The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing h...
The majority of lymphomas of the mucosa-associated lymphoid tissue (MALT)-type arise in the stomach, but extragastric locations are also frequently encountered. Due to previous results indicating that somatostatin receptor (SSTR)-expression distinguishes between gastric and extragastric MALT-type lymphoma, we have initiated a study to evaluate the role of SSTR-scintigraphy for staging and follow-up of patients with extragastric manifestations of MALT-type lymphoma. A total of 30 consecutive patients, including 24 with primary extragastric MALT-type lymphoma, 5 patients with dissemination to extragastric sites (including colon, lung, parotid, ocular adnexa and breast) following an initial gastric MALT-lymphoma and one patient with spread to stomach, lung and lymph nodes following parotid lymphoma were prospectively studied. All patients had histologically verified MALT-type lymphoma: 2 patients had lymphoma presenting in the lung, 9 in the ocular adnexa, 7 had lymphomas in the parotid, 2 patients had disease located in the breast, 3 patients had lymph-node relapse following MALT-type lymphoma of the parotid, the lacrimal gland and the thyroid, and 1 had primary MALT-lymphoma of the liver. All patients underwent SSTR-scintigraphy using 111In-DTPA-D-Phe1-Octreotide (111In-OCT) before initiation of therapy, while 13 also had a second scan after treatment. The results of gamma camera imaging were compared to conventional staging. No positive scans could be obtained in patients with dissemination following gastric lymphoma, while all patients with primary extragastric lymphoma had positive scans at the site of histologically documented involvement before initiation of therapy. In addition, also the patient with secondary spread to stomach, lung and lymph nodes was positive in all documented lymphoma sites. In one patient, focal tracer uptake in projection to the maxillary sinus was documented, which was bioptically verified as inflammation. In the scans performed after therapy, focal tracer accumulation in the left orbit indicated persistance of disease following irradiation in one patient with otherwise negative work-up, which was verified by MRI and biopsy 6 months later. In another patient, a positive scan indicated disease relapse in the lacrimal gland 9 months before clinical verification by means of ultrasound. In one patient, a focus not present in the pretherapeutic scan was found in the ethmoidal sinus, corresponding to a hyperplastic polyp. Both SST-scan as well as CT indicated disease persistance in one case, while negative scans corresponding to complete remission as judged by conventional staging were obtained following therapy in the remaining patients, and absence of relapse has been confirmed for a median follow-up of 2 years. These results indicate that 111In-OCT is an excellent tool for staging and non-invasive therapy-monitoring in extragastric MALT-type lymphomas. These data further confirm our initial finding that gastric MALT-type lymphomas do not express relevant amounts of respective SSTR, and t...
In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F-FDG-PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.
An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BL/ST) and of bone lesion to normal bone (BL/NB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BL/ST ratio in favour of 99mTc-DPD. The BL/NB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.
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