Improved tumour detection by gastrin receptor scintigraphy in patients with metastasised medullary thyroid carcinoma

Gotthardt, Martin; Béhé, Martin; Beuter, Daniela; Battmann, Anke; Bauhofer, A.; Schurrat, Tino; Schipper, Meike L.; Pollum, Halina; Oyen, Wim J.G.; Behr, Thomas M.

doi:10.1007/s00259-006-0157-8

Cited by 84 publications

(51 citation statements)

References 26 publications

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“…New approaches, such as gastrin receptor scintigraphy, are promising because of the high expression of the cholecystokinin 2 receptor in MTCs (31,32). However, because of the variation in biologic behavior of MTC, the future will reveal what the best imaging approach for these tumors will be.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

Koopmans¹,

Groot²,

Plukker³

et al. 2008

J Nucl Med

111

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Section: Discussionmentioning

confidence: 99%

¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

Koopmans¹,

Groot²,

Plukker³

et al. 2008

J Nucl Med

111

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“…One study also examined the potential therapeutic effects of 90 Y-DTPA-MG0 leading to tumor stabilization at the cost of severe renal toxicity (27). Scintigraphic imaging studies of patients injected with 111 In labeled gastrin-like peptides, or octreotide, showed higher tumor detection rate using gastrin-than somatostatin-receptor images (94 vs. 41%) (35).…”

Section: Introductionmentioning

confidence: 99%

“…These receptors can be targeted with gastrin analogues, e.g., Minigastrin-0 (MG0) (27). Targeting of CCK2/ gastrin receptors with radiolabeled gastrin-like peptides may be a tool for radionuclide imaging and therapy, as previously studied in TT (28)(29)(30)(31) Tc, has previously been studied clinically with promising results (27,29,(33)(34)(35). One study also examined the potential therapeutic effects of 90 Y-DTPA-MG0 leading to tumor stabilization at the cost of severe renal toxicity (27).…”

Section: Introductionmentioning

confidence: 99%

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

et al. 2011

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Abstract.To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177 Lu-octreotate and 111 In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177 Lu-octreotate or 111 In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111 In-MG0. Animals were sacrificed 1-7 days after injection in the 177 Lu-octreotate study and 1 h after injection of 111 In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177 Lu were calculated. There was a specific tumor uptake of either 177 Lu-octreotate or 111 In-MG0. 177 Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177 Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.

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“…There was no Pearson correlation between the scan results and the grade of tumor differentiation, but this aspect appears to deserve more attention. In a similar comparative study of 29 patients with metastatic medullary thyroid cancer, Gotthardt et al (95) found that tumor detection with gastrin receptor scintigraphy was 94.2%, whereas with SRS the detection rate was only 40.7%, correlating with in vitro autography data.…”

Section: Smentioning

confidence: 56%

Radiopeptide Imaging and Therapy in Europe

Ambrosini¹,

Fani²,

Fanti³

et al. 2011

J Nucl Med

183

116

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Receptor targeting with radiolabeled peptides has become an important topic, particularly in nuclear oncology. Strong research efforts are under way in radiopharmaceutical science laboratories and in nuclear medicine departments in Europe. The target receptors belong to the large family of G-proteincoupled receptors. The prototypes of these radiopeptides are based on analogs of somatostatin targeting somatostatin receptor-positive tumors, particularly well-differentiated neuroendocrine tumors. These radiopeptides have an important impact not only on diagnosis but also on targeted radionuclide therapy of these tumors. Besides the registered radiopeptide 111 In-pentetreotide, efficient SPECT tracers labeled with 99m Tc and PET agents based on generator-produced 68 Ga have been developed and used in the clinic. In parallel to the development of diagnostic agents, radiopeptides labeled with the b 2 emitters 90 Y and 177 Lu are also widely used. Because the same chelators and therefore the same conjugates can be used in diagnosis and therapy, they constitute ideal theranostic pairs. This progress is driven not only by scientists and clinicians but also by patient interest groups. New radiopeptides targeting other G-protein-coupled receptors are entering the clinic, among them glucagon-like peptide 1 receptor-targeting molecules. This receptor is overexpressed on literally all benign insulinomas. 111 In-labeled derivatives of the insulinotropic 39-mer peptide exendin-4 were beneficial in the pre-and perioperative localization of these benign lesions. In contrast, lack of localization may indicate malignant insulinoma. The bombesin-and gastrin-releasing peptide receptor family is potentially important because these receptors are overexpressed on major human tumors such as prostate tumors, breast tumors, gastrointestinal stromal tumors, and vessels of ovarian cancer. 99m Tc-labeled peptides for SPECT and 68 Ga-, as well as 64 Cu-labeled agonists or antagonists, have been studied in breast tumors, prostate tumors, gastrointestinal stromal tumors, and gliomas with considerable success. A phase I therapeutic study with a 177 Lu-labeled agonist has been completed. There are not enough clinical data available to reveal the significance of these new modalities in patient care, but several phase I studies are under way in larger patient cohorts using PET agents. Another G-protein-coupled receptor with high overexpression on human tumors is the gastrin/ cholecystokinin-2 receptor. It is overexpressed in more than 90% of cases of medullary thyroid cancer, in small cell lung cancer, and in a subgroup of neuroendocrine tumors. Correlating with in vitro receptor localization using autoradiography of 27 patients with metastasized medullary thyroid cancer, SPECT or planar imaging of these patients resulted in a 95% sensitivity of tumor localization. Finally, another G-protein-coupled receptor is found in brain tumors and peritumoral vessels. Literally all cases of glioblastoma multiforme overexpress the neurokinin type 1 receptor; th...

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Improved tumour detection by gastrin receptor scintigraphy in patients with metastasised medullary thyroid carcinoma

Abstract: GRS had a higher tumour detection rate than SRS and PET in our study. GRS in combination with CT was most effective in the detection of metastatic MTC.

Cited by 84 publications

References 26 publications

¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

Radiopeptide Imaging and Therapy in Europe

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Improved tumour detection by gastrin receptor scintigraphy in patients with metastasised medullary thyroid carcinoma

Abstract: GRS had a higher tumour detection rate than SRS and PET in our study. GRS in combination with CT was most effective in the detection of metastatic MTC.

Cited by 84 publications

References 26 publications

18F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

18F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

Radiopeptide Imaging and Therapy in Europe

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Product

Resources

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¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation

¹⁸F-Dihydroxyphenylalanine PET in Patients with Biochemical Evidence of Medullary Thyroid Cancer: Relation to Tumor Differentiation