RESUMO
Advancements in somatostatin receptor (SSTR) targeted imaging and treatment of well-differentiated neuroendocrine tumors (NETs) have revolutionized the management of these tumors. This comprehensive review delves into the current practice, discussing the use of the various FDA-approved SSTR-agonist PET tracers and the predictive imaging biomarkers, and elaborating on Lu177-DOTATATE peptide receptor radionuclide therapy (PRRT) including the evolving areas of post-therapy imaging practices, PRRT retreatment, and the potential role of dosimetry in optimizing patient treatments. The future directions sections highlight ongoing research on investigational PET imaging radiotracers, future prospects in alpha particle therapy, and combination therapy strategies.
Assuntos
Tumores Neuroendócrinos , Compostos Radiofarmacêuticos , Receptores de Somatostatina , Humanos , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Receptores de Somatostatina/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendências , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêuticoRESUMO
Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [177Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [177Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (ΔTBS) and changes in normalized peak count (ΔnPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ΔTBSsecond-first, ΔTBSthird-first, and ΔTBSfourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [177Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. -0.049, 0.08 vs. -0.116, and 0.109 vs. -0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). ΔnPCsecond-first showed significant group differences (mean, -0.107 vs. -0.282; P = 0.033); ΔnPCthird-first and ΔnPCfourth-first did not reach statistical significance (mean, -0.122 vs. -0.312 and -0.183 vs. -0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, ΔTBSfourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ΔTBSsecond-first and ΔTBSthird-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ΔnPCsecond-first, ΔnPCthird-first, and ΔnPCfourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: ΔTBS and ΔnPC can predict [177Lu]Lu-DOTATATE response by the second treatment session.
Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Octreotida , Compostos Organometálicos , Neoplasias Pancreáticas , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Compostos Organometálicos/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Intestinais/radioterapia , Neoplasias Intestinais/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/radioterapia , Resultado do Tratamento , Adulto , Idoso de 80 Anos ou maisRESUMO
The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [177Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, advanced, well-differentiated G1 and G2 in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) treated with [177Lu]Lu-DOTA-TATE according to the decisions of a multidisciplinary team. All patients underwent four cycles of 7-8 GBq of [177Lu]Lu-DOTA-TATE every 8 weeks. A whole-body scan (WBS) was performed 4, 48, and 168 h after each treatment. The dosimetry towards the organ at risk and target lesions was calculated. For each patient, renal and bone marrow parameters were evaluated before, during, and 3 months after the end of the treatment. Follow-up data were obtained and RECIST criteria were considered as the endpoint. Among 21 patients enrolled (mean age 65 ± 9 years); 17 (81%) were men and the small intestine was the most frequent location of disease (n = 12). A mild albeit significant variation (p < 0.05) in both platelets and white blood cell counts among all time points was observed, despite it disappearing 3 months after the end of the therapy. According to the RECIST criteria, 11 (55%) patients had a partial response to therapy and 8 (40%) had stable disease. Only one (5%) patient had disease progression 4 months after treatment. Our data confirm that [177Lu]Lu-DOTA is safe and effective in controlling the burden disease of G1/G2 GEP-NETs patients.
Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Octreotida , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/radioterapia , Masculino , Feminino , Idoso , Neoplasias Pancreáticas/radioterapia , Pessoa de Meia-Idade , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Neoplasias Intestinais/radioterapia , Neoplasias Gástricas/radioterapia , Compostos Organometálicos/uso terapêutico , Receptores de Peptídeos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Neuroendocrine tumours (NETs) are a heterogeneous group of tumours, which is characterized by rich vascularization. The role of angiogenesis in NETs has been widely researched. Peptide receptor radionuclide therapy (PRRT) is an effective treatment method for patients with disease progression in NETs. Due to the heterogeneousness of NETs, the response to treatment varies. Currently, the finding of efficient markers helpful in assessing the response to treatment in NETs is crucial. The aim of this study was to assess chromogranin A (CgA) and angiogenic factors in gastro-entero-pancreatic (GEP) and broncho-pulmonary (BP) NET patients treated with PRRT. MATERIAL AND METHODS: The study group included 40 patients with GEP NETs and BP NETs who completed four cycles of PRRT. Serum levels of CgA and angiogenic factors such as vascular endothelial growth factor (VEGF), its receptors (VEGF-R1, VEGF-R2, VEGF-R3), were assessed before and after four cycles of PRRT. All tests were determined using ELISA. RESULTS: The concentration of CgA, VEGF-R1 and VEGF-R2 decreased significantly, whereas VEGF-R3 increased significantly after PRRT. PRRT did not affect VEGF, it was similar before and after the radioisotope treatment. Based on AUROC, only for VEGF-R1 AUC was a consequence of 0.7 which can be considered as a good response to PRRT treatment. CONCLUSIONS: VEGF-R1 may be a potential biomarker useful in assessing the effectiveness of PRRT in NET patients.
Assuntos
Cromogranina A , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Cromogranina A/sangue , Receptores de Peptídeos/metabolismo , Biomarcadores Tumorais/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Neovascularização Patológica/radioterapia , Neovascularização Patológica/sangue , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/sangue , Resultado do TratamentoRESUMO
Proper collimator selection is critical to obtaining high-quality, interpretable nuclear medicine images. Collimators help eliminate scatter, which leads to poor spatial resolution and blurry images. We present the case of a posttherapy 177Lu-DOTATATE (Lutathera) patient who was initially imaged with a low-energy, high-resolution collimator routinely used in 99mTc imaging. On image review, the patient was reimaged with the appropriate medium-energy, high-resolution collimator, which resulted in improved image quality. When reviewing the quality of images, it is important to understand modifications to the imaging that can significantly improve image quality and interpretation.
Assuntos
Octreotida , Compostos Organometálicos , Humanos , Octreotida/análogos & derivados , Octreotida/uso terapêuticoRESUMO
Glucagonoma is a rare pancreatic neuroendocrine tumor (panNET) that can be characterized by increased secretion of glucagon and distinguishing symptoms - glucagonoma syndrome with a typical dermatosis, necrolytic migratory erythema, being its most common manifestation. While surgery and somatostatin analogs remain first-line therapeutic options in panNETs, radioligand therapy with [177Lu]Lu-DOTA-TATE is a recommended second-line palliative treatment in advanced, metastatic cases. However, its prospects and efficacy are still not vastly researched in less frequent neuroendocrine neoplasms. Here, we present an extraordinary case of a metastatic glucagonoma treated with [177Lu]Lu-DOTA-TATE used as a second-line treatment in progressive disease.
Assuntos
Glucagonoma , Octreotida , Compostos Organometálicos , Neoplasias Pancreáticas , Humanos , Glucagonoma/diagnóstico por imagem , Compostos Organometálicos/uso terapêutico , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/patologia , Metástase Neoplásica , Masculino , Pessoa de Meia-IdadeAssuntos
Terapia Neoadjuvante , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/terapia , Terapia Neoadjuvante/métodos , Octreotida/uso terapêutico , Octreotida/análogos & derivados , Receptores de Peptídeos/metabolismo , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
AIMS: This study aimed to evaluate the effectiveness of somatostatin analogues (SA) for cystoid maculopathy (CM) in retinitis pigmentosa (RP) patients. MATERIALS AND METHODS: In this retrospective case series, clinical and imaging characteristics of 28 RP patients with CM, unresponsive to carbonic anhydrase inhibitors, were collected from medical charts. All patients received SA treatment as an alternative (octreotide long-acting release at 20 mg/month or 30 mg/month, or lanreotide at 90 mg/month or 120 mg/month). Outcome measures were mean reduction in foveal thickness (FT) and foveal volume (FV) and mean increase in best-corrected visual acuity at 3, 6 and 12 months of treatment initiation. Linear mixed models were used to calculate the effectiveness over time. RESULTS: 52 eyes of 28 RP patients were included; 39% were male. The median age at the start of treatment was 39 years (IQR 30-53). Median follow-up was 12 months (range 6-12). From baseline to 12 months, the mean FT decreased from 409±136 µm to 334±119 µm and the mean FV decreased from 0.31±0.10 mm3 to 0.25±0.04 mm3. Linear mixed model analyses showed a significant decrease in log FT and log FV at 3, 6 and 12 months after the start of treatment compared with baseline measurements (p<0.001, p<0.001, p<0.001). Mean best-corrected visual acuity did not increase significantly (0.46±0.35 logMAR to 0.45±0.38 logMAR after 12 months). DISCUSSION: SA may be an effective alternative treatment to reduce CM in RP patients.
Assuntos
Retinose Pigmentar , Somatostatina , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Retinose Pigmentar/tratamento farmacológico , Masculino , Feminino , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Estudos Retrospectivos , Pessoa de Meia-Idade , Acuidade Visual/efeitos dos fármacos , Adulto , Peptídeos Cíclicos/uso terapêutico , Octreotida/uso terapêutico , Octreotida/administração & dosagem , Resultado do Tratamento , Edema Macular/tratamento farmacológico , Edema Macular/etiologiaRESUMO
Pituitary carcinoma is a rare entity comprising 0.1-0.2% of all pituitary tumors and presents significant diagnostic and therapeutic challenges. Intraspinal drop metastasis in these tumors is even rarer. We report a case of a prolactin secreting pituitary carcinoma with intracranial metastasis and multiple intraspinal drop metastasis. This is the first case where 68Gallium labelled [1,4,7,10 - tetraazacyclododecane - 1,4,7,10 - tetraacetic acid] -1- NaI3 - octreotide (68Ga-DOTANOC) whole-body positron emission tomography-computed tomography (PET-CT) has been used in a case of malignant prolactinoma, in an attempt to ascertain the somatostatin receptor (SSTR) expression on tumor cells. Through this paper, we suggest that SSTR targeted radionuclide therapy could have a potential role in aggressive pituitary tumors and pituitary carcinomas similar to the promising role of lutetium-labelled peptides in inoperable or metastasized gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).
Assuntos
Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , Prolactinoma/diagnóstico por imagem , Prolactinoma/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Adulto , Compostos Organometálicos/uso terapêutico , Prolactina/metabolismo , Feminino , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Pessoa de Meia-Idade , Receptores de Somatostatina/metabolismo , Octreotida/análogos & derivados , Octreotida/uso terapêuticoRESUMO
Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.
Assuntos
Everolimo , Metástase Neoplásica , Tumores Neuroendócrinos , Octreotida , Everolimo/uso terapêutico , Humanos , Masculino , Feminino , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/patologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Octreotida/efeitos adversos , Adulto , Receptores de Peptídeos/metabolismo , França , Compostos Organometálicos/uso terapêutico , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with 68Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with 90Y/177Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups. Methods: From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with 90Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with 177Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles. All patients showed intense uptake at diagnostic 68Ga-DOTATOC PET/CT or in an 111In-octreotide scan. Results: Of 42 patients treated, 5 patients received 90Y-DOTATOC with a cumulative activity of 11.1 GBq and 37 patients received 177Lu-DOTATATE with a cumulative activity of 22 GBq. The disease control rate was 57%. With a median follow-up of 63 mo, median progression-free survival was 16 mo, and median overall survival was 36 mo. Retreatment 177Lu-PRRT was performed in 6 patients with an administered median activity of 13 GBq in a mean of 5 cycles. With a 75.8-mo follow-up, median progression-free survival and overall survival were 6.5 and 17 mo, respectively. Only 1 patient discontinued the treatment because of grade 3 platelet toxicity. A rapidly transient grade 2 neutropenia was recorded in 1 retreated patient. Conclusion: PRRT in patients with advanced meningiomas overexpressing somatostatin receptor 2 was active and well tolerated, showing a 57% disease control rate. Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted.
Assuntos
Neoplasias Meníngeas , Meningioma , Octreotida , Humanos , Meningioma/radioterapia , Meningioma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Octreotida/efeitos adversos , Seguimentos , Adulto , Resultado do Tratamento , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/diagnóstico por imagem , Receptores de Peptídeos/metabolismo , Receptores de Somatostatina/metabolismo , Compostos Organometálicos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Neuroendocrine tumours (NETs) are a group of cancers that can produce hormones and other metabolically active compounds. The majority of NETs have specific tissue characteristics, such as the expression of somatostatin receptors (SSTR). Metabolic testing with [99mTc]Tc-EDDA/HYNIC-Tyr3-octreotide ([99mTc]Tc-EDDA/HYNIC-TOC) can be used in patients with NETs to visualize the presence of receptors in different locations of pathological lesions, including the skeletal system. The study aimed to calculate the body weight maximum standardized uptake value (SUVbwmax) of pathological bone lesions and healthy bone tissues, estimate the size of lesions, and identify a relationship between the SUVbwmax of the bone tissues, age and body mass of the study participants. MATERIAL AND METHODS: The somatostatin receptor scintigraphies (SRS) with [99mTc]Tc-EDDA/HYNIC-TOC were carried out at the Department of Nuclear Medicine, University Clinical Hospital No. 1, Pomeranian Medical University (PMU) in Szczecin from 2019 to 2022. Whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans were performed four hours after the injection of 700-800 MBq of [99mTc]Tc-EDDA/HYNIC-TOC in 344 patients with neuroendocrine tumours of various primary lesion locations. In 19 patients, who showed foci of increased radiopharmaceutical accumulation in bone location, the SUVbwmax was measured. The SUVbwmax of pathological bone lesions and healthy tissues were determined on SPECT/CT cross-sectional images using Xeleris 4 software. RESULTS: The total number of foci with increased SSTR expression in bone regions seen on scintigraphic images was 89. Among them, 32 bone lesions were visible on the corresponding CT scans. The mean SUVbwmax of these lesions was 31.39 [standard deviation (SD) 34.31]. For the other 57 lesions that were not visible on corresponding CT scans, the mean SUVbwmax was 19.12 (SD 24.24). The smallest bone lesion detected on the scintigram and visible on the corresponding CT location was 5 mm × 5 mm, measured in cross-section, and was located in the Th8 vertebral body; the largest, measuring 20 mm × 22 mm, was detected in the L3 vertebral body. The SUVbwmax of these lesions was 24.70 and 142.40, respectively. CONCLUSIONS: Bone lesions seen on SPECT/CT in [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy can be quantitatively analysed using the SUV index. Even a very small pathological bone lesion can be detected on [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy. It was shown that in cases where bone lesions were visible on CT scans, the SUVbwmax of bone tumour lesions was higher than when lesions were not visible on CT. Body mass does not affect the SUVbwmax of bone lesions. SUVbwmax of healthy bone tissue decreased with age.
Assuntos
Neoplasias Ósseas , Tumores Neuroendócrinos , Octreotida , Compostos de Organotecnécio , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Compostos de Organotecnécio/farmacocinética , Pessoa de Meia-Idade , Feminino , Masculino , Octreotida/análogos & derivados , Octreotida/farmacocinética , Adulto , Idoso , Transporte Biológico , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Cintilografia , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Well-differentiated neuroendocrine neoplasms (NETs) overexpress the somatostatin receptor, which is the target for the peptide receptor radionuclide therapy (PRRT). NETs have a slow growth rate and can metastasize to liver, bone, and lungs. In NETs patients, liver metastasis is an important prognostic marker because liver failure is one of the most common causes of death in this population. In this regard, we aimed to describe the changes in laboratorial parameters in patients submitted to PRRT with 177 Lu-DOTATATE, focusing on hepatic parameters. PATIENTS AND METHODS: One hundred ten patients treated with 1 to 4 cycles of 7.4 GBq (200 mCi) of 177 Lu-DOTATATE from January 2011 to December 2021 were analyzed in this retrospective observational single-center study. Patients were submitted to blood tests before and after each cycle of PRRT. Laboratory measurements were collected to assess liver function, cholestasis, kidney, and bone marrow function. RESULTS: In the general population (n = 110), ALP ( P = 0.013) and GGT ( P < 0.001) showed a statistically significant reduction. Patients with high liver disease volume showed a statistically significant reduction in ALT ( P = 0.016), whereas patients with low liver disease volume showed a statistically significant reduction in GGT ( P = 0.013). All parameters for bone marrow function showed a statistically significant decrease in all population subsets. CONCLUSIONS: Patients treated with 177 Lu-DOTATATE showed a significant improvement in liver function and cholestasis parameters, and a consistent decrease in bone marrow function, even in the presence of advanced liver disease.
Assuntos
Octreotida , Compostos Organometálicos , Humanos , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fígado/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Estudos de Coortes , Idoso de 80 Anos ou maisRESUMO
ABSTRACT: Glioblastoma multiforme (GBM) is a highly vascularized tumor with reported high prostate-specific membrane antigen (PSMA) expression. On the other hand, bevacizumab as an antiangiogenesis drug is increasingly used in the treatment of GBM recurrence. We present a case of GBM recurrence with significant reduction of 99m Tc-HYNIC-PSMA-11 uptake in her tumor 1 week after administration of 2 doses of bevacizumab with 2 weeks' interval. This case emphasizes the main mechanism of PSMA uptake in GBM secondary to angiogenesis and also implies a potential interaction of bevacizumab with PSMA uptake that should be especially considered during diagnostic and therapeutic application of PSMA radiotracers in GBM.
Assuntos
Bevacizumab , Glioblastoma , Compostos de Organotecnécio , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Feminino , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Recidiva , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Transporte Biológico , Pessoa de Meia-Idade , Ácido Edético/análogos & derivados , Radioisótopos de Gálio , Octreotida/análogos & derivadosRESUMO
BACKGROUND: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. METHODS: NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. RESULTS: From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. CONCLUSION: Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.
Surgical removal of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) can often cure patients. However, it is not known whether treating patients before surgery provides additional benefits. The main aim of the study was to investigate safety of treatment called peptide receptor radionuclide therapy with 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) before surgery in patients with NF-PanNETs. The NEOLUPANET study was conducted from March 2020 to February 2023 across multiple centres. Patients with NF-PanNETs that were at high risk of recurrence after surgery were included. All patients received 177Lu-DOTATATE before surgery. The main measure of success was safety, reflected by complications or death within 90 days after surgery. The study enrolled 31 patients and 26 completed four cycles of 177Lu-DOTATATE. Tumours shrank partially in 18 patients, and in 13 patients the tumour remained the same. No tumours increased in size. The entire tumour was removed in 28 of 29 patients. No patients died, but 72% had some complications (severe in 7 patients). The study found that using 177Lu-DOTATATE before surgery is safe and useful for treating patients with NF-PanNETs.
Assuntos
Terapia Neoadjuvante , Octreotida , Compostos Organometálicos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Octreotida/análogos & derivados , Idoso , Compostos Organometálicos/uso terapêutico , Adulto , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Compostos Radiofarmacêuticos/uso terapêutico , Qualidade de Vida , Pancreatectomia/métodosRESUMO
Preclinical data have shown that 161Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their 177Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose-response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [161Tb]Tb- and [177Lu]Lu-DOTATATE (agonist) and with [161Tb]Tb- and [177Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and ß- particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their 177Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by 161Tb. When activity concentrations were considered, both [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with 177Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose-response curves for [161Tb]Tb- and [177Lu]Lu-DOTATATE. [161Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [161Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by 161Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [161Tb]Tb-DOTATATE and [161Tb]Tb-DOTA-LM3 than for the 177Lu-labeled analogs. In contrast, [161Tb]Tb-DOTATATE showed no higher dose response than [177Lu]Lu-DOTATATE, whereas for [161Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [161Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [161Tb]Tb-DOTATATE for labeling with 161Tb.
Assuntos
Núcleo Celular , Elétrons , Octreotida , Compostos Organometálicos , Radioisótopos , Térbio , Humanos , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Elétrons/uso terapêutico , Térbio/química , Núcleo Celular/metabolismo , Radioisótopos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Lutécio , Relação Dose-Resposta à Radiação , Radiometria , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Background Somatostatin receptors, and specifically somatostatin receptor type 2 (SSTR2), have primarily been associated with neuroendocrine tumors and have revolutionized the imaging and therapy of patients with these tumors. SSTR2 is expressed on other tumors at lower prevalence. Purpose To evaluate the potential of SSTR2-targeted imaging and therapy in patients with breast cancer. Materials and Methods In a preclinical experiment, SSTR2 expression was assessed in tissue microarrays of breast cancer samples using H-score analysis. H-scores higher than 50 (0-300 scale) were considered positive. Then, a prospective phase 2 clinical trial of SSTR2-targeted tetraazacyclododecane tetraacetic acid octreotate (Dotatate) PET/CT was performed in participants with biopsy-proven estrogen receptor (ER)-positive breast cancer from January to August 2023. A positive Dotatate PET/CT scan was defined as tumors with a Krenning score of 3 (avidity greater than liver) or 4 (avidity greater than spleen). The proportion of positive scans and the 95% CI were calculated. One participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET/CT result underwent treatment with SSTR2-targeted actinium 225 (225Ac) Dotatate. Results Preclinical microarrays demonstrated that 63 of 123 ER-positive breast cancer tissue samples (51% [95% CI: 42, 60]) but only 22 of 121 ER-negative breast cancer tissue samples (18% [95% CI: 12, 26]) were enriched for SSTR2 (P < .001). Thirty female participants (mean age, 66 years ± 15) with metastatic ER-positive breast cancer were accrued to the phase 2 SSTR2-targeted imaging trial and underwent Dotatate PET/CT. Dotatate PET/CT demonstrated that nine of 30 participants (30% [95% CI: 15, 49]) had tumors with Krenning scores of 3 or 4, indicating strong SSTR2 expression. SSTR2-targeted therapy with alpha-emitting 225Ac-Dotatate resulted in a near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET result. Conclusion Molecular imaging targeting SSTR2 and radioligand therapy with SSTR2-targeted 225Ac-Dotatate enables a new therapeutic option for patients with metastatic breast cancer. Clinical trial registration no. NCT05880394 © RSNA, 2024 See also the editorial by Lin and Choyke in this issue.
Assuntos
Neoplasias da Mama , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Somatostatina , Humanos , Feminino , Receptores de Somatostatina/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Estudos Prospectivos , Idoso , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Radiofarmacêuticos , AdultoRESUMO
Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(ß), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(ß), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.
Assuntos
Miocardite , Miocárdio , Octreotida , Somatostatina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Aguda , Transporte Biológico , Diagnóstico Diferencial , Coração/diagnóstico por imagem , Miocardite/diagnóstico por imagem , Miocardite/metabolismo , Miocárdio/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Octreotida/análogos & derivados , Octreotida/metabolismo , Octreotida/farmacocinética , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/metabolismoRESUMO
ABSTRACT: A 76-year-old woman with liver and bone metastasis of a duodenal neuroendocrine tumor received peptide receptor radionuclide therapy with 177 Lu-DOTATATE. Scintigraphy with SPECT/CT performed 4 days after the treatment demonstrated 177 Lu-DOTATATE uptake as multifocal ground glass opacities in the bilateral lungs. This uptake was considered to be due to COVID-19 pneumonia because the patient was infected with the virus 7 days prior to the treatment. The lung opacities became smaller, showing a decreased uptake, 2 months later, after the second treatment. 177 Lu-DOTATATE may be taken up during the active phase of COVID-19 pneumonia.
Assuntos
COVID-19 , Pulmão , Octreotida , Compostos Organometálicos , Pneumonia Viral , Humanos , COVID-19/diagnóstico por imagem , COVID-19/complicações , Idoso , Feminino , Pulmão/diagnóstico por imagem , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/complicações , Pandemias , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/complicações , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapiaRESUMO
177Lu-DOTATATE is an effective second-line treatment for metastatic or nonresectable neuroendocrine tumors. This treatment can result in hematologic severe adverse reactions (SARs). Preemptive identification of patients at risk of SARs could mitigate this risk and improve treatment safety and outcomes. Methods: Demographic and oncologic history, pretreatment laboratory values, and SAR frequency were obtained for 126 sequential patients treated with 177Lu-DOTATATE. Univariable and multivariable logistic regression models identified factors correlating with SARs. Results: Relative pretreatment anemia, leukopenia, thrombocytopenia, and elevated mean corpuscular volume (MCV) were significantly correlated with SARs, with an odds ratio of 16 (95% CI, 5-65) in patients with an MCV greater than 95 fL. Conclusion: Pretreatment bone marrow dyscrasias, including an MCV greater than 95 fL, may predict patients at risk for SARs when treated with 177Lu-DOTATATE. Further study is needed to determine whether the risks of SARs outweigh the benefit in these patients.