Summary of Studies on Carcinoid Tumors Presented at the Society of Nuclear Medicine

51st Annual Society of Nuclear Medicine Meeting
June 19-23, 2004, Philadelphia

Prepared by: Seza A. Gulec, MD

COMPARISON BETWEEN I-123 MIBG AND IN-111 OCTREOTIDE IN THE
DETECTION OF NEUROENDOCRINE TUMORS.
W. Gayed et al. University of Texas M.D. Anderson Cancer Center, Houston, TX
Twenty patients were included in the study (4 carcinoid, 2 medullary thyroid cancer, 2
pheochromocytoma, 2 islet cell tumors, 1 paraganglioma, 4 non-neuroendocine tumors, 5
no cancer). Six patients had positive MIBG scan and 5 had positive Octreoscans. The
sensitivity, specificity, positive and negative predictive values for the MIBG scans were
50, 100, 100, and 63% and for Octreoscan were 45, 100, 100, and 62%. There was no
statistically significant difference in the performance of the two procedures with p=1.0.
MIBG scan was positive in one patient with pheochromocytoma, one patient with
medullary thyroid cancer and one patient with carcinoid while Octreoscans were
negative. Octreoscan was positive in one patient with carcinoid and another with islet cell
tumor when MIBG scans were negative.
The performance of I-123 MIBG and In-111 Octreotide in the detection of
neuroendocrine tumors was comparable with very high specificity and positive predictive
values.


HIGH DOSE I131 METAIODOBENZYLGUANIDINE (MIBG) THERAPY FOR
METASTATIC NEUROENDOCRINE TUMORS.
M. Stachowiak et al. University of Texas M.D. Anderson Cancer Center, Houston, TX
Response to therapy was monitored using urine and blood chemical markers, quality of
life questionnaires, tumor size measurements by CT and tumor activity on subsequent
Iodine-123- MIBG scans. Of the fourteen patients, four have stable disease at this time
and the average time to progressive disease was 6.1 months. Three subjects died during
the study follow-up period due to disease progression.
The result of this protocol suggests that Iodine-131- MIBG is an alternative or additional
option for patients with neuroendocrine tumors that show uptake of Iodine-123 -MIBG
on diagnostic scans.


In-111 PENTETREOTIDE THERAPY IN REFRACTORY SST2+ WELLDIFFERENTIATED

NEUROENDOCRINE NEOPLASMS IN A COMMUNITY
HOSPITAL.
Le, L. Linares et al. LSUHSC New Orleans, LA
85 patients (46 females) were treated with an average dose of 487.9 mCi of In-111
pentetreotide. The median age was 54.9 yrs. The majority (90%) of patients had a welldifferentiated
neuroendocrine tumor (such as carcinoid or pancreatic islet cell carcinoma)
and Grade 1 to 4 uptake on the diagnostic In-111 pentetreotide scan. 142 treatments were
delivered with 41 patients receiving 2 or more treatments (28 patients were treated twice;
10 patients received 3 doses and 3 patients received 4 doses). The baseline creatinine
clearance was 93 ml/min. For the 41 patients receiving one more treatments, subsequent
creatinine clearances were 82.8, 95.2 and 81.9 ml/min following a cumulative dose of
493, 986 and 1,483 mCi, respectively. Treatment-related myelosuppression or
myelodysplasia was not observed. The median survival was 22.1 months from the time of
the first In-111 pentetreotide treatment and 84.3 months from the time of diagnosis.
In-111 pentetreotide therapy can be safely administered in a community hospital setting
and results in a median survival of 22.1 months in patients with refractory sst2+
metastatic well-differentiated neuroendocrine malignancies.


MINIMUM 1 YEAR PROGRESSION AND OVERALL SURVIVAL DATA IN

PATIENTS TREATED WITH Y-90 LANREOTIDE.
J. R. Buscombe et al. Royal Free Hospital, London, United Kingdom
Using formal criteria of response only 3 patients (10%) had a partial response. A further
15 (50%) had disease stability, though many of these had a minor radiological response.
At 12 months 21 patients had radiological evidence of progression with a median
progression free survival of 7 months. However of those patients showing stability or
response, at 3 months, 7 had no further evidence of progression during the follow up
phase with a median progression free survival was 13 months. A total of 13 patients died
during the follow-up period so the median overall survival has not been reached however
7 deaths (58% mortality)occurred in the 12 patients with disease progression at 3 months
compared with only 6 (33% mortality) in those with stability or response. Haematological
toxicity occurred in 6 patients, 2 requiring supportive therapy. Both of these had
disseminated progressive disease
It would appear that 60% of patients receiving Y-90 lanreotide received some benefit
from the treatment with evidence of stability or response at 3 months suggesting both an
improved progression free and overall survival.


18F]6-FLUORO-L-m-TYROSINE IN THE ASSESSMENT OF PATIENTS WITH

CARCINOID TUMORS.
C. J. Marriott et al. Hamilton Health Sciences, Hamilton, ON, Canada
In 3 of 4 patients tumour was identified with [18F]-FmT imaging; the fourth patient was
not demonstrated to have disease by any assessment and remains well. Of the 3 patients
with demonstrable tumor, CT imaging did not distinguish between post-operative
scarring and tumor in 2 and was negative in the third. Octreotide imaging was negative in
2 of 3 patients. 131I-MIBG did not visualize tumor which was positive on [18F]-FmT
imaging. No bowel activity was noted on [18F]-FmT images as compared to octreotide
imaging where substantial gut activity was seen. Renal excretion of [18F]-FmT was
prominent.

[18F]-FmT imaging appears to be more sensitive than octreotide imaging in the detection
of metastatic disease from carcinoid tumors. Absence of bowel activity contributes to
improved imaging. Renal excretion of [18F]-FmT results in interference from activity in
the bladder and ureters that could be reduced with diuretic administration. Improved
specificity is noted over anatomical imaging with CT.


EFFICACY OF INDIUM-111-LABELED OCTREOTIDE SCINTIGRAPHY IN

DETECTING SOMATOSTATIN RECEPTOR-RICH MALIGNANCY.
G. El-Haddad et al., Hospital of the University of Pennsylvania, Philadelphia, PA.
Among the 232 octreoscans, 112 were true positive, 88 were true negative, 27 were false
negative and 5 were false positive scans. Therefore the sensitivity was 81% (112 of 139
scans), the specificity was 95% (88 of 93 scans), the accuracy was 86% (200/232), the
positive predictive value (PPV) was 96% (112 of 117), and the negative predictive value
(NPV) was 76% (88 of 115).  data demonstrates that Indium-111-labeled pentetreotide
(Octreotide) scintigraphy has a very high specificity and positive predictive value in
detecting somatostatin receptor-rich malignancy. Its routine use as an effective clinical
modality is well justified.


CLINICAL APPLICATION OF SMS RECEPTOR PET/CT USING Ga-68-

DOTATOC IN CARCINOIDS.
M. Hofmann et al. Medical School Hannover, Hannover, Germany, University of
Essen, Essen, Germany, Radiological Chemistry, Kantosspital Basel, Basel,
Switzerland, Rayal Surrey County Hospital, London / Surrey, United Kingdom
CT showed 35 lesions, all seen on the PET. PET demonstrated 45 additional lesions. All
extra-hepatic soft tissue lesions on PET smaller than 10 mm could not be identified with
CT, but were retrospectively seen only on fused PET/CT images. Most bone lesions (<15
mm diameter) without soft tissue invasion were not detected by CT. PET yielded correct
anatomical alignment in 65% of the lesions. Especially the localization of bone lesions or
lesions near organ boundaries was frequently mis-judged on PET alone.
PET using Ga-68-DOTATOC is superior to CT in the detection of SMS-receptor positive
lesions, but PET/CT fusion is required for correct anatomical alignment of all lesions.
The application of PET/CT is most desirable in all SMS-receptor positive tumors and
may soon become the gold standard for staging and therapy control in SMS receptor
positive tumors.


FIRST CLINICAL APPLICATION OF THE NEW SMS RECEPTOR PET

RADIO-LIGAND GA-68-DOTANOC - A LIGAND WITH BROAD SUBTYPE
SPECIFICITY -.
M. Hofmann et al. Medical School Hannover, Hannover, Germany; Radiological
Chemistry, Kantonsspital Basel, Basel, Switzerland.
Tumor uptake reached a plateau in most tumors at 60min p.i.. Ga-68-DOTANOC
delineated malignant lesions in: 6/6 carcinoid patients, 4/5 papillary thyroid cancers (no
accumulation in 1 papillary thyroid cancer metastasis after sequential radio-iodine
therapy with 17 GBq I-131-NaI), 1/4 medullary thyroid cancers (1 patient showed only a
slight uptake (SUVmean = 2.5)), 3/3 insulinomas were highly positive. Physiological
visceral SUVs were 7,5 (range 4-12) for liver, 20 (13-27) for spleen, 12 (range 8-17) for
the adrenal glands and 3,6 (range 3-8) for the pineal gland.
In this preliminary study , Ga-68-DOTANOC PET seemed to be feasible in the detection
of endocrine tumors such as carcinoids, papillary thyroid cancers and insulinomas
yielding high tumor to non-tumor ratios. However, it cannot be recommended in
medullary thyroid cancers.


In-111-DTPA-DGlu1-MINIGASTRIN IN COMPARISON TO In-111-DTPADPhe1-

Octreotide IN 87 PATIENTS WITH NEUROENDOCRINE TUMORS.
M. Gotthardt et al. Philipps-University of Marburg, Marburg,
87 patients were eligible for the study. 51 patients had carcinoid tumors, 3 gastrinomas, 2
glucagonomas, 1 insulinoma, 3 phaeochromocytomas/paragangliomas, 1 small cell lung
cancer (SCLC), and 26 medullary thyroid carcinomas (MTC). Somatostatin receptor
scintigraphy (SRS) revealed positive findings in 63.2% while Gastrin receptor
scintigraphy (GRS) was positive in 79.3%. SRS was superior to GRS in 27.6%, GRS was
superior to SRS in 40.2%. If patients with MTC are not considered, SRS is better than
GRS (82% versus 78.7%). In these patients, GRS performed better than SRS in 23%
while SRS was superior in 41%. In half of the SRS-negative patients, GRS was positive.
In patients with MTC, GRS performed clearly better reaching a sensitivity of 80.8%
versus 19.2% in SRS. In one patient with SCLC, GRS was strongly positive while SRS
was negative.
In patients with MTC, GRS is clearly superior to SRS. In patients with gastrointestinal
Neuroendocrine tumors (NET), SRS remains the standard other scintigraphic methods
have to be compared to. However, GRS is able to give additional diagnostic information
in 23% of these patients. Thus, GRS is a very promising new method for the scintigraphic
detection of NET. Especially in SRS negative patients, GRS should be performed.


NUCLEAR MEDICINE TECHNIQUES IN DIAGNOSIS AND TREATMENT OF CARCINOIDS

SUMMARY OF CARCINOID-RELATED PAPERS PRESENTED AT
THE SOCIETY OF NUCLEAR MEDICINE 50th ANNUAL MEETING

June 21-25, 2003, New Orleans, LA

Prepared by:
Seza Gulec, MD


DETECTION OF PRIMARY AND RECURRENT CARCINOID TUMORS WITH F-18 FDG PET:
COMPARISON WITH In-111 PENTETREOTIDE.

Y. Menda et al, University of Iowa College of Medicine, Iowa City,
FDG PET has a good sensitivity in carcinoid tumors and can be particularly helpful for detection of the
primary carcinoid tumor and metastatic spread in patients with a negative In-111 pentetreotide scan.
Further studies are needed to evaluate whether FDG positive/ In-111 pentetreotide negative carcinoid
tumors have a different clinical course compared with FDG negative In-ll1 pentetreotide positive
carcinoids.

IMAGING OF NEUROENDOCRINE TUMORS WITH 18F-FLUORODOPA AND PET.
A. Becherer et al University of Vienna, Vienna, Austria.
Although SRS is a suitable first line staging method, FDOPA should be considered as an additional
modality as it performs markedly better in NET visualization than SRS. Especially bone lesions are
detected by FDOPA while for liver metastases, contrast augmented CT is still most sensitive.

ACCURACY OF FDG-PET IN THE EVALUATION OF METASTATIC OR RECURIT~NT
TUMORS WHICH ARE CANDIDATES FOR OCTREOSCAN
.
H. M. Zhuan et al. University of Pennsylvania, Philadelphia, PA.
FDG-PET and octreoscan provide comparable results in patients who are considered optimal candidates for
octreoscan although FDG-PET is slightly more sensitive while octreoscan appears to be slightly more
specific. Considering similarity of costs between these two types of examination, but substantially superior
image quality (whole body vs regional tomographic images), convenience to the patient (2 hours vs 24 hour
for completion of the test), PDG-PET may prove to be more efficient in this setting.

HYBRID IMAGING USING lllIn OCTREOTIDE SPECT/CT IN EVALUATION OF
SOMATOSTATIN RECEPTOR POSITIVE TUMORS.

R. M. Mirtcheva et al, New York Presbyterian Hospital, WeilI Cornell Medical Center, New York, NY.
SPECT/CT fusion imaging significantly improves the diagnostic confidence in interpretation of 111 In
Octreotide SPECT. SPECT/CT has potential to change the diagnostic impression and clinical management,
discriminating physiologic activity from disease and improving the anatomic Localization of findings.

IN-VIVO CHARACTERISATION OF THE FUNCTIONAL ASPECTS OF CARCINOID TUMORS
BY IMAGING SOMATOSTATIN RECEPTORS AND AMINE UPTAKE.

A. M. Quigley et al. Royal Free Hospital, London, United Kingdom; Neuroendocrine Tumor Clinic, Royal
Free Hospital, London, United Kingdom.
Using functional imaging the majority of carcinoid tumors show different affinity for In-ll1 octreotide and
1-123 MIBG, even different lesions within the same patient can show this non-homogenisity. Therefore,
imaging with both agents is essential to fully characterize carcinoid tumor.

SURVIVAL IN PATIENTS WITH NEUROENDOCRINE TUMORS AFTER TREATMENT WITH
[Y-90-DOTA,TYR3] OCTREOTIDE IN A PHASE-1 STUDY.

R. Valkem et al. Rotterdam, Netherlands; UCL St Luc, Brussels, Belgium, H. Lee Mofitt Cancer Center,
Tampa, FL; Novartis Pharmaceuticals Corp, East Hanover, NJ.
Survival after PRRT is good, except in End-Stage patients. These patients can be classified by clinical
criteria. Even in End-Stage patients a therapeutic effect (SD) may improve survival.

TREATING ADVANCED LIVER METASTASES OF NEUROENDOCRINE TUMORS WITH
INTRA-HEAPTIC ARTERY INFUSIONS OF Y-90 LANREOTIDE.

J. R. Buscombe et al. Royal Free Hospital, London, United Kingdom
Objective evidence of tumor growth with stability or shrinkage of previously growing tumor could be seen
in 75% of patients with symptom relief in the same proportion of patients, 63% of patients survived at least
9 months after treatment, There was a low level of toxicity (15%) This treatment or a similar approach
should be considered in all such neuroendocrine tumor patients with extensive liver disease.

In-lll-DTPA-D-Glul-MINIGASTRIN USED FOR THERAPY OF METASTATIC MEDULLARY
THYROID CARCINOMA AND OTHER NEUROENDOCRINE TUMORS: RESULTS OF AN
ONGOING DOSE-ESCALATION STUDY.

M. Gotthardt et al. Philipps-University of Marburg, Marburg, Germany.
To date, our patients did not show nephrotoxicity and only mild hematotoxicity. Thus, the maximum
tolerated dose has not been reached as of yet. Some encouraging responses could be observed.

EVALUATION OF RHENIUM-188 LIPIODOL IN THE TREATMENT OF LIVER CANCER:
EXPERIENCE IN COLOMBIA.

P. Bernal et al. Fundacion Santa Fe Bogota, Bogota, Bogota, Colombia, Memorial Sloan Kettering Cancer
Centre, New York, NY; InternationaI Atomic Energy Agency, Vienna, Vienna, Austria.
Rhenium-188 Lipiodol appears to be a promising and safe radiopharmaceutical for the treatment of liver
cancer. Further studies to establish the efficacy of treatment are being carried out on a large number of
patients through a prospective Phase-II multi-center study.

EFFICACY OF OCTREOSCAN IN DETECTING SOMATOSTATIN RECEPTOR-RICH
MALIGNANCY.

J. Q. Yu et al. University of Pennsylvania, Philadelphia, PA. octreotide scan is a very specific technique for
the evaluation of endocrine tumor with very high PPV. Therefore, a positive octreoscan can be interpreted
with confidence. On the other hand, because of an only moderate NPV, a negative octreoscan should not be
interpreted to represent a disease free state and further studies, such as FDG-PET should be considered.

Return to top of homepage