Recurrent prostate cancer detection with <Emphasis Type="Italic">anti</Emphasis>-3-[<Superscript>18</Superscript>F]FACBC PET/CT: comparison with CT

Purpose

To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[¹⁸F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma.

Methods

This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT.

Results

Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %.

Conclusion

The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

     

Pilot Study of the Utility of the Synthetic PET Amino-Acid Radiotracer Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid for the Noninvasive Imaging of Pulmonary Lesions

Purpose

Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-3-[¹⁸F]FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in detection of prostate carcinoma and brain tumors and has also been shown to have uptake in lung tumor cell lines. The purpose of this study is to determine the uptake characteristics of anti-3-[¹⁸F]FACBC in lung carcinoma and if this radiotracer may help characterize pulmonary lesions.

Procedures

Ten patients with pulmonary lesions scheduled for surgical resection or biopsy underwent 45-min dynamic PET-CT imaging of the thorax after IV injection of 214.6–384.8MBq of anti-3-[¹⁸F]FACBC. Anti-3-[¹⁸F]FACBC uptake was compared with that of routine 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) PET-CT scans of the same patient and validated with a combination of pathology, imaging and clinical follow-up. Immunohistochemistry for Ki-67 was performed on tissue samples.

Results

There were nine malignant (seven lung nodules and two mediastinal nodes), two inflammatory, and one carcinoid lesion ranging from 1 to 3.75 cm. Mean(±SD) SUV_max of malignant lesions was 6.2(±2.6), 5.9(±2.7), 5.9(±3.4), and 5.7(±3.3), at 8, 16, 28, and 40 min, respectively; while for inflammatory lesions at the same time points, 4.1(±0.6), 3.3(±0.9), 2.2(±0.03), and 2.3(±0.03), respectively. The carcinoid tumor had SUV_max of 2.8, 2.6, 1.5, and 0.9 at similar time points. Mean SUV_max of all malignant lesions was higher than that of inflammatory lesions for anti-3-[¹⁸F]FACBC, and was statistically significant at greater than 28 min post-radiotracer infusion (p?<?0.05). There was no significant correlation of anti-3-[¹⁸F]FACBC activity with Ki67, though there was a positive trend. There was a strong correlation between anti-3-[¹⁸F]FACBC and [¹⁸F]FDG uptake.

Conclusions

Anti-3-[¹⁸F]FACBC uptake in malignant lesions is greater than in inflammatory lesions with a higher degree of separation of uptake on delayed imaging. More comprehensive study is required to determine the diagnostic performance of anti-3-[¹⁸F]FACBC in the characterization of pulmonary lesions.     

Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid

Introduction

The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[¹⁸F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-l (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[¹⁸F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans.

Methods

A DU145 xenograft rodent model was used to measure anti-2-[¹⁸F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[¹⁸F]FACPC-1 toxicity was assessed using a single microdose (37–74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247±61 MBq bolus injection of anti-2-[¹⁸F]FACPC-1. Estimates of radiation dose from anti-2-[¹⁸F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software.

Results

High anti-2-[¹⁸F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[¹⁸F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq.

Conclusion

Anti-2-[¹⁸F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting malignant tissues in these regions.     

Pilot Evaluation of Anti-1-amino-2-[18F] fluorocyclopentane-1-carboxylic acid (anti-2-[18F] FACPC) PET-CT in Recurrent Prostate Carcinoma

Molecular Imaging and Biology - Anti-1-amino-2-[18F]fluorocyclopentane-1-carboxylic acid (anti-2-[18F]FACPC) is an unnatural alicyclic amino acid radiotracer with high uptake in the DU-145 prostate...     

iRENEX: a clinically informed decision support system for the interpretation of 99mTc-MAG3 scans to detect renal obstruction

Purpose

Decision support systems for imaging analysis and interpretation are rapidly being developed and will have an increasing impact on the practice of medicine. RENEX is a renal expert system to assist physicians evaluate suspected obstruction in patients undergoing mercaptoacetyltriglycine (MAG3) renography. RENEX uses quantitative parameters extracted from the dynamic renal scan data using QuantEM?II and heuristic rules in the form of a knowledge base gleaned from experts to determine if a kidney is obstructed; however, RENEX does not have access to and could not consider the clinical information available to diagnosticians interpreting these studies. We designed and implemented a methodology to incorporate clinical information into RENEX, implemented motion detection and evaluated this new comprehensive system (iRENEX) in a pilot group of 51 renal patients.

Methods

To reach a conclusion as to whether a kidney is obstructed, 56 new clinical rules were added to the previously reported 60 rules used to interpret quantitative MAG3 parameters. All the clinical rules were implemented after iRENEX reached a conclusion on obstruction based on the quantitative MAG3 parameters, and the evidence of obstruction was then modified by the new clinical rules. iRENEX consisted of a library to translate parameter values to certainty factors, a knowledge base with 116 heuristic interpretation rules, a forward chaining inference engine to determine obstruction and a justification engine. A clinical database was developed containing patient histories and imaging report data obtained from the hospital information system associated with the pertinent MAG3 studies. The system was fine-tuned and tested using a pilot group of 51 patients (21 men, mean age 58.2?±?17.1?years, 100 kidneys) deemed by an expert panel to have 61 unobstructed and 39 obstructed kidneys.

Results

iRENEX, using only quantitative MAG3 data agreed with the expert panel in 87?% (34/39) of obstructed and 90?% (55/61) of unobstructed kidneys. iRENEX, using both quantitative and clinical data agreed with the expert panel in 95?% (37/39) of obstructed and 92?% (56/61) of unobstructed kidneys. The clinical information significantly (p?Conclusion Our renal expert system for detecting renal obstruction has been substantially expanded to incorporate the clinical information available to physicians as well as advanced quality control features and was shown to interpret renal studies in a pilot group at a standardized expert level. These encouraging results warrant a prospective study in a large population of patients with and without renal obstruction to establish the diagnostic performance of iRENEX.     

[18F]Fluciclovine PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging—version 1.0

European Journal of Nuclear Medicine and Molecular Imaging - The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of...