, as safe and effective therapies of NHL. However, despite their therapeutic efficacy, Bexxar® was withdrawn from the market by the manufacturer in 2014 due to limited commercial demand and Zevalin® has had very limited to no availability of late. I-131 rituximab is used to a limited extent in Australia, India and other countries, as well.

But has RIT of NHL been (perhaps prematurely) left for dead by many? Given the current great clinical and commercial interest in radiopharmaceutical therapies of cancer, notably PSMA and SSTR targeting agents in prostate and neuroendocrine cancers, can radioimmunotherapy of NHL—like the mythical Phoenix—now rise from its ashes in an even better form to fly higher, faster, farther and longer than before?

Radiotheranostics, a combination of diagnostic and therapeutic approaches, was first utilized in cancer management using radiopharmaceuticals to both image and selectively treat specific cancer subtypes nearly a century ago. Radiotheranostic strategies rooted in nuclear medicine have revolutionized the treatment landscape for individuals diagnosed with prostate cancer and neuroendocrine tumors in the past 10 years. In specific contexts, these approaches have emerged as the prevailing standard, yielding numerous positive results. The field of radiotheranostics shows great potential for future clinical applications. This article aims to examine the key factors that will contribute to the success of radiotheranostics in the future, as well as the current challenges and potential strategies to overcome them, with insight into the global radiotheranostic market.

Combination models utilising treatments from two or more therapeutic classes are well established in cancer care. In the new era of theranostic (theragnostic) medicine there is an ongoing need to identify and refine novel combination strategies to optimise multidisciplinary care for conditions commonly encountered in nuclear medicine such as neuroendocrine neoplasms (NEN), prostate cancer (PCa), and thyroid cancer, along with seeking advancements in molecular imaging and therapy techniques for other tumour streams. This concise review explores the background of theranostic monotherapy, established approaches to combination strategies in theranostics, and emerging targeted radionuclide therapies in use or under active investigation, with a focus on Australian-led studies.

The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands. This review aims to showcase the promising outcomes and challenges in integrating FAP-targeted approaches into cancer management.

Neuroendocrine neoplasms (NENs), arising from various sites, present therapeutic challenges. Radioligand therapy (RLT) is effective for unresectable/metastatic NENs with increased somatostatin receptor uptake. While evidence supports RLT's efficacy in midgut NETs, its role in lung NETs remains underexplored. Clinical guidelines place RLT as a third or fourth-line option in this setting. However, in the last years several studies investigated mainly retrospectively effectiveness and safety of RLT in lung NET. The aim of this review is to assess the efficacy and safety of RLT in patients with lung NETs. Following PRISMA guidelines, a systematic review of MEDLINE and EMBASE databases retrieved English articles until March 31, 2023. Inclusion criteria encompassed studies involving RLT in lung NETs with efficacy and safety assessments. Twenty-seven studies met the criteria, totaling 786 patients. The pooled analysis revealed a 25.6% objective response rate and 75.6% disease control rate. Median progression-free survival averaged 20 months, while overall survival averaged 45 months. Factors affecting response included tumor burden, prior treatments, ¹⁸F-FDG PET scan uptake, and histological variants. RLT exhibited manageable grade 1/2 adverse effects, predominantly hematological, with Lu¹⁷⁷ demonstrating a more favorable profile than Y⁹⁰. The findings support RLT's effectiveness in lung NETs, offering hope for advanced SSTR-positive patients. Although identifying predictive factors for response remains challenging, RLT retained efficacy even after prior therapies and typical carcinoids displayed a slightly better response than atypical ones. Prospective trials are imperative to establish RLT's definitive efficacy and its place in the therapeutic landscape for lung NETs.

Alpha theranostics offer an attractive alternative form of therapy, which has best been investigated and documented with ²²⁵Ac-PSMA in patients with prostate cancer. Advantages offered by targeted alpha therapy include overcoming radiation resistance, oxygen independence, effecting double-stranded DNA breakages within the tumors with anticipated improved clinical outcomes and an acceptable side effect profile. The previous Seminars article on this topic, published in 2020, had to rely mostly on published case reports and small observational studies. In the last few years, however, several meta-analyses have emerged that evaluate the safety and efficacy of ²²⁵Ac-PSMA in prostate cancer patients, followed most recently by a multi-center retrospective study initiated by WARMTH. The findings of these publications, together with the exploration of TAT offered in clinical conditions other than as a last resort, is the focus of this updated overview. Unresolved clinical issues that remain, include the appropriate selection of patients that would benefit most from treatment with ²²⁵Ac-PSMA, treatment timing within the disease landscape, optimal dosing schedule, dosimetry, when and how to best use combination therapies and minimization and treatment of side effects, particularly that of xerostomia.

Molecular imaging is pivotal in evaluating and managing patients with different thyroid cancer histotypes. The existing, pathology-based, risk stratification systems can be usefully refined, by incorporating tumor-specific molecular and molecular imaging biomarkers with theranostic value, allowing patient-specific treatment decisions. Molecular imaging with different radioactive iodine isotopes (ie, I¹³¹, I¹²³, I¹²⁴) is a central component of differentiated carcinoma (DTC)'s risk stratification while [¹⁸F]F-fluorodeoxyglucose ([¹⁸F]FDG) PET/CT is interrogated about disease aggressiveness and presence of distant metastases. Moreover, it is particularly useful to assess and risk-stratify patients with radioiodine-refractory DTC, poorly differentiated, and anaplastic thyroid cancers. [¹⁸F]F-dihydroxyphenylalanine (6-[¹⁸F]FDOPA) PET/CT is the most specific and accurate molecular imaging procedure for patients with medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells. In addition, [¹⁸F]FDG PET/CT can be used in patients with more aggressive clinical or biochemical (ie, serum markers levels and kinetics) MTC phenotypes. In addition to conventional radioiodine therapy for DTC, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC. Moreover, peptide receptor theranostics showed promising results in patients with advanced and metastatic radioiodine-refractory DTC and MTC, respectively. The current appropriate role and future perspectives of molecular imaging and theranostics in thyroid cancer are discussed in our present review.

Radiopharmaceutical approaches for targeting bone metastasis have traditionally focused on palliation of pain. Several agents have been clinically used over the last several decades and have proven value in pain palliation providing pain relief and improving quality of life. The role is well established across several malignancies, most commonly used in osteoblastic prostate cancer patients. These agents have primarily based on targeting and uptake in bone matrix and have mostly included beta emitting isotopes. The advent alpha emitter and FDA approval of 223Ra-dichloride has created a paradigm shift in clinical approach from application for pain palliation to treatment of bone metastasis. The approval of 223Ra-dichloride given the survival benefit in metastatic prostate cancer patients, led to predominant use of this alpha emitter in prostate cancer patients. With rapid development of radiopharmaceutical therapies and approval of other targeted agents such as 177Lu-PSMA the approach to treatment of bone metastasis has further evolved and combination treatments have increasingly been applied. Novel approaches are needed to improve and expand the use of such therapies for treatment of bone metastasis. Combination therapies with different targeting mechanisms, combining chemotherapies and cocktail of alpha and beta emitters need further exploration.

Selective intra-arterial radiotherapy (SIRT) is a technique which has evolved over the past 30 years. In present this is primarily used to treat primary and secondary tumors in the liver. The technique normally depends on the delivery of a therapeutic radiopharmaceutical or radiolabeled particulate via a radiologically placed intra-arterial catheter in the hepatic artery. This is because most of these tumors have a single arterial blood supply but normal hepatocytes are supplied by both the hepatic artery and portal vein. Initially, this was done with I-131 labelled poppy seed oil but this technique was only used in a few centers. The technique became more popular when Y-90 particulates become widely available. Early results were promising but in phase 3 randomized controlled trials resulted in disappointing results compared to systemic chemotherapy. More recent work however, have shown that increasing the radiation dose to the tumor to at least 60Gy and combining with more effective systemic therapies are starting to produce better clinical results. There have also been advances in the angiographic methods used to make this into a day-case technique and the use of new radionuclides such as Ho-166 and Re-188 provides a wider range of possible SIRT techniques.