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This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed.
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Embolización Terapéutica , Neoplasias Hepáticas , Radiofármacos , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Embolización Terapéutica/métodos , Radiofármacos/uso terapéutico , Radioisótopos de Itrio/uso terapéutico , Hígado/diagnóstico por imagenRESUMEN
BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Persona de Mediana Edad , Radioisótopos de Galio , Isótopos de Galio , Biopsia , Estudios de Cohortes , Imagen por Resonancia Magnética/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Clasificación del Tumor , Estudios Retrospectivos , Antígeno Prostático Específico/sangre , Valor Predictivo de las PruebasRESUMEN
INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.
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Arteria Hepática , Infusiones Intraarteriales , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/administración & dosificación , Arteria Hepática/diagnóstico por imagen , Incidencia , Bombas de Infusión Implantables , Circulación Hepática , Neoplasias Hepáticas/cirugía , Azul de Metileno/administración & dosificación , Países Bajos/epidemiología , Estudios Retrospectivos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Agregado de Albúmina Marcado con Tecnecio Tc 99m/administración & dosificaciónRESUMEN
PURPOSE OF REVIEW: To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. RECENT FINDINGS: Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations.
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Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/radioterapia , Receptores de Péptidos , Radiofármacos/uso terapéutico , Radioisótopos/uso terapéutico , Terapia CombinadaRESUMEN
PURPOSE: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. MATERIALS AND METHODS: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. RESULTS: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). CONCLUSION: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. TRAIL REGISTRATION: NCT01031784, registered December 2009. NCT01612325, registered June 2012.
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Embolización Terapéutica , Neoplasias Hepáticas , Neumonitis por Radiación , Humanos , Estudios Prospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único , Neumonitis por Radiación/etiología , Neumonitis por Radiación/tratamiento farmacológico , Radioisótopos de Itrio/uso terapéutico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Embolización Terapéutica/efectos adversos , Pulmón/diagnóstico por imagen , Microesferas , Estudios RetrospectivosRESUMEN
Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Radioisótopos de Itrio/uso terapéutico , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/radioterapia , Colangiocarcinoma/tratamiento farmacológico , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/radioterapia , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares Intrahepáticos , MicroesferasRESUMEN
PURPOSE: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. METHODS: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. RESULTS: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. Dh was associated with biochemical toxicity (p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. CONCLUSION: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.
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BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Microesferas , Estudios Prospectivos , Calidad de Vida , Neoplasias Hepáticas/radioterapia , Hepatomegalia , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: For safe and effective holmium-166 (166Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166Ho and technetium-99m stannous-phytate accumulating in healthy liver cells (166Ho-99mTc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99mTc images derived from a 166Ho-99mTc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99mTc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166Ho SPECT to compute absorbed dose in healthy liver. RESULTS: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity. CONCLUSIONS: 166Ho-99mTc dual-isotope protocol can automatically segment the healthy liver without hampering the 166Ho dosimetry assessment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988.
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BACKGROUND: With the introduction of prostate specific membrane antigen (PSMA) PET/CT, the detection rate of prostate cancer metastases has improved significantly, both for primary staging and for biochemical recurrence. EANM/SNMMI guidelines recommend a 60 min time interval between [68 Ga]Ga-PSMA administration and acquisition. PURPOSE: This study evaluates the possibility of a shorter time interval by investigating the dynamic change in image quality measures. METHOD: We retrospectively analyzed 10 consecutive prostate cancer patients who underwent a dynamic whole body [68 Ga]Ga-PSMA-11 PET/CT of 75 min from skull vertex to mid-thigh using Siemens FlowMotion. PET images were acquired directly after injection of 1.5 MBq/kg [68 Ga]Ga-PSMA-11. Image quality measures included lesion maximum standardized uptake value corrected for lean body mass (SULmax ), tumor-to-background ratio (TBR), and contrast-to-noise ratio (CNR). Quantitative analysis of image quality in dynamic PET was performed using PMOD (version 4.2). Regions of interest (ROIs), drawn included different types of prostate lesions (primary tumor, lymph nodes, and bone metastasis), organ tissue (liver, spleen, lacrimal gland, submandibular gland, parotid gland, urinary bladder, kidneys blood pool [ascending aorta], left ventricle), bone tissue (4th lumbar vertebral body [L4]) and muscle tissue (gluteus maximus). To further investigate image quality four 10 min multi-frame reconstructions with clinical parameters were made at different post-injection times (15, 30, 45, and 60 min). A nuclear medicine physician performed a blinded lesion detectability evaluation on these multi-frame reconstructions for different prostate cancer lesions. RESULTS: Six primary prostate tumors in seven patients with prostate in situ, 13 lymph node metastases in six patients and up to 12 bone metastases in three patients were found. The different prostate lesion types (lymph nodes metastases, bone metastases, and primary prostate tumor) all show an increase in average SULmax , TBR, and CNR over time during the scan. The normalized average SULmax , TBR, and CNR of the combined prostate lesions at 15, 30, and 45 min post-injection scans were all significant p < 0.05 lower from the 60 min post-injection [68 Ga]Ga-PSMA-11 PET/CT (9.5 ± 4.5, 12.7 ± 6.2, and 41.8 ± 24.5, respectively). At patient level, the reader concluded the same regarding the presence/absence of primary prostate cancer recurrence, lymph node metastases, and/or bone metastases on all <60 min post-injection [68 Ga]Ga-PSMA-11 PET/CT's in comparison to the reference scan (60 min post-injection). At lesion level, all bone metastases seen on the reference scan were also seen on all <60 min post-injection [68 Ga]Ga-PSMA-11 PET/CT's but there were some lymph nodes (n = 2) metastases missed on the 15, 30, and 45 min post-injection scans. One lymph node metastasis on both the 15 and 30 min post-injection [68 Ga]Ga-PSMA-11 PET/CT's was missed and one lymph node metastasis was missed, only on the 45 min post-injection [68 Ga]Ga-PSMA-11 PET/CT. CONCLUSION: Shorter post-injection times (15, 30, and 45 min) compared to the recommended post-injection time of 60 min are not optimal. However, the impact of a shorter time interval of 45 min instead of 60 min between [68 Ga]Ga-PSMA-11 administration and the start of PET/CT acquisition on both image quality (SULmax , TBR, and CNR) and lesion detection, while significant, is small.
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Neoplasias Óseas , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioisótopos de Galio , Metástasis Linfática/diagnóstico por imagen , Isótopos de Galio , Estudios Retrospectivos , Oligopéptidos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patologíaRESUMEN
Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours.
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Creatina , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estudios de Factibilidad , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Protones , Amidas/química , AminasRESUMEN
Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is a new treatment in The Netherlands. Patients with metastasized castration resistant prostate carcinoma and progressive disease after hormonal therapy and chemotherapy, and no other regular therapeutic options, can be referred. A good clinical performance state, adequate bone marrow function and a PSMA PET/CT showing adequate targeting in all metastases are essential. The therapy consists of four to six intravenous administrations of 7.4 GBq [177Lu]Lu-PSMA, six weeks apart. Side effects are mild and consist of xerostomia, fatigue and bone marrow depression. This therapy is currently administered only in a few hospitals in The Netherlands, mainly in research setting. An EMA registered product is expected at the end of 2022, which can contribute to better availability for reimbursed treatment.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Próstata/patología , Antígeno Prostático Específico , Dipéptidos/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Radiofármacos/efectos adversosRESUMEN
Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.
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Anticuerpos Monoclonales , Staphylococcus aureus , Animales , Ratones , Staphylococcus aureus/metabolismo , Distribución Tisular , Anticuerpos Monoclonales/uso terapéutico , Tomografía Computarizada de Emisión de Fotón Único/métodos , QuelantesRESUMEN
BACKGROUND: Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [177Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [177Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields. METHODS: The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [177Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [177Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [177Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [177Lu]Lu-PSMA-617. DISCUSSION: This is the first prospective study to combine EBRT and ADT with [177Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [177Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments. TRIAL REGISTRATION: ClinicalTrials, NCT05162573 . Registered 7 October 2021.
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Neoplasias de la Próstata Resistentes a la Castración , Calidad de Vida , Humanos , Masculino , Antagonistas de Andrógenos/uso terapéutico , Teorema de Bayes , Dipéptidos/efectos adversos , Compuestos Heterocíclicos con 1 Anillo/efectos adversos , Estudios Prospectivos , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Resultado del TratamientoRESUMEN
Lutetium-177 coupled with a ligand for Prostate Specific Membrane Antigen ([177Lu]Lu-PSMA) is a new treatment in The Netherlands. Patients with metastasized castration resistant prostate carcinoma and progressive disease after hormonal therapy and chemotherapy, and no other regular therapeutic options, can be referred. A good clinical performance state, adequate bone marrow function and a PSMA PET/CT showing adequate targeting in all metastases are essential. The therapy consists of four to six intravenous administrations of 7.4 GBq [177Lu]Lu-PSMA, six weeks apart. Side effects are mild and consist of xerostomia, fatigue and bone marrow depression. This therapy is currently administered only in a few hospitals in The Netherlands, mainly in research setting. An EMA registered product is expected at the end of 2022, which can contribute to better availability for reimbursed treatment.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Próstata/patología , Antígeno Prostático Específico , Dipéptidos/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Radiofármacos/efectos adversosRESUMEN
Background: Immunotherapy in the form of checkpoint inhibitors has changed the treatment paradigm in oncology. Combining selective internal radiation therapy (SIRT) with immunotherapy has been suggested to potentially improve outcomes in hepatocellular carcinoma (HCC) and metastatic colorectal carcinoma (mCRC). In this systematic review, the authors discuss the current developments and available clinical data regarding the combination of immunotherapy and SIRT in treating hepatic malignancies. Methods: PubMed, Embase, and Cochrane library were systematically searched for eligible studies (adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines). Original patient studies written in English language with patients with HCC or mCRC who were treated with SIRT and immunotherapy were included. Endpoints evaluated included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: 1038 publications were screened, from which 1034 publications were excluded. Four studies with a total of 87 patients were included in this systematic review, of which two consisted of mCRC and the other two HCC. All four studies showed no increased toxicities of the combination therapy over known data on monotherapy. One mCRC study reported a median OS of 8 months, while the other mCRC study ended due to futility. Both reported an ORR of 0%. The two HCC studies reported a median OS of 16.5 and 16.2 months. Median PFS was 5.6 and 5.7 months. ORR ranged from 31% to 80%. Conclusion: The combination of SIRT and immunotherapy has been studied in four early-phase studies showing a favorable safety profile. Further studies are necessary to understand the possible synergy and possible benefit of combination therapy.
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Carcinoma Hepatocelular , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Combinada , Neoplasias Colorrectales/tratamiento farmacológico , InmunoterapiaRESUMEN
PSMA PET/CT is a diagnostic technique for patients with prostate cancer. It makes use of a radioligand that specifically binds to 'prostate specific membrane antigen' (PSMA), expressed by the prostate cancer cells. PSMA PET has proven to be highly effective in prostate cancer diagnostics in both primary staging and re-staging. PSMA PET/CT has a much higher accuracy than traditional CT and skeletal scintigraphy for the detection of metastases, allowing metastases to be detected in an earlier stage. The clinical relevance of the improved detection is now under investigation. Staging with PSMA PET/CT sometimes leads to avoiding surgery because distant metastases are found that were not detected with conventional imaging. In the Netherlands, PSMA PET/CT is now indicated both in primary prostate cancer diagnostics for the detection of metastases and for the detection of biochemical recurrence after prostatectomy or after radiotherapy.
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Antígeno Prostático Específico , Próstata , Neoplasias de la Próstata , Cintigrafía , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/diagnóstico por imagen , Antígeno Prostático Específico/análisis , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Cintigrafía/métodosRESUMEN
PURPOSE: The study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy. METHODS: A PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author's country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated. RESULTS: A total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control. CONCLUSION: FAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.