11C-Methionine and 2-18F-Fluoro-2-Deoxy-D-Glucose PET Imaging in Patients With Progressive Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: Memorial Sloan Kettering Cancer Center

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Amended: 4/10/07 
Page 1 of 16 
 
 
 
11C-METHIONINE, 2-[18F]-FLUORO-2-DEOXY-D-GLUCOSE, AND [18F] 
DIHYDROTESTOSTERONE (FDHT) PET IMAGING IN PATIENTS WITH PROGRESSIVE 
PROSTATE CANCER 
 
 
1.0 
PROTOCOL SUMMARY: 
3 
2.0 
OBJECTIVES: 
3 
3.0 
RATIONALE AND BACKGROUND 
4 
3.1 
DISEASE INFORMATION 
4 
3.2 
CONVENTIONAL IMAGING MODALITIES 
5 
3.3 
POSITRON EMISSION TOMOGRAPHY 
5 
3.4 
EQUIPMENT INFORMATION (PET) 
7 
3.5 
STANDARD EVALUATION SCHEMA 
7 
4.0 
BACKGROUND DRUG INFORMATION 
8 
5.0 
PATIENT ELIGIBILITY 
8 
6.0 
PRETREATMENT EVALUATION 
9 
7.0 
TREATMENT PLAN 
9 
8.0 
TOXICITY ASSESSMENT AND MANAGEMENT 
11 
9.0 
GUIDELINES FOR REPORTING ADVERSE DRUG REACTIONS 
11 
10.0 CRITERIA FOR REMOVAL FROM STUDY 
11 
11.0 DATA ANALYSIS 
12 
12.0 BIOSTATISTICAL CONSIDERATIONS 
12 
13.0 SUBJECT REGISTRATION 
13 
14.0 PROTECTION OF HUMAN SUBJECTS 
13 
15.0 INFORMED CONSENT PROCEDURES 
14 
16.0. BIBLIOGRAPHY 
Z15 
 
 
STUDY COORDINATORS: 
 
Steven M. Larson, M.D. 
(212) 639-7373 
Michael J. Morris, M.D. (*) 
(212) 639-5132 
Mentor: Howard I. Scher, MD(*) 
(212) 639-2364 

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DEPARTMENT OF DIAGNOSTIC RADIOLOGY: 
 
Nuclear 
Medicine/Cylotron : 
Tim Akhurst, MD, Henry Yeung, MD, Ronald D. Finn, PhD, Heiko Schoder, 
MD 
 
Medical Imaging: 
Larry Schwartz, MD. 
DEPARTMENT OF MEDICAL PHYSICS: 
John Humm, PhD, Yusef Erdi, PhD 
 
GENITOURINARY ONCOLOGY SERVICE, DEPARTMENT OF MEDICINE: 
 
Howard I. Scher, MD,* Susan Slovin, MD,PhD*; Christine Liebertz, RN;   Tracy Curley, RN; Robert 
Motzer, MD; Dean Bajorin, MD; Lou Kampel, MD; Jason Koutcher, MD,PhD. 
 
DIVISION OF HEMATOLOGIC ONCOLOGY: 
 
David Golde, MD. 
 
DEPARTMENT OF BIOSTATISTICS AND EPIDEMIOLOGY: 
 
Glen Heller, Ph.D. 
 
DEPARTMENT OF CLINICAL CHEMISTRY: 
 
Morton Schwartz, PhD. 
CLINICAL TRIALS OFFICE: 
Karen Siedlecki 
 
(*) designated to obtain informed consent 
 
MEMORIAL SLOAN-KETTERING CANCER CENTER 
1275 York Avenue 
New York, NY 10021 
(212) 639-2364 

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Amended: 4/10/07 
Page 3 of 16 
 
 
 
1.0 
PROTOCOL SUMMARY: 
The imaging modalities used to monitor prostate cancer in man are limited. The disease typically 
spreads to osseous sites, where changes are difficult to quantitate on a serial basis. The proposed 
trial is the first in a series of studies designed to evaluate the biology of prostate cancer in vivo 
using PET imaging. It is based on the ability of positron emitting radiopharmaceuticals to serve as 
tracers of biologic events. In this study, we will examine the metabolic properties of 11C- 
methionine and FDG in prostate cancer by PET imaging. 
 
Initially, we will define the degree of correlation between FDG or C-11-methionine and standard 
imaging modalities such as CT/MRI and bone scans. We have observed discordance between 
uptake of [11C]-methionine (CMET) and FDG in individual sites.(1) Pilot studies have given us a 
basis for estimates of variability and differences between FDG and CMET, and kinetic data has 
led to the design of acquisition protocols that make whole body PET imaging of CMET practical 
in patients. As such, we will continue to compare on a site by site basis the uptake of 11C- 
methionine 
and 
FDG 
by 
performing 
whole 
body 
PET 
imaging 
following 
each 
radiopharmaceutical administration. Comparisons will be made to bone scintigraphy using 99m- 
Tc scanning, computed tomography, and, when clinically indicated, magnetic resonance imaging 
to assess whether sites detected by PET imaging are identified using standard imaging techniques 
and vice versa. Also, where tumor sites are identified on PET scans, a semiquantitative index, the 
standardized uptake value (SUV), as well as related parameters of total lesion metabolism (TLM) 
will be calculated as an objective measurement. In selected patients, imaging will be performed 
with F-18 fluoro dihydrotestosterone (FDHT), obtained through a collaboration with Michael 
Welch, Ph.D. of Washington University, St. Louis.(2) 
 
We will also define the utility of PET as an outcome measure following treatment by assessing 
the effects of treatment on SUV. Selected patients will be asked to undergo follow-up PET 
scanning along with follow-up bone scintigraphy, CT or MRI, where clinically appropriate. 
 
All patients with histologically documented progressive prostate cancer are eligible, including 
those with localized disease, rising PSA, non-castrate metastatic, and castrate metastatic disease. 
Progression may be defined either by a rise in PSA of > 50%, development of new bone lesions 
or an increase in pre-existing lesions, or an increase in measurable disease. 
 
Patients will undergo PET scanning using either FDG either alone or with CMET or DHT 
(performed the day following the FDG scan). Serum will be drawn to define the 
pharmacokinetic properties of the tracer. Serial PET scans will be performed at baseline, four 
weeks, and twelve weeks and six months, in conjunction with bone scanning, CT/MRI, where 
clinically appropriate, unless the patient is on a clinical trial that dictates otherwise. These will 
be compared with baseline scans and available prior scans . 
 
2.0 
OBJECTIVES: 
The primary objectives of this study are: 
 
2.1    Homogeneity of the metabolism of prostate cancer metastases: To explore the FDG 
and CMET metabolism in tumors by PET in progressive prostate cancer, on a site by site 
basis. 

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2.1 Diagnostic ability: To explore the diagnostic ability of FDG and, in selected cases 11C- 
methionine, by comparing PET scanning to standard of care diagnostic studies, which 
include the 99m-Tc bone scan, computed tomography, and magnetic resonance imaging. 
 
2.2. Treatment effects: To explore changes in the relative tumor uptake, as defined by such 
quantitative measures as the standardized uptake value (SUV) and the total lesion 
metabolism (TLM), for FDG and 11C-methionine after systemic therapy(ies). To 
determine which tracer, FDG or CMET, surrogates for glucose metabolism and amino 
acid synthesis respectively, is the superior predictor of treatment response. 
2.3 
FDHT Imaging: In selected patients who are progressing and have advanced androgen- 
independent prostate cancer, we will develop pilot data on the in vivo targeting and 
biokinetics of F-18 FDHT by PET imaging. When feasible, biopsy samples will be 
obtained from index lesions in order to correlate the level of FDHT uptake with androgen 
receptor expression, as determined by immunohistochemistry. 
 
3.0 
RATIONALE AND BACKGROUND 
3.1 
Disease Information 
 
The patterns of spread of prostate cancers make it difficult to quantify tumor regression 
and progression in a reproducible way, because the standard phase II response criteria do 
not apply.(3) Bone, the most common site of spread, is particularly difficult because 
tumor growth in the marrow results in osteoblastic changes on plain radiographs which, 
in the end stage, results in complete replacement of the marrow space. While most 
physicians accept that sclerotic healing of a lytic lesion constitutes tumor regression, the 
sequential monitoring of lesions that are initially sclerotic is problematic as histologic 
reversion to a normal bone architecture rarely occurs. Even if all tumor cells are 
destroyed there may be no visible plain radiographic changes. In these cases, only a direct 
biopsy can determine if viable tumor cells are present. 
 
To circumvent this problem, and before the availability of PSA measurements, many 
investigators restricted entry on clinical trials to selected patients with bi-dimensionally 
measurable tumor masses.(4) This excluded the majority of patients from trials. Others 
attempted to assess response by combining subjective parameters, such as changes in 
performance status or pain relief, with indirect objective measures such as changes in 
hemoglobin or weight.(5) Over the past five years, we have developed a clinical trial 
methodology to evaluate new therapeutic approaches based on serial PSA 
determinations.(6) Entry requires clear documentation of disease progression, controlling 
for the hormone sensitivity of the tumor,(7) controlling for steroid hormone withdrawal 
responses,(8) and reporting the outcomes of the trial on the basis of post-therapy changes 
in PSA, measurable disease, and radionuclide imaging independently.(6) The definition 
of progression includes serial elevations in PSA values, which have been shown to 
antedate clinical and radiographic evidence of progression for patients with both 
hormone-naive and hormonally relapsing disease. 

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More recently, we developed a clinical states model for progression that highlights easily 
recognized clinical milestones, and provides a background to determine when to 
recommend treatment, to select a particular approach, and to assess treatment effects.(9) 
In this trial, patients with progressive disease in all disease states will be studied. 
 
 
 
 
 
 
 
 
 
 
 
3.2 
Conventional Imaging Modalities 
 
Radionuclide bone scanning: Standard bone scintigraphy is limited because it reflects the 
reaction of bone to surrounding cancer rather than providing a direct measure of cancer 
activity. In one series of patients with a total of 100 bone scan abnormalities, 57 were 
confirmed by plain radiographs, and 42 showed normal corresponding plain radiographs; 
and 1 patient had a radiographic abnormality not detected by scintigraphy.(10) The flare 
phenomenon, a paradoxical increase in intensity after successful therapy, further 
complicates the interpretation of scans on a serial basis.(11) To begin to address these 
questions, we have developed a novel bone scan index,(12) which quantifies the 
percentage of bone involved by tumor, but this too does not provide an index of the 
viability of tumor. 
 
Cross sectional imaging: Cross-sectional imaging modalities used in the evaluation of 
prostate cancer include computed tomography (CT) and magnetic resonance imaging 
(MRI). The utility of each of these modalities varies according to stage of the disease. CT 
is well suited for the detection of soft tissue disease, but has limited utility in assessing 
early changes in bone. It is not sensitive in detecting microscopic nodal disease or for 
detecting tumor in non-enlarged lymph nodes. In our experience, CT is also limited in 
evaluating disease confined to the prostate and adjacent area. MRI imaging is considered 
the modality of choice for the most accurate assessment in the region of the prostate, 
neurovascular bundles and seminal vesicles.(13) MRI can also detect soft tissue disease 
and is most useful to corroborate bone scintigraphic findings, since the earliest 
involvement is thought to be present in the bone marrow. MRI exhibits the highest 
sensitivity in the axial skeleton and pelvis, and is less effective in the ribs, chest wall, and 
skull. 
 
3.3 
Positron Emission Tomography 
 
Positron Emission Tomography (PET) has the potential to detect the altered metabolism 
of the malignant state. This may improve detection as well as permit the quantitative 
monitoring of metabolic changes in tumors that are under treatment. Of the many 
radiopharmaceuticals used for PET scanning, the glucose analogs have been highly 
successful for imaging of a variety of human tumors and for monitoring response to 
therapy.(14) However, in a trial using FDG and PET imaging in androgen independent 
prostate cancers at MSKCC, only 18% of the metastatic sites detected by conventional 
bone scintigraphy metabolized FDG sufficiently to be visualized on PET imaging(14). 
Our preliminary results for this study show that over 70% of the abnormalities visualized 
on  radionuclide  bone  scan  are  visible  using  FDG.  This  shows  the  importance  of 
Clinical 
Metastases: 
Castrate 
Clinical 
Metastases: 
Noncastrate 
Rising PSA 
Clinically 
Localized 
Disease 
Initial Prostate 
Evaluation: 
No Cancer 
Diagnosis 

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Amended: 4/10/07 
Page 6 of 16 
 
 
controlling for disease progression prior to imaging as is required in this trial.(1) 
Recently, Dr. David Agus and coworkers studied the uptake of FDG in the androgen- 
dependent human prostate cancer xenograft CWR-22. High uptake values were recorded, 
but of greater interest was the finding that FDG uptake decreased within 24 hours 
following castration. The decrease preceded declines in PSA, suggesting that PET 
imaging may be useful to monitor the response to treatment.(15) This suggests that for 
many patients, serial changes in FDG may be useful to monitor disease status. One 
limitation of the study, however, was that entry did not require a strict definition of 
disease progression prior to imaging. 
 
One hypothesis under study in this trial is whether 11C- methionine is more effective in 
visualizing androgen independent prostate cancer by PET imaging. The essential amino 
acid, 11C- methionine is a tracer that has been used to image a variety of human 
tumors.(16-18) In a preliminary report from Nilsson and coworkers, 12 patients with 
androgen independent prostate cancer underwent PET imaging with 11C- methionine. 
Uptake of the radiotracer was discovered in all known sites of bone and soft tissue lesions 
of patients visualized by standard bone scintigraphy or cross sectional imaging.(19) Ten 
patients had repeat PET scans. Those who responded to treatment had a reduced uptake 
of the radiotracer with no changes in the images generated by standard techniques. Our 
ongoing results show that 93% of index lesions were visible using 11C-methionine and 
83% visible using FDG.(1) These biodistribution and metabolic findings require 
additional verification in a larger series. 
 
11C-methionine and 18FDG whole body imaging 
 
We have performed a preliminary comparative study of 11C-methionine and 18F-FDG in 
10 patients with prostate cancer, who were referred for PET imaging with progressive 
prostate cancer, as defined by serially rising PSA values and one or more new (“index”) 
lesions on bone scan. Among the 10 patients, there were 13 such index lesions on bone 
scans. 11C-methionine imaged 12/13 (93%), and 18F-FDG 11/13 (83%) index lesions. 
The one lesion not imaged by CMET was subsequently judged to be avascular necrosis, 
based on its pattern of resolution on subsequent bone scans. 11C-methionine is very 
rapidly cleared from the blood, with rapid equilibration (10 minutes) in the tumor. The 
tumor uptake of 11C-methionine is consistently high, with standard uptake values (SUVs) 
ranging from 4.9 to 11.6. We have therefore shown that high-quality whole body PET 
imaging is feasible with 11C-methionine, despite the short 20-min physical half-life of 
carbon-11. 
As accrual to the study has been limited by the need to generate 11C-methionine 
immediately prior to administration, and based on our preliminary results showing that a 
higher percentage of tumors are visualized with FDG than previously anticipated, we 
plan to perform FDG scans in all patients, and 11C-methionine when it is available. In 
cases where uptake is visible with FDG, repeat studies will be conducted after therapeutic 
intervention. 
 
A few fully informed and consenting patients will be selected for studies with tracer 
FDHT. We will choose subjects that have actively metabolizing tumors on FDG or 
CMET, and who are expected to have high expression of androgen receptor such as 
hormonally naïve patients. In the first 10 subjects, we will perform dynamic acquisitions 
to study the rate of uptake over index lesions for 1 hour. If possible, we will obtain a 
biopsy of this site for immunohistochemical staining of AR expression. 

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3.4 
Correlations between PET and standard imaging modalities: 
 
In a preliminary analysis of 157 lesions in 18 patients with progressive metastatic disease, 
we have shown a high (71%) degree of concordance between FDG avid lesions and 
osseous metastases visualized by bone scans. In selected cases, lesions appeared on FDG 
PET earlier in the disease course relative to the bone scans. The correlation between 
FDG avid lesions and radiographically evident soft tissue disease is limited in areas 
around the ureters and bladder, through which the tracer is excreted ((20) and Morris et 
al, unpublished). As well, preliminary data suggest that changes in SUV may be useful 
as an early outcome measure in patients with castrate metastatic disease undergoing 
chemotherapy.(21) These data require confirmation and validation using larger numbers 
of patients and lesions. In addition, such associations cannot be presumed to be 
applicable to other disease states. To date, we have focused on patients with progressive 
metastatic disease; this protocol will include patients from all disease states. 
 
Additional studies are therefore required to: (1) assess FDG-PET in prostate cancer 
patients with progressive disease of all clinical states, (2) to confirm these findings where 
the metastatic sites are rigorously assessed with larger numbers of patients, (3) to 
compare PET findings with those of standard bone scintigraphy, CT, or MRI, and (4) to 
compare posttreatment changes in SUV with changes in standard outcome measures such 
as PSA. 
 
3.4 
Equipment Information (PET) 
 
The ADVANCE (General Electric Medical Systems) whole body PET scanner consists 
of 336 BGO detector units arranged to form 18 rings (separated by 1 mm retractable 
tungsten septa) with 672 crystals each, giving 35 contiguous 2-D image planes through an 
axial field of view of 15.2 cm. The maximum transaxial FOV is 55 cm in diameter 
through a 58 cm diameter patient port. The average axial resolution (FWHM) is 4.2 mm 
at r=0 cm; 5.5 mm at r = 10 cm; and 6.6 mm at r = 20 cm. Total system sensitivity is 223 
Kcps/uCi/cc with septa in and 1200 Kcps/uCi/cc with septa out. Reconstruction time is 
<2 seconds per 4.25 mm slice at 128x128 pixels.(22,23) 
 
3.5 
Standard Evaluation Schema 
 
The initial evaluation of a patient with progressive disease be it locoregional or 
metastatic, androgen dependent or independent, is directed toward determining disease 
extent and pattern of spread. This usually consists of a history and physical examination, 
a hematology, chemical and PSA profile, and for patients with androgen independent 
disease, a serum testosterone level.  Imaging studies typically include a chest radiograph, 
a CT of the abdomen and pelvis, and radionuclide bone scan. To assess the prostate and 
pelvic lymph nodes, magnetic resonance imaging is recommended, because CT scanning 
is too insensitive to accurately reflect the presence or absence of disease, and to 
determine local extent within the prostate itself. Our experience to date shows that 
frequently, magnetic resonance imaging of the pelvis is negative, and because some 
patients do not have pelvic disease, we will only advise this test when clinically 
indicated. Further, because the results of CT and/or MR imaging do not change in the two 
week interval following an intervention, we will no longer require that all studies be 
completed prior to the performance of the PET scan. The presence or absence of other 
medical co-morbidities, such as cardiac or pulmonary disease, frequently mandates 
additional testing in this patient population. 

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Page 8 of 16 
 
 
4.0 
BACKGROUND DRUG INFORMATION 
4.1 
11C- methionine: L-methyl-11C- methionine has undergone general safety testing. The 
preparation is apyrogenic and sterile, and is prepared in a form suitable for injection. It is 
formulated by the radiochemistry/cyclotron facility using established procedures. The 
individual patient doses will be tested by appropriate quality control procedures to ensure 
expected potency, purity, and apyrogenicity. An IND is not required at this time, as this 
study will be submitted for authorization and approval under the MSKCC Committee on 
radiation (Title 21, Part 361.1 of the Federal Code of Regulations). The product is 
produced at high specific activity, has been used on multiple occasions in humans at 
other centers, and has no evidence of pharmacological effect. 
 
4.2 
[18F]-fluoro-2-deoxy-D-glucose: FDG has undergone general safety testing, is approved 
by the FDA, and is on the hospital formulary for use as a diagnostic agent. 
 
4.3 
[18F]-dihydrotestosterone (FDHT): Dihydrotestosterone is the predominant testosterone  
that is present in the prostate gland itself in animals. Welch, Katzenellenbogen and their 
colleagues have developed a variety of tracers for study of the androgen receptor. 
Preclinical evaluation of a variety of fluorinated steroids was undertaken in baboons. 
16-[18F]-fluoro-5dihydrotestosterone (FDHT) appeared to be the preferred agent in 
mammals due to favorable biodistribution and demonstrable androgen receptor binding. 
The plasma protein sex-hormone binding globulin (SHBG) is found in high concentration 
in primates in contradistinction to rodents. Plasma SHBG may therefore explain the 
higher uptake of FDHT into baboon prostatic tissue in comparison to other fluorinated 
steroids possibly related to reduced metabolic breakdown. The activity of FDHT in the 
region of the prostate peaked at 30-90 minutes post injection. At 60 minutes there was a 
high ratio of prostatic activity to soft tissue, blood and bone (>6:1, >3.5:1 and >7:1 
respectively).(24,25) It appears that the ligand FDHT exhibits sufficient specific binding 
to androgen receptors in vivo to allow imaging of androgen receptor-positive tissue. 
Accordingly, in the orchiectomized host, where androgen receptor occupancy would be 
expected to be low, it seems feasible to image androgen receptor-positive human cancers. 
A protocol for the usage of this tracer in humans has yet to be developed. Using dynamic 
imaging with venous blood sampling we will determine the feasibility of use of this tracer 
in humans. 
Washington University has initiated a clinical trial, and has studied 6 patients with PET 
imaging. The study is done under the auspices of the Washington University Radioactive 
Drug Research Committee (B. Siegal, Chairman), and this has been the basis for the 
dosimetry reported in the Appendices. No toxicity has been observed. 
 
5.0 
PATIENT ELIGIBILITY 
5.1 
Entry requirements: 
 
5.1.1 
Patients with histologically confirmed prostate adenocarcinoma. 
 
5.1.2 
Disease progression as demonstrated by: 
 
5.1.2.1 
A  50% increase in PSA which is sustained for a minimum of 3 
observations obtained at least 1 week apart; 

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OR 
 
5.1.2.2 
Development of new lesions or an increase in pre-existing lesions on 
bone scintigraphy, or in measurable disease by CT or MRI. 
 
5.1.3 
Karnofsky performance status > 60%. 
 
5.1.4 
Informed consent. 
 
5.2 
Exclusion Criteria: 
 
5.2.1 
Patients with an active infection not controlled by antibiotics. 
 
5.2.2 
Patients with clinically significant pulmonary or cardiac (NYHA Class III or IV) 
disease. 
 
6.0 
PRETREATMENT EVALUATION 
6.1 
History and physical examination 
 
6.2 
Laboratory studies: CBC, PSA (within 2 weeks of study entry); serum testosterone 
(within 4 weeks of study entry). 
 
6.3 
Urinalysis (if normal, no culture required) to exclude urinary tract infection (within 2 
weeks). 
 
6.4 
Bone scintigraphy (within 6 weeks of study entry or up to 2 weeks after entry); using the 
MSKCC bone scan index (appendix D) 
 
6.5 
Computed tomography of abdomen and pelvis (within 6 weeks before entry or up to 2 
weeks after entry) and/or Modified MRI of the pelvis to image the prostate (includes 
retroperitoneum) at MSKCC within 6 weeks before entry or up to 2 weeks after entry as 
clinically indicated.) 
 
6.6 
Chest radiograph (within 6 weeks before entry or up to 2 weeks after entry) 
 
7.0 
TREATMENT PLAN 
7.1 
Patients will be fasting for 6 hours prior to PET imaging, with the exception of liberal 
water intake which is encouraged. 
 
7.2 
A blood glucose level will be obtained prior to FDG administration. Elevated baseline 
serum glucose levels have been reported to cause false negative results with FDG-PET 
imaging. 
 
7.3 
An intravenous catheter (heplock) will be placed in the nuclear medicine department for 
radiopharmaceutical administration and blood sampling. 
 
7.4 
11C-methionine: Each patient will receive 10 -15 mCi of 11C-methionine intravenously 
with PET imaging beginning 10 minutes after the injection, for approximately 60 minutes 
total using standard imaging procedures, as described (B). 

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FDG: Each patient will receive 10 mCi of FDG intravenously followed by PET imaging 
for a total imaging time of approximately 60 to 75 minutes using standard imaging 
procedures. 
 
7.5 
Patients will be imaged using the ADVANCE (General Electric Medical Systems) whole 
body PET scanner. 
 
7.6 
The radiopharmacy will keep a log of all doses administered. 
 
7.7 
The intravenous catheter will be removed at the conclusion of imaging. 
 
7.8 
Unless otherwise specified by a clinical trial, patients can undergo serial scans 4 weeks, 
12 weeks, and 6 months following the baseline scan. If the patient is receiving treatment 
on a clinical trial, then PET scanning will be performed according to the schedule 
outlined in the treatment trial. No more than 7 repeat studies will be performed in a one- 
year period. This ensures that the total exposure is less than 15 rads to the organ receiving 
the highest radiation dose per year (the left ventricle) (See appendix ). 
 
7.9 
Baseline 18F-FDHT scans can be performed within two weeks of a baseline FDG scan, as 
long as there has been no change to the patient’s treatment in the interim. Those patients 
selected for serial PET imaging with 18F-FDHT will have all additional 18F-FDHT scans 
performed the day after the FDG scan. An index lesion will be selected from the previous 
CMET or FDG scan. The patient will be positioned on the scanner, with the index lesion 
positioned at the center of the 14.25 cm field of view. A 5 minute transmission scan will 
be performed to verify the correct location of the patient on the scanner. A dynamic PET 
image acquisition will be initiated immediately post injection with 10 mCi (370 MBq) of 
18F-FDHT, to evaluate the rate of 18F-FDHT uptake in the index lesion. Dynamic scans 
consisting of 10 one-minute, and 10 five-minute frames will be acquired (total duration = 
60 minutes). Up to a maximum of 17 serial blood samples will be taken at the following 
collection times when possible: 0, 0.5, 1, 1.5, 2, 3, 4, 5, 7, 10, 15, 20, 30, 40, 50, 60, and 
120 minutes post injection. Blood samples will be counted on a well scintillation counter 
(LKB Wallac), to determine the blood clearance kinetics of the radiotracer. After the 
dynamic scan, a whole body scan will be performed, either in immediate continuation or 
following a short rest, if required by the patient. The whole body scan will follow our 
department 18F-FDG guidelines of 6-minute emission and 4-minute transmission scans 
per field-of-view. In selected patients, additional views, partial or total body, will be 
acquired between 2-4 hours post injection when possible, to assess retention of the tracer 
in the tumor. All images will be reconstructed by filtered backprojection and iterative 
reconstruction, with attenuation correction. The kinetics of tumor uptake will be 
determined by region-of-interest (ROI) analysis of the dynamic image data set. This data 
will provide plots of the tumor relative specific activity (Ci/cc of the 18F-FDHT) versus 
time post administration. Region-of-interest analysis over tissues e.g. brain, heart, liver, 
spleen, kidney, bladder, muscle and tumor on the decay corrected whole body images 
will enable relative uptake ratios (tumor/normal tissues) of the 18F-FDHT to be 
determined at between 1-2 hours post 18F-FDHT injection. Changes in the absolute tumor 
uptake of 18F-FDHT per unit administered dose relative to normal organs should reflect 
changes in androgen level expression in the tumor. 
 
7.9.1 
Patients will have a testosterone, sex hormone binding globulin, and DHT level 
drawn within 2 weeks prior to any FDHT scan. 

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8.0 
TOXICITY ASSESSMENT AND MANAGEMENT 
8.1 
No toxicity is anticipated with the described radiopharmaceutical preparations or PET 
scanning. The formulations and doses of radiotracers are below defined levels for 
radiation toxicity. (Title 21,361.1). 
 
8.2 
Dosimetry Assessment: The total rad dose is below the limits set by the FDA for 
investigational radioactive drug studies, and falls within the Radioactive Drug Research 
Committee guidelines as defined by 5 rad/single organ/dose and 5 rad/year to the whole 
body, hematopoietic organs, gonads and eyes. 
 
9.1 
SERIOUS ADVERSE EVENTS (SAE) REPORTING 
Any SAE must be reported to the IRB as soon as possible but no later than 5 calendar days. The 
IRB requires a Clinical Research Database (CRDB) AE report to be delivered to the Institutional 
SAE Manager (307 East 63rd Street, 1st Floor) containing the following information: 
Fields populated from the CRDB: 
• 
Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
• 
Medical record number 
• 
Disease/histology (if applicable) 
• 
Protocol number and title 
 
Data needing to be entered: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
Relationship of the adverse event to the treatment (drug, device, or intervention) 
• 
If the AE was expected 
• 
The severity of the AE 
• 
The intervention 
• 
Detailed text that includes the following information: 
o A explanation of how the AE was handled 
o A description of the subject's condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form 
The PI’s signature and the date it was signed are required on the completed report. 
For IND/IDE protocols: 
The CRDB AE report should be completed as above and the FDA assigned IND/IDE number 
written at the top of the report. The report will be forwarded to the FDA by the Institutional SAE 
Manager through the IND Office. 
 
10.0 
CRITERIA FOR REMOVAL FROM STUDY 
Patients will be removed from the study at their request or for failure to comply with protocol 
requirements. 

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11.0 
DATA ANALYSIS 
The study design is such that the PET scan will be compared to the gold standards for the 
determination of sites of tumor. Each imaging modality will be independently evaluated. The 
PET protocol data analysis form (appendix E) allows the selection and recording of involved 
sites. Following independent recording and submission of the imaging interpretation data to the 
protocol data manager (JM), sites of uptake on PET scan will be compared to the detected sites by 
other imaging modalities with concurrence by HS and SML. 
 
CT: Lesions on computed tomography will be selected and recorded which are reproducibly 
bidimensionally measurable (greatest dimension X perpendicular to greatest dimension) including 
adenopathy in the pelvis or retroperitoneum and soft tissue masses. 
 
MRI: T1 and T2 weighted sequences will be obtained for each modified MRI scan of the pelvis 
which includes the retroperitoneum. Reproducible bidimensionally measurable (greatest 
dimension X perpendicular to greatest dimension) lesions will be selected and recorded including 
adenopathy in the pelvis or retroperitoneum, soft tissue masses, and bone metastasis. 
 
PET: PET images will be interpreted and the results recorded on a standardized form (appendix 
E). The transmission data will be displayed alongside the emission corrected scans to allow 
anatomic localization of activity. The images should be reviewed in all standard planes and a 
volumetric projection if available. 
 
Visual analysis will require the identification of abnormal uptake as being greater than 
background activity on the attenuation corrected images. Features of the primary tumor, including 
the presence or absence of metastases, will be recorded on a 5 point scale. (5 = definitely 
abnormal, 4 = probably abnormal, 3 = indeterminate, 2 = probably normal, 1 = definitely normal). 
Estimates of size will be provided for each lesion. 
 
Using the attenuation corrected images, semiquantitative analysis will require identifying regions 
of interest (ROI) in areas of abnormality and the standard uptake value will be calculated based 
on the following formula: 
 
 
SUV 
= 
decay corrected mean ROI activity (mCi/ml) 
 
 
injected dose (mCi)/body wt (g) 
Lesions will be indicative of malignancy if the SUV is > 2.5 in soft tissue or > 2.0 in bone. 
Values below these levels will be considered benign. Lesion to background ratios will also be 
calculated for the transmission corrected scans. 
 
This analysis will be used on all selected PET scans, including retrospectively analyzing PET 
scans received prior to patient registration. 
 
12.0 
BIOSTATISTICAL    CONSIDERATIONS 
To assess the diagnostic implications of PET scanning with 11C-methionine and FDG, the 
sensitivity and specificity will be estimated by comparing PET scan results to "standard 
of care" diagnostic measures that include the 99m-Tc bone scan, computed tomography, 
and magnetic resonance imaging. Each patient will receive these standard diagnostic 
measures  and  PET  scanning  with  both  11C-methionine  and  FDG.  The  diagnostic 

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"standard of care" scan (bone scan, CT or MRI) will be recorded as positive or negative 
for each site: bone and bone marrow and/or soft tissue 
 
The sensitivity of PET imaging with 11C-methionine or FDG is defined as the ability of 
PET scanning to identify those metastatic lesions diagnosed by standard diagnosis using 
bone scan, CT, or MRI as "gold standard" and is determined by the proportion of patients 
with positive lesions as diagnosed by standard method who were identified by the PET 
imaging. The sensitivity will be measured for both androgen-dependent and androgen- 
independent prostate cancer patients, and on a site by site basis (bone and bone marrow, 
and soft tissue). 
Assuming at least one site in each patient is assessed positive by the gold standard, the 
sensitivity of FDG and 11C-methionine can be conservatively estimated to within +/- 
0.16. The total sample size for this study is 265. 
 
To explore changes in metabolism during treatment based on PET imaging, the average 
SUV value will be recorded at 4 weeks, 12 weeks, and 6 months following the baseline 
scan. Summary measures such as the slope of the SUV trajectory and the area under the 
SUV curve will be recorded separately for FDG and 11C-methionine. 
 
13.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION 
PROCEDURES 
 
13.2 
Research Participant Registration (PPR) 
 
The following person(s) can obtain informed consent: 
 
Michael Morris, MD 
Howard Scher, MD 
Susan Slovin, MD, PhD 
 
Confirm in the electronic medical record that the patient has received the Notice of 
Privacy Practice.  This must be obtained before the eligibility confirmation and obtaining 
of the research informed consent. 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject 
Eligibility. 
 
Obtain written informed consent, by following procedures defined in section entitled 
Informed Consent Procedures. 
 
All particpants must be registered through the Protocol Participant Registration (PPR) 
Office at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through 
Friday from 8:30am - 5:30pm at (646) 735-8000. The PPR fax numbers are (646) 735- 
0008 and  (646) 735-0003.  Registrations can be phoned in or faxed. The completed 
signature page of the informed consent form, the completed signature page of the 
Research Authorization and a completed Eligibility Checklist must be faxed to PPR. 

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During the registration process registering individuals will be required to answer specific 
eligibility questions and provide the following information: 
Registering Individual 
[Last, First Name] 
Notice of Privacy Status 
[Yes, No, N/A] 
Research Authorization 
[Date] 
MSKCC IRB Protocol# 
Attending of Record (if applicable)  
[Last, First Name] 
Consenting Professional 
[Last, First Name] 
Informed Consent Date 
Participant's Full Name 
[Last, First Name] 
Participant MRN 
 
14.1 
PROTECTION OF HUMAN SUBJECTS 
 
14.2 
Privacy 
 
It is the responsibility of the Research Staff to ensure that Memorial Sloan-Kettering Cancer 
Center has on file a written acknowledgment of receipt by the subject of the Center’s Notice of 
Privacy Practices. If the subject has not already done so, he/she must sign such an 
acknowledgment before participating in this study. 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals described in the Research 
Authorization form. A Research Authorization form must be completed by the Principal 
Investigator and approved by the IRB and Privacy Board. 
 
 
15.1 
INFORMED CONSENT PROCEDURES 
Patients will be required to sign a statement of informed consent (appendix F), which meets the 
requirements of the code of Federal Regulations (Federal Register Vol. 46, No. 17, Jan. 27, 1981, 
part 50) and the IRB of this center. 
 
 
Documentation of informed consent: The informed consent will be signed by the patient and 
consenting physician in triplicate. A signed original consent form is given to the patient. The 
second original is placed in the patient's medical record and the third original is kept on file in the 
office of clinical research. 
 
15.2 
Research Authorization 
 
Procedures for obtaining Research Authorization: Before any protocol-specific procedures are 
carried out, investigators and/or designated staff will fully explain the details of the protocol, 
study procedures, and the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must sign the Research Authorization 
component of the informed consent form.   The Research Authorization requires a separate 

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signature from the patient.   The original signed documents will become part of the patient’s 
medical record, and each patient will receive a copy of the signed documents. 
 
 
 
 
 
 
16. 
BIBLIOGRAPHY 
 
(1) 
Macapinlac HA, Humm JL, Akhurst T, et al: Differential metabolism and pharmacokinetics of L- 
[1-11C]-methionine and 2-[18F] fluro-2-deoxy-D-glucose (FDG) in androgen independent 
prostate cancer. Clin Pos Imag 2:173-181, 1999 
 
(2) 
Liu A, Dence CS, Welch MJ, et al: Fluorine labeled androgens: radiochemical synthesis and 
tissue distribution studies on six fluorine-substituted androgens, potential imaging agents for 
prostate cancer. J Nucl Med 33:724-734, 1992 
 
(3) 
Yagoda A, Watson RC, Natale RB, et al: A critical analysis of response criteria in patients with 
prostatic cancer treated with cis-diamminedichloride platinum II. Cancer 44:1553-1562, 1979 
 
(4) 
Scher HI, Yagoda A: Clinical trials in prostatic cancer: Methodology and controversies. In 
Adenocarcinoma of the Prostate (Bruce AW, Trachtenberg J, eds). New York: Springer-Verlag, 
1987, pp 197-220 
 
(5) 
Robinson MRG: Carcinoma of the prostate: objective criteria of response. Am.J.Clin.Oncol. 
Suppl.2:s48-s52, 1988 
 
(6) 
Scher HI, Mazumdar M, Kelly WK: Clinical trials in relapsed prostate cancer: defining the 
target. J Natl Cancer Inst 88:1623-1634, 1996 
 
(7) 
Scher HI, Steineck G, Kelly WK: Hormone-refractory ("D3") prostate cancer: refining the 
concept. Urology 46:142-148, 1995 
 
(8) 
Scher HI, Kelly WK: The flutamide withdrawal syndrome: its impact on clinical trials in 
hormone-refractory prostatic cancer. J Clin.Oncol. 11:1566-1572, 1993 
 
(9) 
Scher HI, Heller G: Clinical states in prostate cancer: towards a dynamic model of disease 
progression. Urology 55:323-327, 2000 
 
(10) 
Jones SC, Alavi A, Christman D, et al: The radiation dosimetry of 2-[F-18] fluoro-D-glucose in 
man. J Nuc Med 23:613-617, 1982 
 
(11) 
Larson SM, Schwartz LH: Advances in imaging. Semin.Oncol. 21:598-606, 1994 
 
(12) 
Sabbatini P, Yeung H, Imbriaco M, et al: The correlation of serial bone scintigraphy and PSA 
determinations 
in 
patients 
(Pts) 
with 
androgen 
independent 
prostate 
cancer. 
Proc.Am.Soc.Clin.Oncol. 15:254, 1996 

IRB#: 97-007A(12) 
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Page 16 of 16 
 
 
(13) 
Rifkin M: Comparison of magnetic resonance imaging and ultrasonography in staging early 
prostate cancer. Results of a multi-institutional cooperative trial. Invest.Radiol. 26:1024-1025, 
1991 
 
(14) 
Larson SM: Positron Emission Tomography in Oncology and Allied Diseases. In Cancer: 
Principles and Practice of Oncology. (DeVita VT, Hellman S, Rosenberg SA, eds). Philadelphia: 
J.B. Lippincott, 1989, pp 1-12 
 
(15) 
Agus D, Golde DW, Sgouros G, et al: Change in deoxyglucose accumulation is a biologic 
surrogate for response to hormone manipulation in a human xenograft model for prostate cancer. 
Proc Amer Assoc Cancer Res 39:(Abstract 1613), 1998 
 
(16) 
Lindholm P, Leskinen-Kallio S, Grenman R, et al: Evaluation of response to radiotherapy in head 
and 
neck 
cancer 
by 
positron 
emission 
tomography 
and 
[11C]-methionine. 
Int.J 
Radiat.Oncol.Biol.Phys. 32:787-794, 1956 
 
(17) 
Kubota K, Matsuzawa T, Ito M, et al: Lung tumor imaging by positron emission tomography 
using C-11 L-methionine. J Nucl.Med. 26:37-42, 1985 
 
(18) 
Mosskin M, Bergstrom M, Collins VP, et al: Postiron emission tomography with 11C-methionine 
of intracranial tumors compared with histology of multiple biopsies. Acta Radiol.[Oncol]. 
369:157-160, 1986 
 
(19) 
Nilsson S, Kalkner K-M, Ginman C, et al: C-11 methionine positron emission tomography in the 
management of prostatic carcinoma. Antibody, Immunoconjugates and Radiopharmaceuticals 
8:23, 1995 
 
(20) 
Osman I, Akhurst T, Macapinlac H, et al: C-11 methionine and F-18 PET imaging: use in the 
evaluation of progressive prostate cancer. Proc Am Soc Clin Oncol 18:abstract 1203, 1998 
 
(21) 
Morris MJ, Akhurst T, Kelly K, et al: PET as an outcome measure for metastatic prostate cancer 
(PC) treated with chemotherapy. Proc Amer Assoc Clin Oncol , 2000 (submitted) 
 
(22) 
Degrado TR, Turkington TG, Williams JJ: Performance characteristics of a new generation PET 
scanner. J Nucl.Med. 34(5):101P, 1993 
 
(23) 
Dahlbom M, Hoffman EJ, Hoh CK: Whole body Positron Emission Tomography: Part I. Methods 
and Performance Characteristics. J Nucl.Med. 33:1191-1199, 1992 
 
(24) 
Choe YS, Lidstrom PJ, Chi DY, et al: Synthesis of 11-[18F]Fluoro-5−dihydrotestosterone and 
11-[18F]Fluoro-19-nor-5-dihydrotestosterone: Preparation 
via 
halofluorination-reduction, 
receptor binding, and tissue distribution. J. Med. Chem. 38:816-825, 1995 
 
(25) 
Bonasera TA, O'Neil JP, Xu M, et al: Preclinical evaluation of Fluorine-18-labeled androgen 
receptor ligands in baboons. J Nucl Med 37:1009-1015, 1996