Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Preliminary Study on Quantitative Evaluation of Myocardial Fibrosis by CardiacMagnetic Resonance in Patients with Light Chain Cardiac Amyloidosis / 罕见病研究

  Objective  Myocardial fibrosis is a potential mechanism of light-chain myocardial amyloidosis(AL-CA). This research aimed at exploring the correlation between multiparameter cardiac magnetic resonance (CMR) and myocardial fibrosis by relating the CMR myocardial tissue characteristics, the morphological and the functional parameters with gallium-68-labeledfibroblast activation protein inhibitor 04 positron emission tomography (68Ga-FAPI PET).  Methods  We gave the patients diagnosed with AL-CA in Peking Union Medical College Hospital from August to December 2021 the examinations of CMR and 68Ga-FAPI PET/CT. We recorded and analyzed the information on clinical manifestations and examinations of the patients.  Results  A total of 23 patients with AL-CA were included, 15 (65.2%)of which were male and the mean age was 58.3±6.5 years. Patients with high 68Ga-FAPI-04 uptake had shown growth in myocardial extracellular volume (ECV), significantly higher than those in the negative group (P=0.047). In addition, patients' myocardial ECV was positively correlated with myocardial FAPI uptake (r=0.628, P=0.001;r=0.727, P < 0.001;r=0.661, P=0.001). Patients in the positive group showd reduced left ventricular (LV) ejection fraction (EF)(P < 0.001).LVEF (r=-0.798, P < 0.001;r=-0.794, P < 0.001; r=-0.795, P < 0.001) and right ventricular (RV)EF (r=-0.735, P < 0.001;r=-0.739, P < 0.001;r=- 0.684, P < 0.001) showd negatively correlated with myocardial FAPI uptake, LV circumferential strain (r=0.668, P < 0.001;r=0.708, P < 0.001;r=0.705, P < 0.001), LV longitudinal strain (r=0.629, P=0.001;r=0.635, P=0.001; r=0.597, P=0.003), and RV longitudinal strain (r=0.575, P=0.004; r=0.792, P < 0.001;r=0.673, P < 0.001) were negatively correlated with myocardial FAPI uptake.  Conclusions  FAPI-related fibroblast activation is concurrent with CMR-related abnormal myocardial interstitial characteristics that leads to the decreased function of the myocardial movement. Patients with increased FAPI uptake present with increased ECV, decreased EF, and decreased strain with morphological abnormalities.

Detection of Neuroendocrine Tumour of Sphenoid Sinus on the Gallium-68 DOTATATE PET/CT: A Rare Entity

@#Neuroendocrine tumours (NETs) are a category of neoplasm that is characterised by its phenotypic and heterogeneity. The occurrence of this type of neoplasm in the nasal cavity and paranasal sinuses is extremely rare accounting for only 0.2-0.8% of all cancers. NET tends to expresses somatostatin receptors (SSTR) and owning to this unique characteristic, molecular imaging has been able to detect these tumours using radiolabelled somatostatin analogue agent. Gallium-68 (Ga-68) DOTATATE PET/CT is an example of SSTR imaging and has been shown to be of importance in the assessment and staging of NET. We present a case of a rare sphenoid sinus NET in a 45-year-old gentleman whom initially presented with persistent left eye pain which led to visual loss. We described the utilization of Ga-68 DOTATATE PET/CT in the diagnosis and staging of this patient which in turn dictated treatment approach.

Intramastoid Phosphaturic Mesenchymal Tumor Causing Hypophosphatemic Osteomalacia Detected on ⁶⁸Ga-DOTATATE PET/CT But Not on (99m)Tc-Sestamibi and ¹⁸F-FDG Scans / 대한핵의학회잡지

⁶⁸Ga-DOTATATE uptake in mesenchymal tumors causing hypophosphatemic osteomalacia has been recently described. Herein, we present a case of ⁶⁸Ga-DOTATATE uptake in an intramastoid phosphaturic mesenchymal tumor that had not been depicted in previous (99m)Tc-Sestamibi and ¹⁸F-FDG scans. The lesion was surgically removed and the phosphorus level increased to the normal range.

Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better Characterized on ¹⁸F-Fluoride PET/CT than on ⁶⁸Ga-Dotatate PET/CT / 대한핵의학회잡지

Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12 years of age. The patient had previously undergone total thyroidectomy, cervical radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and lymph node metastases and was scanned with ¹⁸F-fluoride (¹⁸F-NaF) and ⁶⁸Ga-dotatate whole-body positron emission tomography/computed tomography (PET/CT) for metastatic disease monitoring.We found that the MTC bone metastases and soft tissue calcified metastases were better characterized on ¹⁸F-NaF PET/CT than on ⁶⁸Ga-dotatate PET/CT. This case illustrates that the ¹⁸F-NaF PET/CT could be helpful not only to the detection of bone metastases but also to the detection of calcified soft tissue metastases in patients with MTC.

Gammagrafía de receptores de somatostatina con -DOTATATE PET/CT: experiencia inicial en Cuba / Somatostatin receptor scintigraphy with -DOTATATE PET/CT: initial experience in Cuba

En 1870 Rudolf Heidenhain descubrió las células neuroendocrinas, las cuales dan origen a los Tumores Neuroendocrinos (TNE) que son una forma rara de cáncer, la mayoría de los cuales expresan receptores de somatostatina. El fundamento de la Gammagrafía de Receptores como imagen metabólico-molecular se fundamenta en el empleo de -DOTA-péptidos con enlazamiento específico a los receptores de somatostatina. La presente publicación tiene el propósito de dar a conocer nuestras primeras experiencias en el estudio de diferentes tipos histológicos de TNE por medio de la Gammagrafía de Receptores de Somatostatina (GRS) empleando el -DOTATATE PET/CT realizados en el Centro PET/CT e incluyendo Imagen Molecular del Departamento de Medicina Nuclear del Instituto Nacional de Oncología y Radiobiología (Inor)

In 1870, Rudolf Heidenhain discovered neuroendocrine cells, which can lead to the development of the Neuroendocrine Tumors (NER), a rare form of cancer, most of which express somatostatin receptors. The basis of Receptor Scintigraphy as a metabolic-molecular image is based on the use of -DOTA-peptides with specific binding to somatostatin receptors.The purpose of this publication is to present our first experiences in the study of different histological types of TNE by means of Somatostatin Receptor Scintigraphy (GRS) using -DOTATATE performed at the PET / CT Center and Molecular Image of the Department of Nuclear Medicine of the National Institute of Oncology and Radiobiology (Inor)

Uso de solventes no acuosos en la síntesis del radioconjugado DOTA-1-Nal3-octreotida marcado con galio-68 / Use of non-aqueous solvents in the synthesis of radioconjugate DOTA-1-Nal3-octreotide labeled with gallium-68

Los tumores neuroendocrinos sobreexpresan receptores de somatostatina. Su diagnóstico se ha extendido debido al radiomarcaje de DOTA-péptidos como el análogo de somatostatina DOTA-1--octreotida (DOTA-NOC) conjugado con radionúclidos emisores ß+ como el , de propiedades físico-nucleares muy favorables. El presente trabajo describe los procedimientos para el radiomarcaje del DOTA-NOC con , en medio acuoso puro y en presencia de solventes no acuosos, así como los métodos usados para el control de calidad, donde se obtuvo una formulación con un rendimiento radioquímico superior al 95 %. La adición de etanol (30%- vol/vol) a la mezcla de reacción permitió incrementar la actividad específica del radioconjugado -DOTA-NOC, y se alcanzó un valor de 182 MBq/nmol, superior al reportado en la literatura (50 MBq/nmol) para el marcaje en medio acuoso puro. También se presentan los estudios de estabilidad (en presencia de solución salina y tampón fosfato salino), estudios de transmetalación en soluciones de , , y , competencia por retos contra los quelatos EDTA y DTPA y estabilidad in vitro en transferrina humana, realizados al radioconjugado -DOTA-NOC, del cual se mostró su elevada estabilidad (> 95 %). En comparación con el medio acuoso puro, el uso de solventes no acuosos en la síntesis del radioconjugado DOTA-1--octreotida marcado con galio-68, permite disminuir la masa de conjugado y los tiempos de reacción, incrementar significativamente los rendimientos y la actividad específica del compuesto marcado. Ello pudiera favorecer la obtención del producto con mejores características en sistemas modulares que se encuentran en fase de desarrollo.

Neuroendocrine tumors specifically over-express somatostatin receptors. Their diagnosis has expanded due to radiolabelling of DOTA-peptides such as somatostatin analogue DOTA-1--Octreotide (DOTA-NOC) conjugated to ß+ emitting radionuclides such as , with very favorable decay-properties. This paper describes the radiolabeling procedures of DOTA-NOC with , in a pure aqueous medium and in presence of non-aqueous solvents as well as the methods used for quality control where a formulation is obtained with a radiochemical yield exceeding 95%. Adding ethanol (30 % - v / v) to the reaction mixture allowed increasing the specific activity of -DOTA-NOC radioconjugated, reaching a value of 182 MBq / nmol, higher than reported in literature (50 MBq / nmol) for labeling in a pure aqueous medium. Stability studies are also presented (in presence of saline solution and saline phosphate buffer, transmetallation studies in , , and solutions, challenges competition against EDTA and DTPA chelators and in vitro stability in human transferrin) performed to -DOTA-NOC radioconjugated, showing its high stability (> 95 %). Compared with the aqueous medium, the use of non aqueous solvents in the synthesis of radioconjugate DOTA-1--octreotide labeled with gallium-68, helps reduce the mass of conjugate and the reaction time, significantly increase yields and specific activity of the labeled compound. This could facilitate obtaining the product with better characteristics in modular systems that are under development.

Radiofármacos de galio 68 / Gallium radiopharmaceuticals 68

La tomografía de emisión de positrones (PET) es una técnica de imagen médica de gran sensibilidad y resolución, que requiere radionúclidos emisores de positrones de corta vida. Los más comúnmente usados son el 18F y el 11C. La principal dificultad de estos radionúclidos es la necesidad de instalar un ciclotrón en el sitio de uso o a distancias no muy grandes de este, por lo que se han investigado radionúclidos más convenientes como el 68Ga. Su disponibilidad a partir de los sistemas generadores de larga vida ? / 68Ga, de los que se obtiene Ga3+, utilizable durante tiempo un prolongado en sitios alejados del ciclotrón y la rica química de coordinación del 68Ga+, han posibilitado la incorporación a la práctica médica de algunos radiofármacos, así como la investigación de una variedad de complejos estables de Ga3+ acoplados ...

PET (positron emission tomography) is a technique of medical image of great sensibility and high resolution that requires short-lived positron emitting radionuclides. The most commonly used are 18F and 11C.The main difficulty of these radionuclides is the necessity to install a cyclotron in the site of use or not very far from it. Therefore convenient radionuclides have been researches, among them 68Ga. The availability of this radionuclide from long-lived ? / 68Ga generators, which can been used for along time far from the cyclotron location, and the rich coordination chemistry of 68Ga have allowed to incorporate to the medical practice some radiopharmaceuticals as well as the research of a variety of stables complexes of Ga3+ coupled to biomolecules for diagnostic imaging of cancer and cardiovascular and neurological diseases. The present work is aimed at examining the potentialities of the...

Role of (68)Ga-DOTATOC PET/CT in the Evaluation of Primary Pulmonary Carcinoids

BACKGROUND/AIMS: Although carcinoid tumors usually have good prognosis, early and specific diagnosis is important. Computed tomography and magnetic resonance imaging do not provide findings that are specific for carcinoids, and somatostatin receptor scintigraphy suffers from low spatial resolution. 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has limited sensitivity for carcinoids due to low uptake of the marker. A PET/CT system that uses the somatostatin receptor-based PET tracer 1,4,7,10-tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid (D)-Phe(1)-thy(3)-octreotide ((68)Ga-DOTATOC) has also been used in the evaluation of carcinoids, although information regarding its use for the detection of primary pulmonary carcinoids is limited. Thus, we investigated the value of (68)Ga-DOTATOC PET/CT for the diagnosis of primary pulmonary carcinoid tumors. METHODS: This was a retrospective analysis of patients with primary pulmonary tumors who underwent (68)Ga-DOTATOC PET/CT. All the patients had a histopathologic diagnosis of carcinoid. The rate of detection of primary pulmonary carcinoid tumors using (68)Ga-DOTATOC PET/CT was assessed. RESULTS: Twenty patients were diagnosed as having carcinoid, and 19 tumors showed significant uptake on (68)Ga-DOTATOC (detection rate, 95%). The maximal standardized uptake value (SUV(max)) ranged from 1.1 to 66, with a median value of 21.6. In one patient, (68)Ga-DOTATOC PET/CT revealed additional lesions. CONCLUSIONS: Our results demonstrate that (68)Ga-DOTATOC PET/CT is useful in the evaluation of primary pulmonary carcinoids and should be included in the diagnostic work-up of these patients.