111In-labelled somatostatin analogues in a rat tumour model: somatostatin receptor status and effects of peptide receptor radionuclide therapy

Capello, Astrid; Krenning, Eric P.; Bernard, Bert F.; Reubi, Jean–Claude; Breeman, W. A. P.; Jong, Marcel de

doi:10.1007/s00259-005-1877-x

Cited by 50 publications

(28 citation statements)

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“…When 111 In-labeled analogs were applied during PRRT, less therapeutic benefit was generated (3,4), probably because of the short range of the high linear energy transfer of Auger electrons, without cross-fire effect. In line with these observations, 111 Inoctreotate was more efficacious for the treatment of smaller, than larger, tumors in CA20948 tumor-bearing rats (5).…”

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confidence: 54%

Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Melis¹,

Vegt²,

Konijnenberg³

et al. 2010

J Nucl Med

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We determined the renal radiation dose of a series of 111 Inlabeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed. Methods: Wild-type and megalin-deficient mice were imaged repeatedly at 3-to 6-wk intervals to quantify renal retention after injection of 40-50 MBq of 111 In-diethylenetriaminepentaacetic acidlabeled peptides (octreotide, exendin, octreotate, neurotensin, and minigastrin analogs), and the absorbed kidney radiation doses were estimated. Body weight, renal function parameters, and renal histology were determined at 16-20 wk after the first scan and compared with those in naive animals. Results: Because of high renal retention, 111 In-diethylenetriaminepentaacetic acid-exendin-4 scans resulted in a 70-Gy kidney radiation dose in wild-type mice. Megalin-deficient kidneys received 20-40 Gy. The other peptides resulted in much lower renal doses. Kidney function monitoring indicated renal damage in imaged animals. Conclusion: Micro-SPECT enables longitudinal studies in 1 animal. However, long-term nephrotoxic effects may be induced after high renal radiation doses, even with 111 In-labeled radiotracers.

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confidence: 54%

Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Melis¹,

Vegt²,

Konijnenberg³

et al. 2010

J Nucl Med

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“…Exposure to low amounts of 177 Lu-octreotate gave a twofold higher concentration of 111 In-octreotide in the tumour tissue with no increased concentration in normal tissues. Radiation-induced SSTR upregulation has been reported in other in vitro and in vivo models [41,46,89]. …”

Section: Methods To Increase the Treatment Effect On Tumour Tissuementioning

confidence: 97%

“…The optimal time intervals and number of fractions using radiolabelled SS analogues are still to be defined. Several studies in CA20948-bearing rats using different radiolabelled SS analogues have presented favourable therapy results using fractionation [43,44,45,46]. …”

Section: General Methods Including Individualizationmentioning

confidence: 99%

“…Therapy has been suggested/performed in animals and patients using SS analogues labelled with various radionuclides, e.g. the Auger and conversion electron emitters 111 In and 103m Rh (low electron energy) [46,72], the β-emitters 177 Lu, 153 Sm, and 161 Tb (medium electron energy) [23,24,26,42,44,51,73,74,75] and 90 Y, and 188 Re (high electron energy) [76,77,78] and the α-particle emitters 225 Ac, 211 At and 213 Bi [66,67,68,79]. For radionuclides with a higher electron energy and thus longer range, the absorbed fraction/dose in small tumours will be lower than in larger tumours and tissue surrounding the tumours will be more highly exposed.…”

Section: General Methods Including Individualizationmentioning

confidence: 99%

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Radionuclide Therapy via SSTR: Future Aspects from Experimental Animal Studies

Forssell-Aronsson¹,

Spetz²,

Ahlman

2012

Neuroendocrinology

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There is need for better therapeutic options for neuroendocrine tumours. The aim of this review was to summarize results of experimental animal studies and raise ideas for future radionuclide therapy based on high expression of somatostatin (SS) receptors by many neuroendocrine tumours. In summary, one of the major options is individualized treatment for each patient, including choice of SS analogues, radionuclides and treatment schedules. Other options are methods to increase the treatment effect on tumour tissue (increasing tumour uptake and retention by upregulation of receptor expression and avoiding saturation of receptor binding), methods to increase the tumour tissue response (by choice of radionuclides, SS analogues or combined therapies), and methods to reduce side effects (diminished uptake and retention in critical organs and reduced normal tissue response). Furthermore, combination therapy with other radiopharmaceuticals, cytotoxic drugs or radiosensitizers can be considered to enhance the effects of radiolabelled SS analogues.

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“…It was shown to strongly express sstr 2 at the cell surface; this expression was quantitated, and the binding of sstr analogs in vivo was shown to be receptor-specific (9,10). In addition, this cell line internalizes several 111 In-labeled somatostatin analogs and was used previously to demonstrate the effect of PRRT (11).…”

Section: Animals and Tumor Inoculationmentioning

confidence: 99%

Effect of Interferon-α Treatment on [⁶⁸Ga-DOTA,Tyr3,Thre8]Octreotide Uptake in CA20948 Tumors: A Small-Animal PET Study

Hanin¹,

Pauwels²,

Bol³

et al. 2011

J Nucl Med

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In peptide receptor radionuclide therapy of neuroendocrine tumors, improvements have been made by increasing the affinity for receptors and by protecting critical organs (e.g., kidneys). However, tumor parameters involved in radiopeptide uptake are still under investigation. Interferon-a (IFNa) is used as biotherapy for neuroendocrine tumors. Several mechanisms of action are described, but the potential effect of IFNa on tumor uptake of labeled peptide has not been studied in vivo yet. Methods: Twenty-six male CA20948 tumor-bearing Lewis rats were imaged before and during IFNa treatment using quantitative small-animal PET with [ 68 Ga-DOTA,Tyr 3 ,Thre 8 ]octreotide. Imaging was performed at days 0, 3, and 7. Animals were divided into 3 groups according to the treatment: control (injected daily with saline), half (4 d of IFNa treatment from day 0 to day 3, then saline), and full (7 d of IFNa). A daily dose of IFNa (1.5 mIU) was administered subcutaneously. Quantitative PET results are expressed as percentage injected dose per cm 3 and normalized to baseline (day 0) values. Tumor size was monitored by PET and caliper measurements. Results: Gross tumor uptake and tumor volumes increased in all groups over the 7-d period. On day 3, mean 6 SD ratios to day 0 were 1.2 6 0.2, 1.3 6 0.5, and 1.2 6 0.4, respectively, for control, half, and full groups. On day 7, respective values were 1.1 6 0.2, 1.3 6 0.6, and 1.5 6 0.4. At day 3, a comparison among groups showed no statistically significant difference. At day 7, the full group showed a significantly higher ratio in activity concentration than the control group (P 5 0.021). A good correlation was found between tumor volumes assessed by small-animal PET and caliper measurements (R 5 0.89, P , 0.0001). Conclusion: As expected, over a period of 7 d, both tumor volumes and radiopeptide uptake increased in all animals. However, the activity concentration increased significantly more at day 7 in animals treated for 7 d with IFNa, compared with controls. This is the first, to our knowledge, in vivo indication that IFNa is able to increase tumor uptake of the labeled analog in a small-animal model of neuroendocrine tumors. The mechanisms underlying this effect (flow, vascular permeability, receptor upregulation) remain unknown and need to be further investigated.

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111In-labelled somatostatin analogues in a rat tumour model: somatostatin receptor status and effects of peptide receptor radionuclide therapy

Cited by 50 publications

References 17 publications

Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Radionuclide Therapy via SSTR: Future Aspects from Experimental Animal Studies

Effect of Interferon-α Treatment on [⁶⁸Ga-DOTA,Tyr3,Thre8]Octreotide Uptake in CA20948 Tumors: A Small-Animal PET Study

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111In-labelled somatostatin analogues in a rat tumour model: somatostatin receptor status and effects of peptide receptor radionuclide therapy

Cited by 50 publications

References 17 publications

Nephrotoxicity in Mice After Repeated Imaging Using 111In-Labeled Peptides

Nephrotoxicity in Mice After Repeated Imaging Using 111In-Labeled Peptides

Radionuclide Therapy via SSTR: Future Aspects from Experimental Animal Studies

Effect of Interferon-α Treatment on [68Ga-DOTA,Tyr3,Thre8]Octreotide Uptake in CA20948 Tumors: A Small-Animal PET Study

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Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Nephrotoxicity in Mice After Repeated Imaging Using ¹¹¹In-Labeled Peptides

Effect of Interferon-α Treatment on [⁶⁸Ga-DOTA,Tyr3,Thre8]Octreotide Uptake in CA20948 Tumors: A Small-Animal PET Study