Predictive and prognostic potential of pretreatment 68Ga-PSMA PET tumor heterogeneity index in patients with metastatic castration-resistant prostate cancer treated with 177Lu-PSMA.

Introduction: This study was conducted to evaluate the predictive values of volumetric parameters and radiomic features (RFs) extracted from pretreatment 68Ga-PSMA PET and baseline clinical parameters in response to 177Lu-PSMA therapy. Materials and methods: In this retrospective multicenter study, mCRPC patients undergoing 177Lu-PSMA therapy were enrolled. According to the outcome of therapy, the patients were classified into two groups including positive biochemical response (BCR) (≥ 50% reduction in the serum PSA value) and negative BCR (< 50%). Sixty-five RFs, eight volumetric parameters, and also seventeen clinical parameters were evaluated for the prediction of BCR. In addition, the impact of such parameters on overall survival (OS) was evaluated. Results: 33 prostate cancer patients with a median age of 69 years (range: 49-89) were enrolled. BCR was observed in 22 cases (66%), and 16 cases (48.5%) died during the follow-up time. The results of Spearman correlation test indicated a significant relationship between BCR and treatment cycle, administered dose, HISTO energy, GLCM entropy, and GLZLM LZLGE (p<0.05). In addition, according to the Mann-Whitney U test, age, cycle, dose, GLCM entropy, and GLZLM LZLGE were significantly different between BCR and non BCR patients (p<0.05). According to the ROC curve analysis for feature selection for prediction of BCR, GLCM entropy, age, treatment cycle, and administered dose showed acceptable results (p<0.05). According to SVM for assessing the best model for prediction of response to therapy, GLCM entropy alone showed the highest predictive performance in treatment planning. For the entire cohort, the Kaplan-Meier test revealed a median OS of 21 months (95% CI: 12.12-29.88). The median OS was estimated at 26 months (95% CI: 17.43-34.56) for BCR patients and 13 months (95% CI: 9.18-16.81) for non BCR patients. Among all variables included in the Kaplan Meier, the only response to therapy was statistically significant (p=0.01). Conclusion: This exploratory study showed that the heterogeneity parameter of pretreatment 68Ga-PSMA PET images might be a potential predictive value for response to 177Lu-PSMA therapy in mCRPC; however, further prospective studies need to be carried out to verify these findings.

Peptide Receptor Radionuclide Therapy Using 177 Lu-DOTATATE in Advanced Neuroendocrine Tumors (NETs) in a Limited-Resource Environment.

Background This study was conducted to evaluate the clinical efficacy and safety of peptide receptor radionuclide therapy (PRRT) using 177 Lu-DOTA0-Tyr3-octreotate (DOTATATE) in patients with neuroendocrine tumors (NETs). Methods Sixteen patients with pathologically verified NETs including eight females and eight males were enrolled in this study. Before PRRT, the patients underwent 68 Ga-DOTATATE positron emission tomography/computed tomography or 99m Tc-octreotide scintigraphy for evaluation of somatostatin receptor expression. Response to treatment was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). In addition, for evaluation of toxicity, monthly blood analysis was performed including hematology, renal function (creatinine) test, and liver function test. The Eastern Cooperative Oncology Group (ECOG) status performance was applied to estimate the patients' general condition in a scale of 0 (fully active) to 5 (dead). In addition, overall survival (OS) was calculated as the time interval from the start of PRRT to death from any reason. Results Sixteen patients including eight females and eight males with a median age of 60.5 years (range: 24-74) were enrolled in this study. The patients underwent PRRT with a median cycle of 3.5 (range: 1-7) and a median dose of 20.35 (range: 7.4-49.95 GBq). At the end of data collection, PR, CR, SD, and PD were seen in 11, 2, 1, and 2 patients according to the RECIST, respectively. Three patients expired during or after the PRRT period. The median ECOG and Karnofsky Performance Scale was 1.5 and 75 before PRRT, which improved significantly to 1 and 80 after PRRT, respectively ( p < 0.05). According to the Kaplan-Meier test, the median OS was 23 months (95% confidence interval: 7.90-38.09). According to the National Cancer Institute's Common Terminology Criteria for Adverse Events, three patients showed grade I and three patients showed grade II leucopenia. Furthermore, three and seven patients had grade II and grade I anemia, respectively. Conclusion Since PRRT using 177 Lu-DOTATATE has a favorable response rate and few adverse effects and improves the quality of life in NETs, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.

Comparison of 18 F-NaF Imaging, 99m Tc-MDP Scintigraphy, and 18 F-FDG for Detecting Bone Metastases.

Bone is a common metastasis site in several malignancies, most importantly prostate and breast cancers. Given the significance of the early and accurate diagnosis of bone metastases for preliminary staging, treatment planning and monitoring, restaging, and survival prediction in patients with malignancy, it is critical to compare and contrast the strengths and weaknesses of imaging modalities. Although technetium-99m-labeled diphosphonates [ 99m Tc-MDP] scintigraphy has been used for assessing skeletal involvement, there is a renewed interest in fluorine-18-labeled sodium fluoride [ 18 F-NaF] bone imaging with positron emission tomography or positron emission tomography/computed tomography, since this approach provides essential advantages in bone metastases evaluation. This review study aimed to discuss the basic and technical aspects of 18 F-NaF imaging and its mechanism of action, and compare this modality with the 99m Tc-MDP bone scan and 18F-fluorodeoxyglucose using current evidence from the pertinent literature and case examples of the center in the study.

Multimodal assessment of regional gray matter integrity in early relapsing-remitting multiple sclerosis patients with normal cognition: a voxel-based structural and perfusion approach.

OBJECTIVE: There is increasing evidence that gray matter (GM) impairment is strongly associated with clinical performance decline. We aim to perform a voxelwise analysis between regional GM (rGM) perfusion and structural abnormalities in early relapsing-remitting multiple sclerosis patients with normal cognition (RRMS-IC) and explore clinical correlate of early rGM abnormalities. METHODS AND MATERIALS: We studied 14 early RRMS-IC patients and 14 healthy age- and sex-matched controls. Brain perfusion single photon emission computed tomography (SPECT), structural MRI, and a comprehensive neuropsychological examination were acquired from all participants. Neuropsychological tests include expanded disability status scale, minimal mental status examination, short physical performance battery, Wechsler memory scale, and quick smell test. Voxel-based morphometry was used for analyzing SPECT and T1-MR images to identify rGM hypoperfusion and atrophy, respectively (RRMS-IC vs controls (group analysis), and also, each patient vs controls (individual analysis)) (p < 0.001). Then, anatomical location of impaired regions was acquired by automated anatomical labeling software. RESULTS: There was no significant difference in total GM volume between RRMS-IC and healthy controls, however, rGM atrophy and hypoperfusion were detected. Individual analysis revealed more rGM impairment compared with group analysis. rGM hypoperfusion was more extensive rather than rGM atrophy in RRMS-IC. There was no spatial association between rGM atrophy and rGM hypoperfusion (p > 0.05). rGM abnormalities correlated with several relevant minimal clinical deficits. CONCLUSION: Lack of spatial correlation between rGM atrophy and hypoperfusion might suggest that independent mechanisms might underlie atrophy and hypoperfusion. Perfusion SPECT may provide supplementary information along with MRI. ADVANCES IN KNOWLEDGE: Association between rGM atrophy and rGM hypoperfusion and their clinical significance in early RRMS-IC is not well described yet. Our study showed that there is spatial dissociation between rGM atrophy and rGM hypoperfusion, suggesting that different mechanisms might underlie these pathologies.

State-of-the-art modalities in cardio-oncology: insight from a nuclear medicine approach.

Cancer and cardiovascular disease are the most significant causes of morbidity and mortality worldwide. Although the cancer survival rate has increased due to improved treatment approaches, especially targeted therapy, some side effects such as cardiotoxicity decrease the efficiency of the clinical outcome. Radiation therapy and chemotherapy have a long-established history of potential cardiotoxic effects. A new multi-disciplinary and translational field known as cardio-oncology has been developed for the identification, prevention, and treatment of cardiovascular dysfunctions associated with cancer treatment approaches. One of the important tools for detecting and monitoring cardiotoxic effects is non-invasive nuclear cardiac imaging techniques. Cardiac nuclear imaging modalities especially recent findings positron emission tomography (PET) tracers have a quintessential role in the early detection of cardiovascular disorders. Moreover, comprehensive studies are required to investigate novel nuclear medicine treatment approaches such as peptide receptor radionuclide therapy (PRRT), fibroblast activation protein (FAP), and chemokine receptor (CXCR) targeting probes for possible cardiac side effects that play important roles in the treatment of malignancies.

Feasibility and Therapeutic Potential of 177Lu-Fibroblast Activation Protein Inhibitor-46 for Patients With Relapsed or Refractory Cancers: A Preliminary Study.

INTRODUCTION: Fibroblast activation protein (FAP) is a member of the serine protease family and has a high expression in the stroma of approximately 90% of epithelial malignancies. The present investigation aimed to assess the feasibility, safety, and dosimetry data of 177Lu-FAPI-46 in diverse malignancies. PATIENTS AND METHODS: Patients with advanced cancers with nonoperable tumors, or tumors refractory to conventional therapies, were enrolled. Treatment included escalating doses of 177Lu-FAPI-46 (1.85-4.44 GBq) per cycle using a combination of clinical and statistical expertise design, and intervals of 4 to 6 weeks were considered between the cycles. Biodistribution and dosimetry were examined by whole-body scans. We applied the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 to measure peptide-targeted radionuclide therapy (PTRT)-associated toxicity. RESULTS: A total of 21 patients (11 females and 10 males) with a median age of 50 years (range, 6-79 years) were investigated. Of 21 participants, 18 cases were selected for PTRT. Overall, 36 PTRT cycles were performed. The median number of PTRT cycles and the median injected amount of activity in each cycle were 2 and 3.7 GBq, respectively. The dosimetric analysis revealed median absorbed doses of 0.026, 0.136, 0.886, and 0.02 with ranges of 0.023-0.034, 0.001-0.2, 0.076-1.39, and 0.002-0.2 mGy/MBq for the whole body, liver, kidneys, and spleen, respectively. The therapy was well tolerated in almost all patients. CONCLUSIONS: The findings of this preliminary investigation might indicate the potential feasibility and safety of PTRT using 177Lu-FAPI-46 for different aggressive tumors. Moreover, the current study could be beneficial in determining the suitable amount of activity for a phase 2 study.

Theranostic Approach in Breast Cancer: A Treasured Tailor for Future Oncology.

ABSTRACT: Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades. One of the intensively developing fields is nuclear medicine combining molecular diagnostic imaging and subsequent (radio)therapy in the light of theranostics. This review aimed to survey the current status of preclinical and clinical research using theranostic approach in breast cancer patients with potential to translate into conventional treatment strategies alone or in combination with other common treatments, especially in aggressive and resistant types of breast cancer. In addition, we present 5 patients with breast cancer who were refractory or relapsed after conventional therapy while presumably responded to the molecular radiotherapy with 177Lu-trastuzumab (Herceptin), 177Lu-DOTATATE, and 177Lu-FAPI-46.

Theranostics in Brain Tumors.

Theranostic nuclear oncology, mainly in neuro-oncology (neurotheranostics), aims to combine cancer imaging and therapy using the same targeting molecule. This approach tries to identify patients who are most likely to benefit from tumor molecular radionuclide therapy. The ability of radioneurotheranostic agents to interact with cancer cells at the molecular level with high specificity can significantly improve the effectiveness of cancer therapy. A variety of biologic targets are under investigation for treating brain tumors. PET-based precision imaging can substantially improve the therapeutic efficacy of radiotheranostic approach in brain tumors.

Emerging Preclinical and Clinical Applications of Theranostics for Nononcological Disorders.

Studies in nuclear medicine have shed light on molecular imaging and therapeutic approaches for oncological and nononcological conditions. Using the same radiopharmaceuticals for diagnosis and therapeutics of malignancies, the theranostics approach, has improved clinical management of patients. Theranostic approaches for nononcological conditions are recognized as emerging topics of research. This review focuses on preclinical and clinical studies of nononcological disorders that include theranostic strategies. Theranostic approaches are demonstrated as possible in the clinical management of infections and inflammations. There is an emerging need for randomized trials to specify the factors affecting validity and efficacy of theranostic approaches in nononcological diseases.

A Path to New Normal of Nuclear Medicine Facilities: Considerations for Reopening.

The stormy clouds of the coronavirus disease 2019 outbreak caused a rapidly spreading epidemic still hanging over the sphere. Any steps to transition toward a new normal should be guided by health authorities, together with economic and societal considerations. There are various items mainly falling into three classifications, including patient worry, clinical demand, and economic recession. Social distancing, lay-offs, and decreased number of patients with health insurance may lead to a prolonged period to retrieve normalcy. To return to a new normal, an individualized management model should be developed for each laboratory based on staff, instruments, services, crowding, physical space, hospital base unit, or outpatient clinic. Continuous training of different occupational staffs is among the key parameters in maintaining this readiness. The proposed response model should have internal and systemic integrity as well as coherence among the included items in two intra- and inter-unit management categories, namely thinking globally and acting locally.

Precision Medicine Approach in Prostate Cancer.

Prostate cancer is the most prevalent type of cancer and the second cause of death in men worldwide. Various diagnostic and treatment procedures are available for this type of malignancy, but High-grade or locally advanced prostate cancers showed the potential to develop to lethal phase that can be causing dead. Therefore, new approaches are needed to prolong patients' survival and to improve their quality of life. Precision medicine is a novel emerging field that plays an essential role in identifying new sub-classifications of diseases and in providing guidance in treatment that is based on individual multi-omics data. Multi-omics approaches include the use of genomics, transcriptomics, proteomics, metabolomics, epigenomics and phenomics data to unravel the complexity of a disease-associated biological network, to predict prognostic biomarkers, and to identify new targeted drugs for individual cancer patients. We review the impact of multi-omics data in the framework of systems biology in the era of precision medicine, emphasising the combination of molecular imaging modalities with highthroughput techniques and the new treatments that target metabolic pathways involved in prostate cancer.

Bench-to-Bedside Theranostics in Nuclear Medicine.

The optimum selection of the appropriate radiolabelled probe for the right target and the right patient is the foundation of theranostics in personalised medicine. In nuclear medicine, this process is realised through the appropriate choice of radiopharmaceuticals based on molecular biomarkers regarding molecular imaging. Theranostics is developing a strategy that can be used to implement accepted tools for individual molecular targeting, including diagnostics, and advances in genomic molecular knowledge, which has led to identifying theranostics biomaterials that have the potency to diagnose and treat malignancies. Today, numerous studies have reported on the discovery and execution of these radiotracers in personalised medicine. In this review, we presented our point of view of the most important theranostics agents that can be used to treat several types of malignancies. Molecular targeted radionuclide treatment methods based on theranostics are excellent paradigms of the relationship between molecular imaging and therapy that has been used to provide individualised or personalised patient care. Toward that end, a precise planned prospective examination of theranostics must be done to compare this approach to more standard therapies.

Radioimmunotherapy (RIT) in Brain Tumors.

Annually, the incidence of brain tumors has slightly increased and also the patient prognosis is still disappointing, especially for high-grade neoplasms. So, researchers seek methods to improve therapeutic index as a critical aim of treatment. One of these new challenging methods is radioimmunotherapy (RIT) that involves recruiting a coupling of radionuclide component with monoclonal antibody (mAb) which are targeted against cell surface tumor-related antigens or antigens of cells within the tumor microenvironment. In the context of cancer care, precision medicine is exemplified by RIT; precision medicine can offer a tailored treatment to meet the needs for treatment of brain tumors. This review aims to discuss the molecular targets used in radioimmunotherapy of brain tumors, available and future radioimmunopharmaceutics, clinical trials of radioimmunotherapy in brain neoplasms, and eventually, conclusion and future perspective of application of radioimmunotherapy in neurooncology cancer care.

Advanced modalities of molecular imaging in precision medicine for musculoskeletal malignancies.

Musculoskeletal malignancies consist of a heterogenous group of mesenchymal tumors, often with high inter- and intratumoral heterogeneity. The early and accurate diagnosis of these malignancies can have a substantial impact on optimal treatment and quality of life for these patients. Several new applications and techniques have emerged in molecular imaging, including advances in multimodality imaging, the development of novel radiotracers, and advances in image analysis with radiomics and artificial intelligence. This review highlights the recent advances in molecular imaging modalities and the role of non-invasive imaging in evaluating tumor biology in the era of precision medicine.