Search Results (48)

Background: Meta-analyses on the prevalence and significance of thyroid incidentalomas at PET (TIP) are available only about [¹⁸F]FDG. Focal TIP at [¹⁸F]FDG PET is not rare and may be malignant lesions in about one-third of cases. The aim of this study is to perform a meta-analysis on the prevalence and clinical significance of TIP using other PET radiotracers beyond [¹⁸F]FDG. Methods: A comprehensive literature search of studies about TIP was carried out using four different databases, screened until 31 December 2024. Only original articles about TIP using radiopharmaceuticals other than [¹⁸F]FDG were selected. A proportion meta-analysis on the prevalence and clinical significance of TIP was carried out on a patient-based analysis using a random-effects model. Results: 21 studies (29,409 patients) were included in the meta-analysis. PET was performed using radiolabeled somatostatin analogues (SSA) [n = 5], choline [n = 6], prostate-specific membrane antigen (PSMA) [n = 7], or fibroblast activation protein inhibitors (FAPI) [n = 3]. The uptake pattern of TIP was described as focal, diffuse, or mixed/heterogeneous. The pooled prevalence of TIP was 5.6% for SSA-PET, 6.1% for choline-PET, 4.2% for PSMA-PET, and 3.6% for FAPI-PET. The final diagnosis of TIP with a diffuse pattern was a benign condition or represented a physiological uptake. Conversely, TIP with focal or mixed/heterogeneous pattern may represent a benign condition in most cases, but even a malignant lesion in 6–10% of cases. Conclusions: As for [¹⁸F]FDG, TIP using other radiopharmaceuticals is not rare. Most of them are benign, but those with focal or heterogeneous uptake patterns may represent a malignant lesion in some cases (even if the risk of malignancy is lower compared to [¹⁸F]FDG PET), thus requiring further evaluation. Further studies are warranted to better clarify the clinical impact of TIP detection. Full article

Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances in molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and the PI3K/AKT/mTOR pathway are critical drivers of disease progression and therapeutic resistance. Despite the established benefits of hormone therapy, chemotherapy, and bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs have highlighted the importance of identifying actionable genetic alterations, such as BRCA2 or ATM defects, that render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts have refined imaging—particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography—to detect and localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable the real-time tracking of emergent AR splice variants or reversion mutations, supporting adaptive therapy paradigms. Nonetheless, the complexity of mPCa necessitates combination strategies, such as pairing AR inhibition with PI3K/AKT blockade or PARP inhibitors, to inhibit tumor plasticity. Immuno-oncological approaches remain challenging for unselected patients; however, subsets with mismatch repair deficiency or neuroendocrine phenotypes may benefit from immune checkpoint blockade or targeted epigenetic interventions. We present these pivotal advances, and discuss how biomarker-guided integrative treatments can improve mPCa management. Full article

Prostate cancer ranks as the fourth most common cancer among men, with approximately 1.47 million new cases reported annually. The emergence of prostate-specific membrane antigen (PSMA) as a critical biomarker has revolutionized the diagnosis and treatment of prostate cancer. Recent advancements in low-molecular-weight PSMA inhibitors, with their diverse chemical structures and binding properties, have opened new avenues for research and therapeutic applications in prostate cancer management. These novel agents exhibit enhanced tumor targeting and specificity due to their small size, facilitating rapid uptake and localization at the target site while minimizing the retention in non-target tissues. The primary aim of this study is to evaluate the potential of low-molecular-weight PSMA inhibitors labeled with radioisotopes as theranostic agents for prostate cancer. This includes assessing their efficacy in targeted imaging and therapy and understanding their pharmacokinetic properties and mechanisms of action. This study is a literature review focusing on in vitro and clinical research data. The in vitro studies utilize PSMA-targeted radioligands labeled with radioisotopes to assess their binding affinity, specificity, and internalization in prostate cancer cell lines. Additionally, the clinical studies evaluate the safety, effectiveness, and biodistribution of radiolabeled PSMA ligands in patients with advanced prostate cancer. The findings indicate promising outcomes regarding the safety and efficacy of PSMA-targeted radiopharmaceuticals in clinical settings. The specific accumulation of these agents in prostate tumor lesions suggests their potential for various applications, including imaging and therapy. This research underscores the promise of radiopharmaceuticals targeting PSMA in advancing the diagnosis and treatment of prostate cancer. These agents improve diagnostic accuracy and patients’ outcomes by enhancing imaging capabilities and enabling personalized treatment strategies. Full article

The Prostate cancer (PC) is a major problem all over worldwide and this is the second highest cancer-related mortality rate after lung cancer all over worldwide. At least 299,010 likely cases in men were reported in the US in 2024 and about 35,250 deaths are reported. The overexpression of prostate-specific membrane antigen (PSMA) is a key factor in the progression of prostate cancer and contributes to metastasis in lymph nodes, soft tissues and bones metastasis. The numerous studies have reported that, Glu-ureido-based molecules exhibit high binding affinity for PSMA. The earliest imaging agents developed from this structure were labeled with radioactive halogen isotopes and demonstrated nanomolar binding affinity, leading to exceptional imaging properties. Hence the Glu-ureido chemical moiety is a very important template as inhibitor of PSMA. In this study to explore the chemical structural and electronic features of Glu-Ureido structure with the aid of quantum chemistry computer simulations. In this study, first optimized the structure of this chemical structure using the B3LYP 6311-G (++, d, p) basis set. In this study investigated the maximal quantity of electronic charge transfer (N_max), chemical hardness (η), electrostatic potential, chemical potential (µ) and electrophilicity (ω). By the using Natural Bond Orbital (NBO) analysis, the examination shows that the molecule’s chemically active regions π-electron-electron delocalization within the molecule that contribute to its stability. Full article

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, was shown to be expressed 100–1000 fold higher in prostate adenocarcinoma as compared to normal prostate epithelium. Given the enzymatic function of PSMA with the presence of an internalization triggering motif, various Glu-urea-Lys-based inhibitors have been developed and, amongst others, radiolabeled with positron emitters for targeted positron emission tomography imaging such as ⁶⁸Ga-PSMA-HBED-CC Glu-urea-Lys(Ahx) as well as with beta and alpha-emitting radioisotopes for targeted therapy, e.g., ¹⁷⁷Lu-PSMA-617. In this paper, we review and discuss the potential implications for targeted imaging and therapy of altered PSMA-glycosylation, of PSMA-driven activation of the P13K/Akt/mTOR, of the evolution over time and the relationship with androgen signaling and changes in DNA methylation of PSMA, and of androgen deprivation therapy (ADT) in prostate carcinoma. Full article

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. ¹⁸F-FDG PET/CT has been widely used and has demonstrated prognostic value, but ¹⁸F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice. Full article

Prostate cancer is the most prevalent cancer among men in the United States and is a leading cause of cancer-related death. Prostate specific membrane antigen (PSMA) has been established as a biomarker for prostate cancer diagnosis and treatment. This study aimed to develop a novel theranostic agent, PSMA-1-MMAE-Pc413, which integrates a PSMA-targeting ligand, the photosensitizer Pc413, and the microtubular inhibitor monomethyl auristatin E (MMAE) for synergistic therapeutic efficacy. In vitro uptake studies revealed that PSMA-1-MMAE-Pc413 demonstrated selective and specific uptake in PSMA-positive PC3pip cells but not in PSMA-negative PC3flu cells, with the uptake in PC3pip cells being approximately three times higher. In vitro cytotoxicity assays showed that, when exposed to light, PSMA-1-MMAE-Pc413 had a synergistic effect, leading to significantly greater cytotoxicity in PSMA-positive cells (IC₅₀ = 2.2 nM) compared to PSMA-1-Pc413 with light irradiation (IC₅₀ = 164.9 nM) or PSMA-1-MMAE-Pc413 without light irradiation (IC₅₀ = 12.6 nM). In vivo imaging studies further demonstrated the selective uptake of PSMA-1-MMAE-Pc413 in PC3pip tumors. In in vivo studies, PSMA-1-MMAE-Pc413 dramatically improves the therapeutic outcome for prostate cancer by providing a synergistic effect that surpasses the efficacy of each treatment modality alone in PC3pip tumors. These findings suggest that PSMA-1-MMAE-Pc413 has strong potential for clinical application in improving prostate cancer treatment. Full article

This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer—mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate. Full article

Thyroid cancer poses a significant challenge in clinical management, necessitating precise diagnostic tools and treatment strategies for optimal patient outcomes. This review explores the evolving field of radiotracers in the diagnosis and management of thyroid cancer, focusing on prostate-specific membrane antigen (PSMA)-based radiotracers, fibroblast activation protein inhibitor (FAPI)-based radiotracers, Arg-Gly-Asp (RGD)-based radiotracers, and ¹⁸F-tetrafluoroborate (¹⁸F-TFB). PSMA-based radiotracers, initially developed for prostate cancer imaging, have shown promise in detecting thyroid cancer lesions; however, their detection rate is lower than ¹⁸F-FDG PET/CT. FAPI-based radiotracers, targeting fibroblast activation protein highly expressed in tumors, offer potential in the detection of lymph nodes and radioiodine-resistant metastases. RGD-based radiotracers, binding to integrin αvβ3 found on tumor cells and angiogenic blood vessels, demonstrate diagnostic accuracy in detecting radioiodine-resistant thyroid cancer metastases. ¹⁸F-TFB emerges as a promising PET tracer for imaging of lymph node metastases and recurrent DTC, offering advantages over traditional methods. Overall, these radiotracers show promise in enhancing diagnostic accuracy, patient stratification, and treatment selection in differentiated thyroid cancer, warranting further research and clinical validation. Given the promising staging capabilities of 18F-TFB and the efficacy of FAP-targeting tracers in advanced, potentially dedifferentiated cases, continued investigation in these domains is justified. Full article

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (¹⁷⁷Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of ¹⁷⁷Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of ¹⁷⁷Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of ¹⁷⁷Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies. Full article

Prostate cancer accounts for a significant proportion of cancer diagnoses in Canadian men. Over the past decade, the therapeutic landscape for the management of metastatic prostate cancer has undergone rapid changes. Novel strategies use hormonal agents, chemotherapy, homologous recombination repair inhibitors, and radioligand therapy or combination strategies in addition to androgen deprivation therapy. In this review, we summarize the available data addressing key therapeutic areas along the disease continuum and focus on practical aspects for general practitioners in oncology managing patients with metastatic prostate cancer. Full article

Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [^99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [^99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [^99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [^99mTc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [^99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [^99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT). Full article

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide including two phenylalanine residues in the L-configuration as the peptide fragment of the linker, and 3- or 4-(tributylstannyl)benzoic acid as a prosthetic group in their structures for radiolabeling. The standard compounds [¹²⁷I]PSMA-m-IB and [¹²⁷I]PSMA-p-IB for comparative and characterization studies were first synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach, in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence followed by replacement of the Sn(Bu)₃ group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [¹²³I]PSMA-p-IB was higher than that of [¹²³I]PSMA-m-IB, which were 74.9 ± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [¹²³I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [¹²³I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [¹²³I]PSMA-p-IB showed less accumulation than [¹⁷⁷Lu]Lu-PSMA-617 in several normal organs (liver, kidney, and bone). These results warrant further preclinical development, including toxicology evaluation and experiments in tumor-bearing mice. Full article

Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC. Full article

Prostate cancer is the second most common cancer among men. We designed and synthesized new ligands targeting prostate-specific membrane antigen and suitable for bimodal conjugates with diagnostic and therapeutic agents. In vitro studies of the affinity of the synthesized compounds to the protein target have been carried out. Based on these ligands, a series of bimodal conjugates with a combination of different mitosis inhibitors and antiandrogenic drugs were synthesized. The cytotoxicity of the compounds obtained in vitro was investigated on three different cell lines. The efficacy of the two obtained conjugates was evaluated in vivo in xenograft models of prostate cancer. These compounds have been shown to be highly effective in inhibiting the growth of PSMA-expressing tumors. Full article