Highly Symptomatic Progressing Cardiac Paraganglioma With Intracardiac Extension Treated With 177Lu-DOTATATE: A Case Report.

Introduction: Primary cardiac paragangliomas are rare tumors. Metastatic disease is even rarer. Surgical management is technically challenging, and sometimes even impossible. Available therapeutic modalities for metastatic disease include external beam radiation therapy as well as systemic treatments, namely 131I-MIBG and more recently, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. To our knowledge, this is the first case of progressive unresectable cardiac paraganglioma with intracardiac extension treated with dosimetry based personalized PRRT to be reported. This case is of particular interest since it documents for the first time the efficacy, and especially the safety of the 177Lu-DOTATATE PRRT in this precarious context for which therapeutic options are limited. Case Presentation: A 47-year-old man with no medical history consulted for rapidly decreasing exercise tolerance. The investigation demonstrated an unresectable progressing metastatic cardiac paraganglioma with intracardiac extension. The patient was treated with personalized 177Lu-DOTATATE PRRT and showed complete symptomatic and partial anatomical responses, with a progression-free survival of 13 months. Conclusions: PRRT with 177Lu-DOTATATE should be considered for inoperable cardiac paraganglioma. No major hemodynamic complications were experienced. Therapy resulted in safety and substantially improved quality of life.

HIV-Infected Patient Diagnosed With Osteomedullary and Hepatic Syphilis on Positron Emission Tomography: A Case Report.

A human immunodeficiency virus (HIV)-positive man presented with a recent history of weight loss and B symptoms. Positron emission tomography (PET) scan revealed multiple hypercaptation foci, including diffuse osteomedullary lesions and a dominant liver nodule. Syphilis screening was positive, with a rapid plasma reagin (RPR) titer of 1:1,024. Following antibiotic therapy, repeat PET scan demonstrated complete resolution of hypermetabolic lesions, arguing toward an infectious etiology. Cases of disseminated syphilis characterized on nuclear imaging typically demonstrate radiological evidence of target tissue inflammation. PET scan could however also represent a sensitive modality for evaluation of early subclinical secondary syphilis.

Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297). METHODS: PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25-50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed. RESULTS: Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3-78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3-24.3) Gy and 185.7 (range: 15.2-443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47-2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity. CONCLUSIONS: Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

Accuracy and reproducibility of simplified QSPECT dosimetry for personalized 177Lu-octreotate PRRT.

BACKGROUND: Routine dosimetry is essential for personalized 177Lu-octreotate peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs), but practical and robust dosimetry methods are needed for wide clinical adoption. The aim of this study was to assess the accuracy and inter-observer reproducibility of simplified dosimetry protocols based on quantitative single-photon emission computed tomography (QSPECT) with a limited number of scanning time points. We also updated our personalized injected activity (IA) prescription scheme. METHODS: Seventy-nine NET patients receiving 177Lu-octreotate therapy (with a total of 279 therapy cycles) were included in our study. Three-time-point (3TP; days 0, 1, and 3) QSPECT scanning was performed following each therapy administration. Dosimetry was obtained using small volumes of interest activity concentration sampling for the kidney, the bone marrow and the tumor having the most intense uptake. Accuracy of the simplified dosimetry based on two-time-point (2TP; days 1 and 3, monoexponential fit) or a single-time-point (1TPD3; day 3) scanning was assessed, as well as that of hybrid methods based on 2TP for the first cycle and 1TP (day 1 or 3; 2TP/1TPD1 and 2TP/1TPD3, respectively) or no imaging at all (based on IA only; 2TP/no imaging (NI)) for the subsequent induction cycles. The inter-observer agreement was evaluated for the 3TP, 2TP, and hybrid 2TP/1TPD3 methods using a subset of 60 induction cycles (15 patients). The estimated glomerular filtration rate (eGFR), body size descriptors (weight, body surface area (BSA), lean body weight (LBW)), and products of both were assessed for their ability to predict IA per renal absorbed dose at the first cycle. RESULTS: The 2TP dosimetry estimates correlated highly with those from the 3TP data for all tissues (Spearman r > 0.99, P < 0.0001) with small relative errors between the methods, particularly for the kidney and the tumor, with median relative errors not exceeding 2% and interdecile ranges spanning over less than 6% and 4%, respectively, for the per-cycle and cumulative estimates. For the bone marrow, the errors were slightly greater (median errors < 6%, interdecile ranges < 14%). Overall, the strength of correlations of the absorbed dose estimates from the simplified methods with those from the 3TP scans tended to progressively decrease, and the relative errors to increase, in the following order: 2TP, 2TP/1TPD3, 1TPD3, 2TP/1TPD1, and 2TP/NI. For the tumor, the 2TP/NI scenario was highly inaccurate due to the interference of the therapeutic response. There was an excellent inter-observer agreement between the three observers, in particular for the renal absorbed dose estimated using the 3TP and 2TP methods, with mean errors lesser than 1% and standard deviations of 5% or lower. The eGFR · LBW and eGFR · BSA products best predicted the ratio of IA to the renal dose (GBq/Gy) for the first cycle (Spearman r = 0.41 and 0.39, respectively; P < 0.001). For the first cycle, the personalized IA proportional to eGFR · LBW or eGFR · BSA decreased the range of delivered renal absorbed dose between patients as compared with the fixed IA. For the subsequent cycles, the optimal personalized IA could be determined based on the prior cycle renal GBq/Gy with an error of less than 21% in 90% of patients. CONCLUSIONS: A simplified dosimetry protocol based on two-time-point QSPECT scanning on days 1 and 3 post-PRRT provides reproducible and more accurate dose estimates than the techniques relying on a single time point for non-initial or all cycles and results in limited patient inconvenience as compared to protocols involving scanning at later time points. Renal absorbed dose over the 4-cycle induction PRRT course can be standardized by personalizing IA based on the product of eGFR with LBW or BSA for the first cycle and on prior renal dosimetry for the subsequent cycles.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PURPOSE OF REVIEW: In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. RECENT FINDINGS: Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. SUMMARY: PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact of PSMA-targeted molecules are urgently needed.

Clinical relevance of 18F-FDG PET/CT lower-limb imaging in patients with malignant cutaneous melanoma.

OBJECTIVE: The aim of this study was to assess the clinical relevance of imaging the lower limbs when using 2-(F)-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography with computed tomography (PET/CT) for malignant cutaneous melanoma in patients without previously known or suspected primary or metastatic melanoma lesions in the lower limbs. PATIENTS AND METHODS: We retrospectively assessed 880 consecutive F-FDG PET/CT scans performed for adult patients in a context of suspected melanoma spanning a period of 5 years. All scans were correlated with the associated patient records (clinical history, physical examinations, and pathology reports), as well as follow-up imaging examinations, up until at least 6 months after the end of the study. RESULTS: Among the 461 whole-body scans included for analysis, 109 reported unusual activity in the lower limbs, but with at most 21 scans showing lower-limb lesions attributed to melanoma on follow-up. No scan showed melanoma lesions exclusively in the lower limbs, and in no case did imaging the lower limbs upstage a patient. Imaging the lower limbs changed the actual clinical management of the melanoma for only one patient, with precautionary local radiation therapy administered following the detection of an asymptomatic distal femur bone metastasis in an otherwise plurimetastatic patient headed for palliative care. CONCLUSION: Our study, the largest of its kind, confirms that, when using F-FDG PET/CT for staging, restaging, or surveillance of malignant cutaneous melanoma in patients without previously known or suspected lower-limb melanoma lesions, imaging the lower extremities offers little additional clinically relevant information and stopping the scan at the proximal thighs has essentially no clinical impact.

Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

Endovascular shear strain elastography for the detection and characterization of the severity of atherosclerotic plaques: in vitro validation and in vivo evaluation.

This work explores the potential of shear strain elastograms to identify vulnerable atherosclerotic plaques. The Lagrangian speckle model estimator (LSME) elasticity imaging method was further developed to estimate shear strain elasticity (SSE). Three polyvinyl alcohol cryogel vessel phantoms were imaged with an intravascular ultrasound (IVUS) scanner. The estimated SSE maps were validated against finite-element results. Atherosclerosis was induced in carotid arteries of eight Sinclair mini-pigs using a combination of surgical techniques, diabetes and a high-fat diet. IVUS images were acquired in vivo in 14 plaques before euthanasia and histology. All plaques were characterized by high magnitudes in SSE maps that correlated with American Heart Association atherosclerosis stage classifications (r = 0.97, p < 0.001): the worse the plaque condition the higher was the absolute value of SSE, i.e. |SSE| (e.g., mean |SSE| was 3.70 ± 0.40% in Type V plaques, whereas it was reduced to 0.11 ± 0.01% in normal walls). This study indicates the feasibility of using SSE to highlight atherosclerotic plaque vulnerability characteristics.

Vulnerable atherosclerotic carotid plaque evaluation by ultrasound, computed tomography angiography, and magnetic resonance imaging: an overview.

Ischemic syndromes associated with carotid atherosclerotic disease are often related to plaque rupture. The benefit of endarterectomy for high-grade carotid stenosis in symptomatic patients has been established. However, in asymptomatic patients, the benefit of endarterectomy remains equivocal. Current research seeks to risk stratify asymptomatic patients by characterizing vulnerable, rupture-prone atherosclerotic plaques. Plaque composition, biology, and biomechanics are studied by noninvasive imaging techniques such as magnetic resonance imaging, computed tomography, ultrasound, and ultrasound elastography. These techniques are at a developmental stage and have yet to be used in clinical practice. This review will describe noninvasive techniques in ultrasound, magnetic resonance imaging, and computed tomography imaging modalities used to characterize atherosclerotic plaque, and will discuss their potential clinical applications, benefits, and drawbacks.

Prospective study on the treatment of lower-extremity chronic venous and mixed ulcers using tissue-engineered skin substitute made by the self-assembly approach.

BACKGROUND: Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers. PATIENTS AND METHODS: The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient's own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution. RESULTS: Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care. CONCLUSION: The authors' study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.