Myths about inexpediency of carrying out peptide receptor radionuclide diagnostics in patients with neuroendocrine tumors

he disease incidence of neuroendocrine tumors (NET) is increasing every year. Neuroendocrine tumors Grade 1 and 2 have a more favorable prognosis than Grade 3. When we are talking about NET with non-detected initial focus, the 10-year survival rate is 22 % [1]. Therefore, it is necessary to make every effort and use all technical abilities to localize the primary tumor, even in the presence of metastases, because resection of the primary tumor(s) can increase disease-free and overall survival rate. Also, the choice of chemotherapy drug or the appointment of biotherapy may depend on this. Finding tumor localization remains challenging and must involve a combination of radiological, nuclear medicine and endoscopic imaging techniques. There are many different myths about the purpose of nuclear medicine examinations and interpretation of the results in NET patients. And in this article we will try to debunk some of them, using examples from our experience in our center. We choose 111 patients with NET (histologically confimed). All patients underwent scintigraphy of neuroendocrine tumors with 99mTc-EDDA/HYNICTOC (99mTc-Tektrotyd) in the «whole body» mode and additional SPECT or SPECT/CT examination of the chest,abdomen and pelvis.

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Antimicrobial Peptides as Infection Imaging Agents: Better Than Radiolabeled Antibiotics

International Journal of Peptides ◽

10.1155/2012/965238 ◽

2012 ◽

Vol 2012 ◽

pp. 1-19 ◽

Cited By ~ 25

Author(s):

Muammad Saeed Akhtar ◽

Muhammad Babar Imran ◽

Muhammad Afzal Nadeem ◽

Abubaker Shahid

Keyword(s):

Nuclear Medicine ◽

Antimicrobial Peptides ◽

Imaging Techniques ◽

Whole Body ◽

Whole Body Imaging ◽

Nuclear Medicine Imaging ◽

Human Immune System ◽

Large Member ◽

Infection And Inflammation ◽

Radiolabeled Compounds

Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus.

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Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study

JMIR Cancer ◽

10.2196/12849 ◽

2019 ◽

Vol 5 (2) ◽

pp. e12849

Author(s):

Jocelyn Reeders ◽

Vivek Ashoka Menon ◽

Anita Mani ◽

Mathew George

Keyword(s):

Survival Rate ◽

Neuroendocrine Tumors ◽

Primary Tumor ◽

Univariate Analysis ◽

Survival Outcomes ◽

Tumor Site ◽

Primary Tumor Site ◽

Clinical Profiles ◽

Well Differentiated ◽

Related Mortality

Background Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with varying and often indolent clinicobiological characteristics according to their primary location. NETs can affect any organ and hence present with nonspecific symptoms that can lead to a delay in diagnosis. The incidence of NETs is increasing in Australia; data regarding characteristics of NETs were collected from the cancer registry of Hunter New England, Australia. Objective This study aimed to explore the clinical profiles and treatment and survival outcomes of patients with well-differentiated NETs in an Australian population. Methods We reviewed the data of all adult patients who received the diagnosis of NET between 2008 and 2013. The clinicopathological, treatment, and follow-up data were extracted from the local Cancer Clinical Registry. We also recorded the level of remoteness for each patient by matching the patient’s residential postcode to the corresponding Australian Bureau of Statistics 2011 remoteness area category. Univariate analysis was used to find the factors associated with NET-related mortality. Survival analysis was computed. Results Data from 96 patients were included in the study (men: 37/96, 38.5%, and women: 59/96, 61.5%). The median age at diagnosis was approximately 63 years. A higher proportion of patients lived in remote/rural areas (50/96, 52.1%) compared with those living in city/metropolitan regions (46/96, 47.9%). The most common primary tumor site was the gastroenteropancreatic tract, followed by the lung. The factors significantly associated with NET-related mortality were age, primary tumor site, surgical resection status, tumor grade, and clinical stage of the patient. At 5 years, the overall survival rate was found to be 62%, and the disease-free survival rate was 56.5%. Conclusions Older age, advanced unresectable tumors, evidence of metastasis, and higher-grade tumors were associated with poorer outcomes. Lung tumors had a higher risk of NET-related mortality compared with other sites.

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Brain metastases of neuroendocrine tumor with unknown primary location - Case report

Romanian Neurosurgery ◽

10.2478/romneu-2013-0005 ◽

2013 ◽

Vol 20 (2) ◽

pp. 159-165 ◽

Cited By ~ 4

Author(s):

F.M. Brehar ◽

R.M. Gorgan ◽

Angela Neacsu

Keyword(s):

Brain Metastases ◽

Ct Scan ◽

Neuroendocrine Tumor ◽

Neuroendocrine Tumors ◽

Primary Tumor ◽

Whole Body ◽

Facial Paresis ◽

Cerebral Mri ◽

Primary Location ◽

The Brain

Abstract Neuroendocrine tumors are tumors derived from the cells of the neuroendocrine system. The majority of metastases of neuroendocrine tumors occur in liver, lungs and bone. The brain is an uncommon site of metastasize for this type of tumor. The authors of this paper present a case of brain metastases of neuroendocrine tumor with undetermined primary location. The patient, a 35 yearsold man, was admitted in our clinic with headache, nausea, vomiting and a mild right facial paresis. Head CT scan and cerebral MRI identified two lesions: one larger lesion with mixed solid and cystic components located in the left basal ganglia and thalamus and a second cystic lesion located deep in the right parietal lobe. All complementary investigations (including thoracic CT scan and whole-body MRI) failed to reveal the primary tumor location. Due to the high vital-risks associated with the open surgical procedure, the patient and his family chose the less invasive procedure of stereotactic biopsy. Postoperatively the patient had no additional neurologic deficits, presenting only the initial mild right central facial paresis. The result of immunohistochemistry examination was cerebral metastases of neuroendocrine tumor. The patient was directed to the Institute of Oncology Fundeni for further investigations and therapeutically management. In conclusion, even if these are rare tumors which rarely metastasize in the brain, the neurosurgeons should take in consideration this pathology when they examine a patient with multiple cerebral lesions with unknown location of primary tumor.

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Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study (Preprint)

10.2196/preprints.12849 ◽

2018 ◽

Author(s):

Jocelyn Reeders ◽

Vivek Ashoka Menon ◽

Anita Mani ◽

Mathew George

Keyword(s):

Survival Rate ◽

Neuroendocrine Tumors ◽

Primary Tumor ◽

Univariate Analysis ◽

Survival Outcomes ◽

Tumor Site ◽

Primary Tumor Site ◽

Clinical Profiles ◽

Well Differentiated ◽

Related Mortality

BACKGROUND Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with varying and often indolent clinicobiological characteristics according to their primary location. NETs can affect any organ and hence present with nonspecific symptoms that can lead to a delay in diagnosis. The incidence of NETs is increasing in Australia; data regarding characteristics of NETs were collected from the cancer registry of Hunter New England, Australia. OBJECTIVE This study aimed to explore the clinical profiles and treatment and survival outcomes of patients with well-differentiated NETs in an Australian population. METHODS We reviewed the data of all adult patients who received the diagnosis of NET between 2008 and 2013. The clinicopathological, treatment, and follow-up data were extracted from the local Cancer Clinical Registry. We also recorded the level of remoteness for each patient by matching the patient’s residential postcode to the corresponding Australian Bureau of Statistics 2011 remoteness area category. Univariate analysis was used to find the factors associated with NET-related mortality. Survival analysis was computed. RESULTS Data from 96 patients were included in the study (men: 37/96, 38.5%, and women: 59/96, 61.5%). The median age at diagnosis was approximately 63 years. A higher proportion of patients lived in remote/rural areas (50/96, 52.1%) compared with those living in city/metropolitan regions (46/96, 47.9%). The most common primary tumor site was the gastroenteropancreatic tract, followed by the lung. The factors significantly associated with NET-related mortality were age, primary tumor site, surgical resection status, tumor grade, and clinical stage of the patient. At 5 years, the overall survival rate was found to be 62%, and the disease-free survival rate was 56.5%. CONCLUSIONS Older age, advanced unresectable tumors, evidence of metastasis, and higher-grade tumors were associated with poorer outcomes. Lung tumors had a higher risk of NET-related mortality compared with other sites.

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Functional Imaging and Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumor

The Korean Journal of Pancreas and Biliary Tract ◽

10.15279/kpba.2021.26.1.10 ◽

2021 ◽

Vol 26 (1) ◽

pp. 10-14

Author(s):

Keon Wook Kang

Keyword(s):

Computed Tomography ◽

Nuclear Medicine ◽

Neuroendocrine Tumors ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Response To Therapy ◽

Whole Body ◽

Peptide Receptor ◽

Pet Ct

Somatostatin receptors (SSTR) are overexpressed in various tumors including neuroendocrine tumors. In-111 Octreoscan or Ga-68 DOTATOC positron emission tomography/computed tomography (PET/CT) showed these SSTR expressing tumors in whole body of patients. Ga-68 DOTATOC PET/CT has a better sensitivity and resolution than In-111 Octreoscan with single photon emission computed tomography (SPECT)/CT.. The indications of Ga-68 DOTATOC PET/CT are 1) staging: detect sites of primary and metastasis, 2) re-staging: follow-up of patients with known disease to detect residual, recurrent or progressive disease, 3) prognosis & management decisions: determine SSTR status & select patients with SSTR radionuclide therapy, and 4) monitor the response to therapy. Nuclear medicine treatments for neuroendocrine tumors with radioisotope labeling on the somatostatin receptor targeting peptide (peptide receptor radionuclide therapy, PRRT) were conducted in Europe, Australia, and other countries for over 20 years. Eligible patients to be effective to PRRT using Lu-177 DOTATATE can be pre-screened by confirming the expression of somatostatin receptor on tumors using Octreoscan or Ga-68 DOTATOC PET/CT prior to treatment. This pair of molecular targeted treatment and companion diagnostics, so called molecular theranostics makes PRRT a good example for a precision medicine. A multinational clinical trial with the Lu-177 DOTATATE treatment (Lutathera) showed a significant progression free survival over the control group and Ministry of Food and Drug Safety in Korea approved Lutathera. Some doctors are treating patients who are refractory to Lu-177 using Ac-225, an alpha-emitter therapy in Germany and India. The high therapeutic effect of the alpha emitting radionuclides will lead the future of nuclear medicine therapy.

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Whole-Body 11C-5-Hydroxytryptophan Positron Emission Tomography as a Universal Imaging Technique for Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and Computed Tomography

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1938 ◽

2005 ◽

Vol 90 (6) ◽

pp. 3392-3400 ◽

Cited By ~ 221

Author(s):

H. Orlefors ◽

A. Sundin ◽

U. Garske ◽

C. Juhlin ◽

K. Oberg ◽

...

Keyword(s):

Computed Tomography ◽

Positron Emission Tomography ◽

Neuroendocrine Tumors ◽

Primary Tumor ◽

Imaging Technique ◽

Somatostatin Receptor ◽

Emission Tomography ◽

Whole Body ◽

Positron Emission ◽

Receptor Scintigraphy

Neuroendocrine tumors (NETs) can be small and situated almost anywhere throughout the body. Our objective was to investigate whether whole-body (WB) positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) can be used as a universal imaging technique for NETs and to compare this technique with established imaging methods. Forty-two consecutive patients with evidence of NET and a detected lesion on any conventional imaging (six bronchial, two foregut, 16 midgut, and two thymic carcinoids; one ectopic Cushing’s syndrome; four gastrinomas; one insulinoma; six nonfunctioning endocrine pancreatic tumors; one gastric carcinoid, one paraganglioma; and two endocrine-differentiated pancreatic carcinomas) were studied. The WB-11C-5-HTP-PET examinations were compared with WB-computed tomography (CT) and somatostatin receptor scintigraphy (SRS). Tumor lesions were imaged with PET in 95% of the patients. In 58% of the patients, PET could detect more lesions than SRS and CT and equal numbers in 34%, whereas in three cases, SRS or CT showed more lesions. In 84% (16 of 19 patients), PET could visualize the primary tumor compared with 47 and 42% for SRS and CT, respectively. The surgically removed PET-positive primary tumor sizes were 6–30 mm. To conclude, this study indicates that WB-11C-5-HTP-PET can be used as a universal imaging method for detection of NETs. This study also shows that WB-11C-HTP-PET is sensitive in imaging small NET lesions, such as primary tumors, and can in a majority of cases image significantly more tumor lesions than SRS and CT.

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Scintigraphy with 99m Tc-Phosphonate and 67Gallium in Patients Suspected of Primary Bone Tumors

Nuklearmedizin ◽

10.1055/s-0037-1620567 ◽

1982 ◽

Vol 21 (04) ◽

pp. 136-139 ◽

Cited By ~ 2

Author(s):

C.-J. Edeling

Keyword(s):

Soft Tissue ◽

Bone Scintigraphy ◽

Primary Tumor ◽

Bone Tumors ◽

Whole Body ◽

Skeletal Metastases ◽

Malignant Bone Tumors ◽

67Ga Scintigraphy ◽

Primary Bone Tumors ◽

Primary Bone

Whole-body scintigraphy with both 99mTc-phosphonate and 67Ga was performed on 92 patients suspected of primary bone tumors. In 46 patients with primary malignant bone tumors, scintigraphy with 99mTc-phosphonate disclosed the primary tumor in 44 cases and skeletal metastases in 11, and 67Ga scintigraphy detected the primary tumor in 43 cases, skeletal metastases in 6 cases and soft-tissue metastases in 8 cases. In 25 patients with secondary malignant bone tumors, bone scintigraphy visualized a single lesion in 10 cases and several lesions in 15 cases, and 67Ga scintigraphy detected the primary tumor in 17 cases, skeletal metastases in 17 cases and soft-tissue metastases in 9 cases. In 21 patients with benign bone disease positive uptake of 99mTc-phosphonate was recognized in 19 cases and uptake of 67Ga in 17 cases. It is concluded that bone scintigraphy should be used in patients suspected of primary bone tumors. If malignancy is suspected, 67Ga scintigraphy should be performed in addition.

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A Simple Method for the Evaluation of Internal Doses in Nuclear Medicine

Nuklearmedizin ◽

10.1055/s-0038-1624857 ◽

1974 ◽

Vol 13 (02) ◽

pp. 193-206

Author(s):

L. Conte ◽

L. Mombelli ◽

A. Vanoli

Keyword(s):

Nuclear Medicine ◽

Close Agreement ◽

Whole Body ◽

Simple Method ◽

Rapid Estimation ◽

Absorbed Doses ◽

The Mean ◽

The Individual ◽

Estimation Of Risk

SummaryWe have put forward a method to be used in the field of nuclear medicine, for calculating internally absorbed doses in patients. The simplicity and flexibility of this method allow one to make a rapid estimation of risk both to the individual and to the population. In order to calculate the absorbed doses we based our procedure on the concept of the mean absorbed fraction, taking into account anatomical and functional variability which is highly important in the calculation of internal doses in children. With this aim in mind we prepared tables which take into consideration anatomical differences and which permit the calculation of the mean absorbed doses in the whole body, in the organs accumulating radioactivity, in the gonads and in the marrow; all this for those radionuclides most widely used in nuclear medicine. By comparing our results with dose obtained from the use of M.I.R.D.'s method it can be seen that when the errors inherent in these types of calculation are taken into account, the results of both methods are in close agreement.

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Aktivitätskonzentration der vom Personal einer Radiojodtherapiestation eingeatmeten Luft

Nuklearmedizin ◽

10.1055/s-0038-1628879 ◽

1987 ◽

Vol 26 (03) ◽

pp. 143-146 ◽

Cited By ~ 2

Author(s):

H. Fill ◽

M. Oberladstätter ◽

J. W. Krzesniak

Keyword(s):

Nuclear Medicine ◽

Length Of Stay ◽

Activity Concentration ◽

Threshold Value ◽

Whole Body ◽

Therapeutic Activity ◽

External Radiation ◽

Oral Application ◽

Exhaled Air ◽

The Mean

The mean activity concentration of1311 during inhalation by the nuclear medicine personnel was measured at therapeutic activity applications of 22 GBq (600 mCi) per week. The activity concentration reached its maximum in the exhaled air of the patients 2.5 to 4 hours after oral application. The normalized maximum was between 2 • 10−5 and 2 • 10−3 Bq-m−3 per administered Bq. The mean activity concentration of1311 inhaled by the personnel was 28 to 1300 Bq-m−3 (0.8 to 35 nCi-rrf−3). From this the1311 uptake per year was estimated to be 30 to 400 kBq/a (x̄ = 250, SD = 50%). The maximum permitted uptake from air per year is, according to the German and Austrian radiation protection ordinances 22/21 µiCi/a (= 8 • 105 Bq/a). At maximum 50% and, on the average, 30% of this threshold value are reached. The length of stay of the personnel in the patient rooms is already now limited to such an extent that 10% of the maximum permissible whole-body dose for external radiation is not exceeded. Therefore, increased attention should be paid also to radiation exposure by inhalation.

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Immunszintigraphie mit 111ln-DTPA-markierten monoklonalen Antikörpern: Vergleich zwischen ECT und planarer Szintigraphie

Nuklearmedizin ◽

10.1055/s-0038-1628900 ◽

1987 ◽

Vol 26 (06) ◽

pp. 258-262

Author(s):

J. Happi ◽

R. P. Baum ◽

J. Frohn ◽

B. Weimer ◽

A. Halbsguth ◽

...

Keyword(s):

Imaging Techniques ◽

Diagnostic Procedures ◽

Undifferentiated Carcinoma ◽

Whole Body ◽

Acquisition Time ◽

Planar Imaging ◽

Primary Tumors ◽

Intraindividual Comparison ◽

Single Detector ◽

Increased Sensitivity

The present study was done in order to examine if the use of111ln-DTPA- labeled MAb fragments in place of 131l-labeled MAb fragments increases the sensitivity of tomographic immunoscintigraphy to reach the level of that of planar imaging techniques. In 11 patients with various primary tumors, local recurrences or metastases [colorectal carcinoma (n = 7), ovarian carcinoma (n = 2), papillary thyroid carcinoma (n = 1), undifferentiated carcinoma of the lung (n = 1)], immunoscintigraphy (IS) was carried out using 111ln-DTPA- labeled F(ab’)2 fragments of various MAbs (anti-CEA, OC 125, anti-hTG) and planar and tomographic imaging were compared intraindividually. By conventional diagnostic procedures, the presence of a tumor mass was confirmed (transmission computer tomography, ultrasound) or verified (131l whole-body scintigraphy, histology) in all cases. Immunoscintigraphy was positive in 9 out of 11 cases by ECT and in 10 out of 11 cases by planar imaging. When using 111 In-labeled MAb fragments, intraindividual comparison of ECT and planar imaging resulted in a similar sensitivity. The increased sensitivity of ECT using this tracer in contrast to 131l-labeled MAb fragments may be attributed to the fact that the physical properties of111 In are much more suitable for the gamma cameras most commonly used (single detector, 3/8” crystal); using 111 In-labeled MAb fragments, count rates sufficient for ECT can be obtained within a reasonable acquisition time. This allows to combine IS with the advantages of ECT regarding tumour localization and prevention of artefacts due to superposition of background.

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