Molecular Imaging of Urogenital Diseases

doi:10.1053/j.semnuclmed.2013.10.008

Seminars in Nuclear Medicine

Volume 44, Issue 2, March 2014, Pages 93-109

https://doi.org/10.1053/j.semnuclmed.2013.10.008 Get rights and content

There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutic options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional CT and bone scan is becoming increasingly important for both clinical management and drug development. PET radiotracers, apart from ¹⁸F-FDG, for prostate cancer are ¹⁸F-sodium fluoride, ¹¹C-choline, and ¹⁸F-fluorocholine, and ¹¹C-acetate. Other emerging and promising PET radiotracers include a synthetic l-leucine amino acid analogue (anti–¹⁸F-fluorocyclobutane-1-carboxylic acid), dihydrotestosterone analogue (¹⁸F-fluoro-5α-dihydrotestosterone), and prostate-specific membrane antigen–based PET radiotracers (eg, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-¹⁸F-fluorobenzyl-l-cysteine, ⁸⁹Zr-DFO-J591, and ⁶⁸Ga [HBED-CC]). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Although renal cell cancer imaging with FDG-PET/CT is available, it can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX)-based antibody (¹²⁴I-girentuximab) and radioimmunotherapy targeting with ¹⁷⁷Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-¹⁸F-fluorohippurate, hippurate m-cyano-p-¹⁸F-fluorohippurate, and rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin-angiotensin system with a variety of selective PET radioligands is also becoming available for clinical translation.

Section snippets

Glucose Metabolism

Detection of prostate cancer using ¹⁸F-FDG for glucose metabolism is limited for detection of primary disease and local recurrence owing to low sensitivity and overlap with prostatitis and benign prostatic hypertrophy.6, 7 FDG-PET is not recommended for detection of metastatic disease, especially for soft tissue metastases, in routine management of prostate cancer.⁸ However, the use of FDG-PET for detection of metastatic disease in the clinical setting of PSA relapse after RP was optimized to

Fluorocyclobutane-1-Carboxylic Acid

Anti-1-amino-3-¹⁸F-fluorocyclobutane-1-carboxylic acid (anti–¹⁸F-FACBC) is a synthetic l-leucine amino acid analogue that is taken up in prostate cancer cells by amino acid transporter system, ASCT2, and to a lesser by sodium-coupled neutral amino acid transporters but not incorporated into proteins intracellularly.³⁹ The initial clinical study of anti–¹⁸F-FACBC demonstrated uptake in primary prostate and metastatic disease.⁴⁰ Subsequent clinical study comparing anti–¹⁸F-FACBC with ¹¹¹

Fluoro-5α-Dihydrotestosterone

An analogue of dihydrotestosterone, 16β-¹⁸F-fluoro-5α-dihydrotestosterone (¹⁸F-FDHT), is the primary ligand for AR, which can noninvasively image AR expression.⁴² An initial study of 7 patients with progressive metastatic CRPC demonstrated an ¹⁸F-FDHT detection rate of 78% of the lesions compared with conventional imaging in patients with progressive CRPC with average lesion SUV_max of 5.28.⁴³ Another early study also demonstrated ¹⁸F-FDHT uptake at sites of metastatic disease, which after

Prostate-Specific-Membrane Antigen

PSMA is a type II integral membrane protein expressed on the surface of prostate cancer cells, also called glutamate carboxypeptidase II and folate hydrolase.⁴⁸ PSMA is a promising and a biologically established biomarker specifically associated with prostate cancer aggressiveness. Histologic studies have associated high PSMA expression with metastatic spread,49, 50, 51 androgen independence,⁵² and expression levels have be found to be predictive of prostate cancer progression.53, 54 The first

Glucose Metabolism

Clear cell renal cell carcinoma (RCC) is the most frequent malignant tumor of the kidneys, whereas papillary (chromophil) RCC, chromophobe RCC, and collecting duct–type RCCs are less common. Malignant tumors in the kidneys of nonrenal epithelial origin include lymphomas, malignant fibrous histiocytomas, and angiolipomas. Best treatment of RCC is surgery in early stages but owing to its high metastatic potential, the overall prognosis of RCC is poor.⁷⁵ Novel medical therapies that are based on

Molecular Biology

Acute kidney injury (AKI) has many etiologies including ischemia-reperfusion, infection, and acute radiation. Development of injury is rapid and changes in renal function occur early. Fast determination of the cause and rapid intervention are essential to minimize risk of nephron loss. The number of nephrons in the human kidneys is set at birth and can only decrease with aging and illnesses.¹¹⁹ Increased serum creatinine or decreased creatinine clearance may not be sensitive enough to detect

Bladder Cancer

Bladder carcinoma is the most frequent type of tumor of the urinary tract and is most prevalent in the fifth to seventh decade of life.¹ A systematic review and meta-analysis of application of FDG-PET and PET/CT in urinary bladder cancer was published by Lu et al¹⁵⁵. This study reviewed studies published from 2000 through 2010 and selected 6 eligible studies for meta-analysis, which found good diagnostic accuracy of FDG-PET and PET/CT for detection of metastatic bladder cancer. The pooled

References (156)

J.R. Walczak et al.
Prostate cancer: A practical approach to current management of recurrent disease
Mayo Clin Proc
(2007)
I.J. Liu et al.
Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer
Urology
(2001)
M.J. Morris et al.
Fluorinated deoxyglucose positron emission tomography imaging in progressive metastatic prostate cancer
Urology
(2002)
A. Ramirez de Molina et al.
Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers
Commun
(2002)
M. Yoshimoto et al.
Radiolabeled choline as a proliferation marker: Comparison with radiolabeled acetate
Nucl Med Biol
(2004)
S.A. Kwee et al.
Cancer imaging with fluorine-18-labeled choline derivatives
Semin Nucl Med
(2007)
M. Tuncel et al.
[(11)C]Choline positron emission tomography/computed tomography for staging and restaging of patients with advanced prostate cancer
Nucl Med Biol
(2008)
L. Evangelista et al.
Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: A systematic literature review and meta-analysis
Eur Urol
(2013)
M.H. Umbehr et al.
The role of ¹¹C-choline and ¹⁸F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: A systematic review and meta-analysis
Eur Urol
(2013)
C. Fuccio et al.
Choline PET/CT for prostate cancer: Main clinical applications
Eur J Radiol
(2011)

H.I. Scher et al.

Antitumour activity of MDV3100 in castration-resistant prostate cancer: A phase 1-2 study

Lancet

(2010)

S.S. Chang et al.

Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma

Urology

(2001)

S.D. Sweat et al.

Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases

Urology

(1998)

G.L. Wright et al.

Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy

Urology

(1996)

S. Perner et al.

Prostate-specific membrane antigen expression as a predictor of prostate cancer progression

Human Pathol

(2007)

J.R. Osborne et al.

Prostate-specific membrane antigen-based imaging

Urol Oncol

(2013)

R.L. Wahl et al.

Imaging of renal cancer using positron emission tomography with 2-deoxy-2-(18F)-fluoro-d-glucose: Pilot animal and human studies

J Urol

(1991)

S. Tatli et al.

PET/CT-guided percutaneous biopsy of abdominal masses: Initial experience

J Vasc Interv Radiol

(2011)

A. Jemal et al.

Cancer statistics, 2010

CA Cancer J Clin

(2010)

O. Sartor et al.

Unmet needs in the prediction and detection of metastases in prostate cancer

Oncologist

(2013)

T.A. Yap et al.

The changing therapeutic landscape of castration-resistant prostate cancer

Nat Rev Clin Oncol

(2011)

E.D. Crawford et al.

Optimizing outcomes of advanced prostate cancer: Drug sequencing and novel therapeutic approaches

Oncology (Williston Park)

(2012)

C. Hofer et al.

Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy

Eur Urol

(1999)

H. Schoder et al.

2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy

Clin Cancer Res

(2005)

M.J. Morris et al.

Fluorodeoxyglucose positron emission tomography as an outcome measure for castrate metastatic prostate cancer treated with antimicrotubule chemotherapy

Clin Cancer Res

(2005)

G.S. Meirelles et al.

Prognostic value of baseline [18F] fluorodeoxyglucose positron emission tomography and ^99mTc-MDP bone scan in progressing metastatic prostate cancer

Clin Cancer Res

(2010)

K.K. Wong et al.

Dynamic bone imaging with ^99mTc-labeled diphosphonates and 18F-NaF: Mechanisms and applications

J Nucl Med

(2013)

G. Segall et al.

SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0

J Nucl Med

(2010)

F.D. Grant et al.

Skeletal PET with 18F-fluoride: Applying new technology to an old tracer

J Nucl Med

(2008)

E. Even-Sapir et al.

The detection of bone metastases in patients with high-risk prostate cancer: ^99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, ¹⁸F-fluoride PET, and ¹⁸F-fluoride PET/CT

J Nucl Med

(2006)

M. Wondergem et al.

A literature review of ¹⁸F-fluoride PET/CT and ¹⁸F-choline or ¹¹C-choline PET/CT for detection of bone metastases in patients with prostate cancer

Nucl Med Commun

(2013)

K.A. Kurdziel et al.

The kinetics and reproducibility of ¹⁸F-sodium fluoride for oncology using current PET camera technology

J Nucl Med

(2012)

E.R. Dennis et al.

Bone scan index: A quantitative treatment response biomarker for castration-resistant metastatic prostate cancer

J Clin Oncol

(2012)

G. Cook et al.

¹⁸F-fluoride PET: Changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with ²²³Ra-chloride (Alpharadin)

EJNMMI Res

(2011)

K. Mertens et al.

PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature

Eur J Nucl Med Mol Imaging

(2010)

T. Hara et al.

Choline transporter as a novel target for molecular imaging of cancer

Mol Imaging

(2006)

T. Hara et al.

PET imaging of prostate cancer using carbon-11-choline

J Nucl Med

(1998)

FDA approves ¹¹C-choline for PET in prostate cancer

J Nucl Med

(2012)

L. Evangelista et al.

Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis

Clin Nucl Med

(2013)

G. Bauman et al.

(18)F-fluorocholine for prostate cancer imaging: A systematic review of the literature

Prostate Cancer Prostatic Dis

(2011)

Y. Yoshii et al.

Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: Uptake of radiolabeled acetate as a predictor of the targeted therapy outcome

PLoS One

(2013)

N. Oyama et al.

¹¹C-acetate PET imaging of prostate cancer

J Nucl Med

(2002)

N. Oyama et al.

¹¹C-acetate PET imaging of prostate cancer: Detection of recurrent disease at PSA relapse

J Nucl Med

(2003)

M. Beheshti et al.

Application of ¹¹C-acetate positron-emission tomography (PET) imaging in prostate cancer: Systematic review and meta-analysis of the literature

Br J Urol Int

(2013)

E. Mena et al.

¹¹C-Acetate PET/CT in localized prostate cancer: A study with MRI and histopathologic correlation

J Nucl Med

(2012)

M. Haseebuddin et al.

11C-acetate PET/CT before radical prostatectomy: nodal staging and treatment failure prediction

J Nucl Med

(2013)

H. Okudaira et al.

Putative transport mechanism and intracellular fate of trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic acid in human prostate cancer

J Nucl Med

(2011)

D.M. Schuster et al.

Initial experience with the radiotracer anti-1-amino-3-¹⁸F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma

J Nucl Med

(2007)

C. Nanni et al.

Comparison of ¹⁸F-FACBC and ¹¹C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: Preliminary results

Eur J Nucl Med Mol Imaging

(2013)

P.B. Zanzonico et al.

PET-based radiation dosimetry in man of ¹⁸F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer

J Nucl Med

(2004)

Cited by (27)

Feasibility of biology-guided radiotherapy for metastatic renal cell carcinoma driven by PSMA PET imaging
2023, Clinical and Translational Radiation Oncology
Biology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC.
All consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor.
Out of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT.
More than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.
Synthesis and in vitro proof-of-concept studies on bispecific iron oxide magnetic nanoparticles targeting PSMA and GRP receptors for PET/MR imaging of prostate cancer
2022, International Journal of Pharmaceutics
Citation Excerpt :
Prostate cancer (PCa) is a common malignancy for men, with high numbers of patients dying from the disease every year; however, early stage diagnosis through PSA (prostate specific antigen) testing and recent advances in therapeutic treatments have dramatically decreased the number of deaths (Siegel et al., 2020). PET (positron emission tomography) imaging of PCa is considered a valuable tool for early stage diagnosis, assessing sites of recurrent disease, guiding biopsy, staging and monitoring treatment response (Bouchelouche et al., 2011; Cho and Szabo, 2014; Evans et al., 2018; Regmi et al., 2021). Recently, multiparametric magnetic resonance imaging (MRI) has been established as a gold standard of local prostate imaging, while hybrid PET/MRI, which offers better soft tissue definition than CT, seems to be the promising future tool for diagnosis and staging of PCa (Mottet et al., 2021; Regmi et al., 2021).
Prostate cancer (PCa) is the most common malignancy worldwide in men. This is a proof-of-concept study describing the development of ⁶⁸Ga-magnetic iron oxide nanoparticles (mNP) targeting prostate specific membrane antigen (PSMA) and gastrin releasing peptide (GRPR) receptors as potential tools for diagnosis of PCa with PET/MRI. Two pharmacophores targeting PSMA, 1, and GRPR, 2, were coupled to mNPs carrying -SH (mNP-S1/2) or –NH₂ (mNP-N1/2) groups. The mNP-S1/2 and mNP-N1/2 were characterized for their size, zeta potential, structure, and efficiency of functionalization using dynamic light scattering (DLS), FT-IR and RP-HPLC. A direct ⁶⁸Ga-labelling procedure was followed, where ⁶⁸Ga-mNP-N1/2 proved superior to ⁶⁸Ga-mNP-S1/2 regarding radiolabelling efficiency, and thus were further evaluated in vitro. Toxicity studies in PCa cells (LNCaP, PC-3) showed low toxicity, and minimal hemolysis of red blood cells. In vitro assays in cells expressing PSMA (LNCaP), and GRPR (PC-3), showed specific time-dependent binding (40 min to plateau), high avidity (PC-3: K_d = 28.27 nM, LNCaP: K_d = 11.49 nM) and high internalization rates for ⁶⁸Ga-mNP-N1/2 in both cell lines.
Feasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour
2022, Clinical and Translational Radiation Oncology
Citation Excerpt :
Potential advantages of this technique include real-time tracking of a tumour, which can improve the accurate targeting of the tumour, and the ability to treat many tumours in a single session [11–14]. Prostate specific membrane antigen (PSMA) PET tracers are now available for imaging of primary and metastatic prostate cancer [15–20]. This imaging technique has demonstrated superior sensitivity and specificity for prostate cancer diagnosis compared to conventional imaging [21–23].
Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region.
Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV.
In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm³ to 148 cm³ (median = 52 cm³; IQR = 39 cm³ – 63 cm³). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 – 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm³; IQR = 4.5 cm³ – 20.0 cm³) and 50%SUVmax (median volume = 1.9 cm³; IQR = 1.1 cm³ – 3.8 cm³) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm.
It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.
PSMA PET and Radionuclide Therapy in Prostate Cancer
2016, Seminars in Nuclear Medicine
Citation Excerpt :
More recently, 18F-flouride PET/CT has been found to have improved sensitivity and specificity for sites of osseous metastatic involvement. Studies have demonstrated improved accuracy of 18F-Flouride PET/CT over MDP SPECT/CT in PCa.57-59 Increased fluoride uptake in malignant bone lesions reflects the increase in regional blood flow and bone turnover characterizing on bone metastases.
Prostate cancer (PCa) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of patients with PCa. Because no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. To optimize treatment outcome, especially in high-risk patients with PCa, therapy for PCa is moving rapidly toward personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate-specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, as it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guide focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low prostate-specific antigen values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa and is an area of active investigation. The “image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of patients with PCa and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy for PCa.
Evaluation of [18F]PFH PET renography to predict future disease progression in a rat model of autosomal dominant polycystic kidney disease
2016, Nuclear Medicine and Biology
Prognostic markers for progression of polycystic kidney disease (PKD) are limited. We evaluated the potential of early para-[¹⁸F]fluorohippurate ([¹⁸F]PFH) positron emission tomography (PET) renography to predict future progression of PKD in Han:SPRD rats with slowly progressive autosomal dominant PKD.
Male and female heterozygous (Cy/+) and normal littermate (+/+) Han:SPRD rats underwent [¹⁸F]PFH PET renography and blood sampling to measure serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations at 6 and 26 wk of age. T2 and T20 values, which represent the percent of the injected dose of [¹⁸F]PFH in kidneys at 2 and 20 min after injection, were determined from imaging data. T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at 26 wk of age, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression.
Male and female Cy/+ rats are known to manifest PKD of different severity, male Cy/+ rats display much more severe PKD than female rats. S-Cr and SUN concentrations did not differ between +/+ and Cy/+ rats and between female and male Cy/+ rats at 6 wk of age, but they were higher at 26 wk of age and male rats displayed higher values than female rats, which indicates inability of S-Cr and SUN to measure disease severity at an early stage. T20/T2 ratios were higher for Cy/+ than +/+ rats at 6 wk of age. Importantly, male Cy/+ rats displayed higher T20/T2 ratios than female Cy/+ rats. T20/T2 ratios obtained at 6 wk of age correlated well with S-Cr, SUN, and KW/BW% values obtained at 26 wk of age.
This study indicates that T20/T2 ratio derived from [¹⁸F]PFH PET renography at an early age could be useful as a novel prognostic marker to predict future disease severity in a rat model of ADPKD.
18F-fluoromethylcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: Which is better? A literature revision
2015, Nuclear Medicine and Biology
Citation Excerpt :
Radiolabeled-choline analogs are entrapped by PCa cells by choline transporters and are intracellularly phosphorylated by choline kinase (CK), which is strongly associated with phospholipid metabolism [1–4] (Fig. 1). Both 11C-choline and 18 F-radiolabeled-choline have been extensively used for imaging applications in PCa patients, mostly in Europe and Japan [5]; further growth has been recorded after the approval of production and use of 11C-choline for PET imaging in recurrent PCa by the US Food and Drug Administration, announced on September 2012 [6]. Current use of 11C-choline PET/CT in PCa patients has mainly been aimed at the early detection of disease recurrence, leading to a possible change in patient management.
The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of ¹⁸ F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC).
A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed.
FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC).
In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential.
FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed.

View all citing articles on Scopus

View full text

Molecular Imaging of Urogenital Diseases

Section snippets

Glucose Metabolism

Fluorocyclobutane-1-Carboxylic Acid

Fluoro-5α-Dihydrotestosterone

Prostate-Specific-Membrane Antigen

Glucose Metabolism

Molecular Biology

Bladder Cancer

Mayo Clin Proc

Urology

Urology

Commun

Nucl Med Biol

Semin Nucl Med

Nucl Med Biol

Eur Urol

Eur Urol

Eur J Radiol

Lancet

Urology

Urology

Urology

Human Pathol

Urol Oncol

J Urol

J Vasc Interv Radiol

Cancer statistics, 2010

CA Cancer J Clin

Unmet needs in the prediction and detection of metastases in prostate cancer

Oncologist

The changing therapeutic landscape of castration-resistant prostate cancer

Nat Rev Clin Oncol

Optimizing outcomes of advanced prostate cancer: Drug sequencing and novel therapeutic approaches

Oncology (Williston Park)

Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy

Eur Urol

2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy

Clin Cancer Res

Fluorodeoxyglucose positron emission tomography as an outcome measure for castrate metastatic prostate cancer treated with antimicrotubule chemotherapy

Clin Cancer Res

Prognostic value of baseline [18F] fluorodeoxyglucose positron emission tomography and 99mTc-MDP bone scan in progressing metastatic prostate cancer

Clin Cancer Res

Dynamic bone imaging with 99mTc-labeled diphosphonates and 18F-NaF: Mechanisms and applications

J Nucl Med

SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0

J Nucl Med

Skeletal PET with 18F-fluoride: Applying new technology to an old tracer

J Nucl Med

The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT

J Nucl Med

A literature review of 18F-fluoride PET/CT and 18F-choline or 11C-choline PET/CT for detection of bone metastases in patients with prostate cancer

Nucl Med Commun

The kinetics and reproducibility of 18F-sodium fluoride for oncology using current PET camera technology

J Nucl Med

Bone scan index: A quantitative treatment response biomarker for castration-resistant metastatic prostate cancer

J Clin Oncol

18F-fluoride PET: Changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with 223Ra-chloride (Alpharadin)

EJNMMI Res

PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature

Eur J Nucl Med Mol Imaging

Choline transporter as a novel target for molecular imaging of cancer

Mol Imaging

PET imaging of prostate cancer using carbon-11-choline

J Nucl Med

FDA approves 11C-choline for PET in prostate cancer

J Nucl Med

Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis

Clin Nucl Med

(18)F-fluorocholine for prostate cancer imaging: A systematic review of the literature

Prostate Cancer Prostatic Dis

Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: Uptake of radiolabeled acetate as a predictor of the targeted therapy outcome

PLoS One

11C-acetate PET imaging of prostate cancer

J Nucl Med

11C-acetate PET imaging of prostate cancer: Detection of recurrent disease at PSA relapse

J Nucl Med

Application of 11C-acetate positron-emission tomography (PET) imaging in prostate cancer: Systematic review and meta-analysis of the literature

Br J Urol Int

11C-Acetate PET/CT in localized prostate cancer: A study with MRI and histopathologic correlation

Prognostic value of baseline [18F] fluorodeoxyglucose positron emission tomography and ^99mTc-MDP bone scan in progressing metastatic prostate cancer

Dynamic bone imaging with ^99mTc-labeled diphosphonates and 18F-NaF: Mechanisms and applications

The detection of bone metastases in patients with high-risk prostate cancer: ^99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, ¹⁸F-fluoride PET, and ¹⁸F-fluoride PET/CT

A literature review of ¹⁸F-fluoride PET/CT and ¹⁸F-choline or ¹¹C-choline PET/CT for detection of bone metastases in patients with prostate cancer

The kinetics and reproducibility of ¹⁸F-sodium fluoride for oncology using current PET camera technology

¹⁸F-fluoride PET: Changes in uptake as a method to assess response in bone metastases from castrate-resistant prostate cancer patients treated with ²²³Ra-chloride (Alpharadin)

FDA approves ¹¹C-choline for PET in prostate cancer

¹¹C-acetate PET imaging of prostate cancer

¹¹C-acetate PET imaging of prostate cancer: Detection of recurrent disease at PSA relapse

Application of ¹¹C-acetate positron-emission tomography (PET) imaging in prostate cancer: Systematic review and meta-analysis of the literature

¹¹C-Acetate PET/CT in localized prostate cancer: A study with MRI and histopathologic correlation

Putative transport mechanism and intracellular fate of trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic acid in human prostate cancer

Initial experience with the radiotracer anti-1-amino-3-¹⁸F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma

Comparison of ¹⁸F-FACBC and ¹¹C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: Preliminary results

PET-based radiation dosimetry in man of ¹⁸F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer