Amino Acid Transport Imaging of Parathyroid Adenomas With Anti-3-[18F]FACBC
Phase: NA
Conditions: Parathyroid Disease
Sponsor: David M. Schuster, MD

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IRB00051415 
NCT01574287 
Protocol 
Amino Acid Transport Imaging of Parathyroid Adenomas with anti-3-[18F] FACBC 
Principal Investigator: David M Schuster, M.D. 
Date: 11/22/2013 
 

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Amino Acid Transport Imaging of Parathyroid Adenomas with anti-3-[18F]FACBC 
 
David M Schuster, M.D. 
Emory University  
Department of Radiology and Imaging Sciences 
Emory University School of Medicine, Atlanta, GA 
Phone:  (404) 712-4859 
email: dschust@emory.edu 
 
 
Rianot Amzat, MD 
Pooneh Taleghani, MD 
Mark M Goodman, MD 
Raghu Halkar, MD 
Collin Weber, MD 
Jyotirmay Sharma, MD 
Dr. Susan Safley 
Francois Villinger, DVM, PhD 
Weiping Yu, PhD 
Carlos Moreno, PhD 
Cynthia Cohen, MD 

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Schema: 
 
 
 
 
 
 
Patient recruitment per inclusion criteria (n=12) 
All patients undergo standard of care preoperative imaging 
including 99mTc MIBI dual phase SPECT-CT 
 (6 of each low and high MIBI uptake) 
anti-3-[18F]FACBC 
PET-CT (n=6, low 
uptake MIBI) 
Correlation to 99mTc MIBI dual phase SPECT-CT 
and validation to truth as established by routine surgery and histology 
anti-3-[18F]FACBC 
PET-CT (n=6, high 
uptake MIBI) 

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Precis/Abstract: 
 
Hyperparathyroidism is an increasingly significant medical and public health condition. The most 
common technique for preoperative localization is a SPECT/CT, utilizing Tc-99m-sestamibi as a 
radiotracer.  However, the reported sensitivity and specificity is only 80%. Thus there is a need 
for more accurate preoperative localization of parathyroid adenomas. Anti-1-amino-3-
[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) is a synthetic amino acid analog for 
positron emission tomography (PET) which has demonstrated promise for the staging and 
restaging of carcinoma. There is some preliminary evidence that amino acid transport may be 
upregulated in parathyroid adenomas and hyperplasia. We plan to perform a pilot study in 12 
patients who are scheduled for surgery after standard preoperative evaluation for biochemically 
confirmed hyperparathyroidism. Patients will undergo anti-3-[18F]FACBC PET-CT. 6 each in 
high group will have had low or high uptake of MIBI. Uptake within proven disease will be 
measured for the amino acid PET radiotracer, compared against current imaging standard 
exams such as dual phase sestamibi SPECT-CT, and validated to truth by surgery and 
histologic proof. Results of this pilot study will be used to possibly design larger and more 
comprehensive studies examining clinical utility. 

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A. Introduction and Background: 
 
Hyperparathyroidism is an increasingly significant medical and public health condition.  In the 
past two decades, the incidence of hyperparathyroidism has increased 300%, and currently the 
disease affects at least 30,000 new patients each year in the United States.  Parathyroid 
adenomas, parathyroid hyperplasia in primary and secondary hyperparathyroidism, and 
parathyroid carcinomas all are increasing in frequency. Primary hyperparathyroidism is seen in 
one out of 500-1000 people and is caused by a single adenoma in 85% of cases (1).  The 
mechanisms responsible for the increased incidence of hyperparathyroidism are not known.  
Environmental factors such as ionizing radiation exposure have been suggested by some 
authorities.  Multiple organs are affected in patients with hyperparathyroidism; notably, a 
worsening of the severity of osteoporosis and accelerated arteriosclerotic disease and 
hypertension.  Parathyroid carcinoma no longer is a rare illness.  There is no effective oncologic 
therapy for parathyroid carcinoma, and it is often fatal.   
 
 
Surgery is the only effective management for primary hyperparathyroidism.  Preoperative 
localization of the adenoma allows unilateral neck exploration for removal of the tumor (2, 3).  
Since this approach decreases duration of surgery and morbidity, preoperative localization is 
gaining more importance.  However, pre-operative and intra-operative parathyroid tumor 
localization can be challenging, in part because current imaging methodologies are sub-optimal, 
failing to identify the parathyroid tumor in as many as 30% of patients (4).  In reoperative 
parathyroidectomy for persistent or recurrent hyperparathyroidism, localization plays an even 
greater role (5). Unfortunately current multiple imaging modalities fail to localize 10-15% these 
of tumors.   
 
The most common technique for preoperative localization is a SPECT/CT, utilizing Tc-99m-
sestamibi (MIBI) as a radiotracer. 99mTc MIBI early and delayed (dual phase) imaging with 
Single Photon Emission Computerized Tomography (SPECT) or SPECT/CT has become the 
standard of care (4). 99mTc MIBI is an isonitrile compound which tends to accumulate in 
mitochondria and has a short half life of 6 hours, physical characteristics ideally suited for 
imaging with a Gamma camera.  99mTc MIBI concentrates both in thyroid and parathyroid tissues 
but washes out faster from thyroid tissue than parathyroid tumors, allowing dual phase imaging 
to localize the parathyroid tumors (6). SPECT imaging improves the contrast and facilitates 
location of  the parathyroid tumors, while SPECT/CT provides three-dimensional localization (7).  
However, the reported sensitivity and specificity is only 80% (4, 8). Parathyroid glands usually 
are located close to the thyroid and 99mTc MIBI concentrates both in thyroid and parathyroid 
tissue. Hence there is a need for a tracer/imaging tool that concentrates in the parathyroid but 
not in the thyroid.  
A more sensitive and specific radiotracer/tracking agent would markedly improve our ability to 
identify parathyroid tumors preoperatively, and thus offer more patients a minimally invasive 
parathyroidectomy. 

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Amino acids are involved in many aspects of human nutrition including the synthesis of proteins. 
Amino acid metabolism has been demonstrated to be upregulated  in many tumors including 
prostate carcinoma (9). A number of amino acid radiotracers have been utilized to study 
carcinoma and other tumors including naturally occurring L-[11C]methionine, L-3-[123I]iodo-
alpha-methyl tyrosine (IMT),  and L-[1-11C]5-hydroxytryptophan (5-HTP). Anti-1-amino-3-
[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) is a non-natural amino acid analog 
with low renal excretion and high pancreatic concentration. In some manner it may be 
transported similar to the amino acid leucine. anti-3-[18F]FACBC  has demonstrated promise for 
the staging and restaging of prostate carcinoma (10) and has demonstrated utility for cerebral 
neoplasia (11). anti-3-[18F]FACBC biodistribution studies demonstrate that radiotracer 
concentration in the thyroid is less than that in the muscle (12).  
Parathormone is a 
peptide hormone, and 
the bioactive 
conformation includes a 
long helical dimer 
containing 10 Leucine 
residues. Our initial 
work with anti-3-
[18F]FACBC in primary 
cultures of human 
parathyroid cells (Figure 
1) have shown 
significant specific 
uptake of anti-3-
[18F]FACBC by these 
parathyroid cells.  anti-
3-[18F]FACBC 
incorporation in 
parathyroid tumor cells in vitro was assayed by gamma counting.  Specific uptake of anti-3-
[18F]FACBC, an L-leucine analog, was shown by blocking with an L-type transporter inhibitor 
(BCH) and a multiple amino acid inhibitor (ACS), while an A-type inhibitor (MeAIB) did not block 
uptake. Hence we hypothesize that parathyroid cells will concentrate anti-3-[18F]FACBC, and 
thus anti-3-[18F]FACBC can be used as a tracer for positron emission imaging. 
 
Figure 2 is an example of the biodistribution patterns of anti-3-[18F]FACBC, but with no 
significant normal uptake within thyroid. We will perform a pilot study of this amino acid 
analogue radiotracer to determine if there is sufficient uptake within parathyroid adenomas to 
necessitate a larger study of clinical utility.  
 
In addition, we have constructed a microarray examining genetic expression of amino acid 
transporters (AAT) via RT-PCR analysis, to determine which amino acid transporters may be 
responsible for anti-3-[18F]FACBC uptake within parathyroid adenomas, if any. If imaging results 
Fig 1 

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are promising, we will utilize this microarray on the adenoma tissue obtained from surgical 
excision. This will be followed by IHC analysis using antibodies to prime AAT candidates to 
confirm phenotypic expression.  
 
 
Figure 2: 
 
anti-3-[18F]FACBC PET at approximately 30 minutes 
demonstrating the normal biodistribution pattern but with no 
significant normal thyroid uptake.  
 
 
 
 
 
 
 
 
 
 
B. Objectives 
 
Accurate preoperative identification of parathyroid adenomas is critical in enabling appropriate 
minimally invasive surgery and in identifying ectopic adenomas that would necessitate a change 
in surgical approach.  
 
Our overarching goal is to establish if amino acid analogue imaging with the positron emission 
tomographic radiotracer anti-3-[18F]FACBC demonstrates sufficient uptake within parathyroid 
adenomas to make a more comprehensive study worthwhile. Future studies may be directed at 
a larger clinical trial. In addition, we will examine the proteomics of amino acid transport 
mechanism via gene array, RT-PCR, as well as immunohistochemistry of resected adenoma 
tissue to help determine the mechanism of uptake of anti-3-[18F]FACBC PET-CT, and to 
correlate with Sestamibi positive or negative status.  
 
The primary aim of this study is to determine if anti-3-[18F]FACBC PET-CT demonstrates uptake 
within parathyroid adenomas and to understand time-activity studies in a dynamic manner to 
record preliminary data of uptake kinetics if present.  
 
 
Specific Aims 
 
Specific Aim 1. To evaluate the presence or absence of uptake of anti-3-[18F]FACBC in 
parathyroid adenomas and uptake kinetics if present, and if this uptake varies with sestamibi 
avidity of the adenomas.  
 
Specific Aim 2. To evaluate uptake mechanisms and specific amino acid transporter regulation 
of anti-3-[18F]FACBC in parathyroid adenomas. 

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Rationale. As has been outlined in Section A of the proposal, current imaging techniques in the 
preoperative identification and localization are good, but not ideal. More accurate techniques 
are required to better select patients for minimally invasive surgery. Parathormone is a peptide 
hormone containing 10 Leucine residues. We have developed an amino acid analogue PET 
radiotracer at Emory which may exploit amino acid transport mechanisms in parathormone 
receptor activation or via upregulation of amino acid transport in parathyroid adenomas and 
hyperplasia compared to normal parathyroid tissue. Our initial work with anti-3-[18F]FACBC in 
primary cultures of human parathyroid cells (Figure 1) has shown significant specific uptake of 
anti-3-[18F]FACBC by these parathyroid cells.   
 
The specific hypothesis in this proposal is that amino acid transport in parathyroid adenoma and 
hyperplasia is upregulated compared with normal parathyroid tissue and that this elevated 
uptake can be exploited for lesion identification by use of PET amino acid radiotracer imaging. 
The most comprehensive manner to assess our hypothesis is to undertake a prospective pilot 
study in patients with biochemical evidence of primary hyperparathyroidism and who are 
scheduled for standard of care surgery and typical preoperative clinical imaging including 99mTc 
MIBI SPECT-CT.  
 
We propose assembling a dedicated multidisciplinary team of experts in amino acid radiotracer 
synthesis and imaging as well as surgical therapy of hyperparathyroidism. Outcomes will be 
validated by direct comparison to truth as established by histology and surgical findings. We will 
also in Specific Aim 2, examine potential mechanisms of uptake via gene array, RT-PCR 
analysis and immunohistochemical techniques. 
 
C. Study design and methods 
 
Experimental design. We will undertake a study with 12 patients who have biochemical and 
clinical evidence of primary hyperparathyroidism and who are scheduled for routine surgery and 
preoperative imaging. The patients will serve as their own control. This study will not interfere 
with standard patient evaluation or delay therapy. Patients will receive one additional study 
using the amino acid analogue with anti-3-[18F]FACBC. Within the group of 12, we will choose 6 
patients with low MIBI uptake and 6 with high uptake since amino acid uptake could also vary in 
each sub-population. Dynamic imaging will be performed for 60 minutes. 
 
All patients will undergo routine preoperative imaging including dual phase 99mTc sestamibi 
scanning and other imaging as appropriate such as ultrasound, MRI, and/or contrast enhanced 
CT scanning. 
 
We will investigate amino acid transport kinetics and conspicuity within parathyroid adenomas 
utilizing anti-3-[18F]FACBC PET-CT (Specific Aim #1). We will compare various uptake 
parameters to that of standard of care imaging with dual phase 99mTc sestamibi SPECT-CT and 
validate to truth via surgery and histologic analysis. Resected tissue will also undergo gene 

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array, RT-PCR analysis and immunohistochemistry as appropriate to investigate amino acid 
transport mechanism and other factors in uptake (Specific Aim #2). 
C.1 anti-3-[18F]FACBC Radiolabeling 
Methods. We will prepare anti-3-[18F]FACBC by the automated synthesis developed by J. 
McConathy and M.M. Goodman (13) as outlined in Figure 3. The automated radiosynthesis of 
anti-3-[18F]FACBC will be carried out in a chemical process control unit (CPCU) with a computer 
interface. The two-step reaction sequence will involve incorporation of no-carrier-added 
potassium [18F]fluoride into a protected triflate precursor and deprotection using aqueous 
hydrochloric acid. The crude reaction mix will be passed in series through ion-retardation resin, 
an alumina-N SepPak®, an HLB cartridge and a 0.22 µm sterile filter, and the resulting aqueous 
solution will be collected in a dose vial. The radiochemical purity of the product will be 
determined by TLC.  Additional chemical solvent purity will be measured by Gas 
Chromatography (GC). The total time for synthesis of anti-3-[18F]FACBC after delivery of 
18[F]fluoride will be ~70 minutes, and the average decay-corrected yield of anti-3-[18F]FACBC 
will be 24 ± 4 % (n = 40 runs, average ± standard error) in over 99% radiochemical purity . This 
procedure will provide 140-200 mCi of anti-[18F]FACBC at the end of synthesis. We have 
prepared greater than 30 batch productions for tumor imaging in volunteer subjects. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
C.2 PET-CT imaging protocol  
PET-CT images will be acquired on a GE Discovery DLS (8 slice), DST (16 slice), MV600 (16 
slice), MV690 (16 Slice) or similar PET-CT scanner as described in the literature (14).  Quality 
control scans are performed every morning and the scanner is calibrated by scanning uniform 
phantoms with the same activity concentration and protocols as used in the various 
experiments.  All studies will use measured attenuation correction (routinely acquired through 
the initial CT portion of the scan).  Dead time, detector efficiency and scatter corrections will be 
applied using the routines supplied by the manufacturer. The resulting images will be 
quantitatively calibrated and have 6 mm isotropic resolution.   
 
All subjects will initially be required to fast for four hours to normalize their neutral amino 
acid levels. The study will typically take place in the afternoon. Oral or IV contrast will not be 
used for this study. Prior to placement in the tomographic gantry, an intravenous catheter will be 
placed for injection of tracer. The subject will be placed in the tomographic gantry for completion 
of the CT scan utilizing standard acquisition parameters of approximately 80-120 mA to be 
utilized for anatomic imaging and correction of emission data (approximately 1 minute). anti-3-
[18F]FACBC (10 mCi) will be injected into an antecubital vein in a slow bolus infusion over 1-2 
minutes. Subsequently, 2-3 consecutive 2-4 minute per bed position (depending on scanner 
BocHN
CO2CH3
OSO2CF3
BocHN
CO2CH3
18F
H2N
CO2H
18F
a
b
anti-[18F]FACBC
a)K18F, K222, K2CO3; 90C b) 4 NHCl, 120 C
Figure 3. Synthesis 
of anti-FACBC 
 

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type and patient body habitus) will be obtained of the neck then chest to the anterior border of 
the heart for one hour.  
 
Summary of PET-CT Scanning Procedure 
1) The patient will be placed in the tomographic gantry for a CT scan of the chest (80-120 mA) 
to be utilized for anatomic imaging and correction of emission data (approximately 1 minute).  
2) The patient will then receive a bolus of anti-3-[18F]FACBC injected IV over 1-2 minutes 
3) The dosage will be approximately 10.0 mCi (370 MBq). 
4) A 2-4 minute per bed position PET acquisition will start at the neck with the inferior aspect of 
the acquisition to include the anterior border of the heart.  
5) 2-3 bed positions will be obtained which should cover the neck through the anterior border of 
the heart.  
6) This sequence will be repeated for 60 minutes of dynamic imaging. 
7) The entire study including injection of radiotracer should take approximately 60 minutes. 
 
C.4 Image Analysis of anti-[18F]FACBC PET-CT 
Methods. The methods of image analysis to be used for the anti-3-[18F]FACBC PET-CT are as 
follows: 
1) Images will be reconstructed with iterative technique and hardware fused (PET to CT) on a 
GE AW or MimVista workstation which enables SUV (mean, maximum) as well as standard size 
measurements of lesions. Whenever possible we will use 3 dimensional PET-Edge 
conformational regions of interest (ROI) to encompass the entire structure under question such 
as a lymph node or prostate bed.  
2) Visual inspection of the PET-CT images in separate sessions by a board certified nuclear 
medicine physicians/nuclear radiologist will take place with calculation of SUVmax, SUVmean, 
total lesion activity of target lesions within parathyroid lesions (either at typical location posterior 
to the thyroid or in well described ectopic locations including the mediastinum). In addition, we 
will derive similar measurements of background structures from key organs including thyroid, 
muscle (pectoralis muscle), bone marrow (T5), and blood pool (aorta at arch). Tumor to 
background values will also be calculated. All measurements will take place over multiple time 
periods, including but not limited to 15min, 30 min, 45 min and 60 min in order to also calculate 
retention indices of tracer. More formal time-activity curves will also be constructed on separate 
specialized platforms. 
3) Subsequent to analysis of the FACBC PET images, results of dual phase sestamibi study will 
be unblinded to the original reader and results correlated to sestamibi imaging as well as other 
imaging that may have been acquired such as ultrasound, MR, and/or contrast CT of the neck.  
 
C.5 Comparison to “Truth” 
Results of the amino acid PET imaging will be measured against surgical findings and histologic 
proof. Both size of adenoma, cellular density, as well as other pathologic criteria will be 
correlated to various uptake parameters described above. 
 

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C.6 Followup 
Success of surgery (and thus confirmation that all adenomas or hyperplasia have been 
resected) will be by usual clinical means resulting in normalization of intraoperative and/or post-
operative PTH levels. But this will be done as part of routine standard of care without special 
visits required of the patient. 
 
C.7 Tissue analysis 
Resected tissue will be analyzed in reference to amino acid transporter characteristics with well-
established RT-PCR techniques and immunohistochemistry in current use by this group on 
related projects. Briefly, we have constructed a genotypic microarray for amino acid 
transporters. These include but are not limited to: LAT1, LAT2, LAT3, ASCT1, ASCT2, BAT1, 
PAT1, xCT, yLAT1, and yLAT2. Tissue will be microdissected from the adenoma and normal 
parathyroid tissue and sent for analysis. If we determine overexpression of candidate AAT, the 
samples will then undergo IHC analysis utilizing commercially available antibodies to candidate 
transporters. In addition, depending on imaging and preliminary analysis, resected samples may 
undergo more generic gene array (DASL) and other IHC analyses to better understand biologic 
mechanisms involved with and correlating to varying degrees of anti-3-[18F]FACBC and 
Sestamibi uptake. 
 
D. Participant Selection: 
 
Methods.  
 
All patients will be recruited from Emory Healthcare Parathyroid Surgery clinics per the inclusion 
and exclusion criteria below.  
 
Written informed consent will be obtained before subject participation in the study.  No 
procedures will be performed before written informed consent is obtained.  Participants will be 
assigned an identification number for screening purposes; data collected during the screening 
process will be recorded using that number.   
 
PET Scan Day:  The following procedures will be performed: 
 
Obtain written informed consent 
 
Inclusion/exclusion criteria review 
 
Vital signs measurements 
 
Medication history review 
 
Clinical laboratory tests (serum chemistries, CBC and urinalysis) 
 
To be repeated within one week after scan 
Pregnancy based on serum or urine pregnancy test obtained within 24 hours prior to injection of 
radiotracer imaging prior to injection of radiotracer (for women of childbearing potential per 
Radiology Department clinical guidelines)  
 
 

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Inclusion Criteria:  
 
1. Patients must be 18 years of age or older. 
 
2. Patients will have biochemical and/or clinical evidence of primary hyperparathyroidism and be 
a surgical candidate for definitive parathyroid surgery . 
 
3. Ability to lie still for PET scanning 
 
4. Patients must be able to provide written informed consent 
 
 
Exclusion Criteria: 
 
1. Age less than 18. 
 
2. Inability to lie still for PET scanning. 
 
3. Cannot provide written informed consent. 
 
4. History of secondary hyperparathyroidism. 
 
5. Positive serum or urine pregnancy test within 24 hours of imaging prior to injection of 
radiotracer (for women of childbearing potential per Radiology Department clinical guidelines)  
 
  
E. Statistical Analysis.  
 
Since this is a pilot study only descriptive statistics will be possible.  
 
F. Adverse Event Reporting 
 
Any patient death that may be due to the study procedure (i.e. severe radiotracer reaction), 
unanticipated problem, or protocol deviation/non-compliance would be promptly reported to the 
Emory IRB office.  Additionally any patient death not associated with the study procedure or 
serious anticipated event (i.e. radiotracer allergy) will be reported to the Emory IRB and FDA 
upon continuing review. This radiotracer is studied under IND 72437 and monitoring will be 
performed per already agreed upon FDA guidance. Over 100 patients have been studied 
without adverse events. 
G. Data and Safety Monitoring Plan (DSMP): 
Patients will be monitored by the technologists and study nurse before and after the studies for 
any adverse events/reactions.  They will be given contact phone numbers to call if they 
experience any problems (i.e. problems with the IV site, any allergic reaction symptoms).  They 
will be followed routinely by their referring surgeon with clinical exams, and the PI will work with 

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the co-investigators and referring physicians to ensure that the patients continue to follow up as 
scheduled. 
In addition, a DSMB who will consist of Drs. Weber, Galt, Schuster, Halkar, and Sharma will 
meet formally if an adverse event has been reported.  Any serious adverse events (see above) 
will be communicated by the PI to the Emory IRB using standard adverse event reporting forms.  
 
H: Pharmaceutical, biologic, and device information 
 
Radiation Dosimetry. The study will be approved by not only the Emory IRB but also the 
Radiation Safety Committee. The maximum number of PET studies a patient will receive in this 
protocol is 1 FACBC study. 
 
Depending on the distribution of the radionuclide in the body, the whole body dose may not be 
the critical factor in single or longitudinal studies. It is also of interest to know which organ 
receives the highest absorbed dose. This organ is referred to as the critical organ. Often the 
limit for an individual organ dose is reached before the limit established for the whole-body. The 
United States Food and Drug Administration in Title 21 CFR Part 361 limits the whole body 
radiation dose to adult research subjects to less than 3 rem (30 mSv) for a single injection and 5 
rem (50 mSv) effective dose equivalent (EDE) annually. A single organ cannot receive more 
than 5 rem (50mSv) in a single injection and 15 rem (150 mSv) effective dose equivalent 
annually. These constraints on dose will limit the maximum number of injections for research 
subjects. The studies proposed in this application fall within these guidelines. 
 
Whole-body human biodistribution studies of FACBC show that it is retained in liver and 
pancreas. A 10 mCi (370 MBq) injection of FACBC results in a whole-body effective dose 
equivalent of 0.52 rem (5.2 mSv) and a critical organ absorbed dose of 1.9  rad (19.3 mGy) to 
liver (12). 
 
The level of radiation for the PET scan is the same as received in widely used diagnostic 
studies such as the currently used 18F-FDG and is equal to or less than 20 percent of the 
amount allowed a radiation worker in a year (5 rem). The calculated whole body exposure to the 
individual will be less than 0.5 rem for each PET scan. Radiation exposure for the transmission 
images on the PET-CT is comparable to a routine CT scan, which is .5 rem at 80-120 mA for 
the limited body area covered (chest only).  
 
The radiotracer used in this study is governed by FDA IND 72437 and is subject to agreed upon 
safety monitoring by the FDA, a copy of which is on file with the IND holder, Dr. David Schuster. 

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3. 
Coakley AJ, Kettle AG, Wells CP, O'Doherty MJ, Collins RE. 99Tcm sestamibi--a new agent for 
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Ishibashi M, Nishida H, Hiromatsu Y, Kojima K, Uchida M, Hayabuchi N. Localization of ectopic 
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Ishibashi M, Nishida H, Hiromatsu Y, Kojima K, Tabuchi E, Hayabuchi N. Comparison of 
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7. 
Zeng W, Sepulveda JN, Nye J, et al. Posterior bladder layering of excreted 18F-FDG on PET/CT. 
Nucl Med Commun. 2010;31(10):859-63. 
8. 
Schreibmann E, Nye JA, Schuster DM, Martin DR, Votaw J, Fox T. MR-based attenuation 
correction for hybrid PET-MR brain imaging systems using deformable image registration. Med Phys. 
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9. 
Sakata T, Ferdous G, Tsuruta T, et al. L-type amino-acid transporter 1 as a novel biomarker for 
high-grade malignancy in prostate cancer. Pathol Int. 2009;59(1):7-18. 
10. 
Schuster DM, Votaw JR, Nieh PT, 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;48(1):56-
63. 
11. 
Schuster DM, Votaw JR, Halkar RK, et al. Uptake of the Synthetic PET Amino Acid Radiotracer 1-
Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (18F-FACBC) Within Primary and Metastic Brain 
Cancer Compared with 18F-Fluorodeoxyglucose (18F-FDG). J Nucl Med. 2003;5:167p. 
12. 
Nye JA, Schuster DM, Yu W, Camp VM, Goodman MM, Votaw JR. Biodistribution and Radiation 
Dosimetry of the Synthetic Nonmetabolized Amino Acid Analogue Anti-18F-FACBC in Humans. J Nucl 
Med. 2007. 
13. 
McConathy J, Voll RJ, Yu W, Crowe RJ, Goodman MM. Improved synthesis of anti-[18F]FACBC: 
improved preparation of labeling precursor and automated radiosynthesis. Appl Radiat Isot. 
2003;58(6):657-66. 
14. 
Schuster DM, Savir-Baruch B, Nieh PT, et al. Report of a clinical trial of anti 1 amino 3 
[18F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) PET-CT in recurrent prostate carcinoma. J 
Nucl Med. 2010;51 (Suppl. 2):127P.