Salvage Therapy with <sup>177</sup>Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors

Essen, Marc van; Krenning, Eric P.; Kam, Boen L.R.; Herder, Wouter W. de; Feelders, Richard A; Kwekkeboom, Dik J.

doi:10.2967/jnumed.109.068957

Cited by 115 publications

(76 citation statements)

References 13 publications

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“…However, the current data suggest that 99m Tc-MAG3 renography is a more sensitive method to quantify loss of function of cortical proximal tubules than 99m Tc-DMSA scintigraphy after PRRT. Unaffected 99m Tc-MAG3 renography is one of the inclusion criteria before 90 Y-or 177 Lu-based PRRT and is also used during follow-up at 1 center (12,35), besides common glomerular filtration rate markers used at other medical centers (8,14). Although further clinical validation is warranted, the introduction of routine 99m Tc-MAG3 renography might be considered at more PRRT centers, especially in patients with compromised renal function.…”

Section: Discussionmentioning

confidence: 99%

“…Although further clinical validation is warranted, the introduction of routine 99m Tc-MAG3 renography might be considered at more PRRT centers, especially in patients with compromised renal function. Also, patients receiving extra cycles of PRRT (7,8) are appropriate candidates for 99m Tc-MAG3 follow-up when doses exceed the accepted safe limit of 23-27 Gy absorbed kidney radiation dose, adapted from external beam radiation, or the 37-to 45-Gy limit of the biologically equivalent dose on the kidney, taking into account the kidney mass and nonuniform localization of renal radioactivity (36,37). The application of renal imaging using 99m Tc-DMSA or 99m Tc-MAG3 can be extended to follow up renal proximal tubule function in other diseases when the kidney is the organ at risk (26,38).…”

Section: Discussionmentioning

confidence: 99%

“…However, partial reabsorption of the radiopeptides in the kidneys may lead to long-term nephrotoxic effects, especially when 90 Y-labeled analogs are administered (5,6). Recent developments to further improve tumor response rates include salvage therapy and combined therapy with both 90 Y-and 177 Lu-labeled radiopeptides, supporting the need for kidney protection (7)(8)(9). Today, coinfusion of lysine and arginine during PRRT is a protective measure in the clinic, resulting in a 35%-40% reduction of the kidney radiation dose (10)(11)(12), also found in preclinical animal models (13).…”

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confidence: 99%

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Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy

Melis¹,

Swart²,

Visser³

et al. 2010

J Nucl Med

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High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with b-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal radiation dose. In rat PRRT studies, renal protection by the coadministration of lysine was confirmed by histologic examination of kidney specimens indicating nephrotoxicity. In the current study, we investigated dedicated small-animal SPECT/CT renal imaging in rats to monitor renal function in vivo during follow-up of PRRT, with and without lysine. Methods: The following 3 groups of rats were imaged using a multipinhole SPECT/CT camera: controls (group 1) and rats at more than 90 d after therapy with 460 MBq (15 mg) of 177 Lu-DOTA-Tyr 3 -octreotate without (group 2) or with (group 3) a 400-mg/kg lysine coinjection as kidney protection (n $ 6 per group). At 90 and 140 d after therapy, static kidney scintigraphy was performed at 2 h after injection of 25 MBq of 99m Tc-dimercaptosuccinic acid ( 99m Tc-DMSA). In addition, dynamic dual-isotope renography was performed using 50 MBq of 111 In-diethylenetriaminepentaacetic acid ( 111 In-DTPA) and 50 MBq of 99m Tc-mercaptoacetyltriglycine ( 99m Tc-MAG3) at 100-120 d after therapy. Results: 111 In-DTPA and 99m Tc-MAG3 studies revealed a time-activity pattern comparable to those in patients, with a peak at 2-6 min followed by a decline of renal radioactivity. Reduced 111 In-DTPA, 99m Tc-MAG3, and 99m Tc-DMSA uptake indicated renal damage in group 2, whereas group 3 showed only a decrease of 99m Tc-MAG3 peak activity. These results indicating nephrotoxicity in group 2 and renal protection in group 3 correlated with levels of urinary protein and serum creatinine and urea and were confirmed by renal histology. Conclusion: Quantitative dynamic dual-isotope imaging using both 111 In-DTPA and 99m Tc-MAG3 and static 99m Tc-DMSA imaging in rats is feasible using small-animal SPECT, enabling longitudinal monitoring of renal function. 99m Tc-MAG3 renography, especially, appears to be a more sensitive marker of tubular function after PRRT than serum chemistry or 99m Tc-DMSA scintigraphy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy

Melis¹,

Swart²,

Visser³

et al. 2010

J Nucl Med

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“…The in vivo applications of key 177 Lu radiopharmaceuticals for a variety of therapeutic procedures include peptide receptor radionuclide therapy [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], bone pain palliation [27][28][29][30][31][32][33], radiation synovectomy [34][35][36][37][38][39] and radioimmonutherapy [40][41][42][43][44][45][46]. There is a steadily expanding list of 177 Lu-labeled radiopharmaceuticals that is currently being evaluated at the preclinical research or at product development stages; these may potentially be used in vivo in humans for evaluation for radionuclide therapy [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

Dash

Pillai²,

Knapp

2015

Nucl Med Mol Imaging

251

166

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Background: This review provides a comprehensive summary of the production of 177 Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177 Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. Methods: While both "direct" and "indirect" reactor production routes offer the possibility for sustainable 177 Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. Results: This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. Conclusion: A broad understanding and discussion of the issues associated with 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments.

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“…Their data analysis demonstrated a median TTP after regular therapy of 27 months [12]. In four patients, the intended cumulative dose of 14.8 GBq in two cycles was not achieved (two had progressive disease, two had long-lasting thrombocytopenia).…”

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confidence: 99%

How smart is peptide receptor radionuclide therapy of neuroendocrine tumors especially in the salvage setting? The clinician’s perspective

Prasad

Brenner

Modlin

2013

Eur J Nucl Med Mol Imaging

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In the recent past there has been a substantial growth in the understanding of cancer biology with a consequent opening of a Pandora's box of scientific knowledge and advance in the biological perception of the disease. Paradoxically, this indepth, sun-burst-like knowledge has fogged the several established management protocols rather than clearing the doubts. The 'knowledge' that the hitherto established and proven therapeutics do not only target cancer cells but also 'normal' cells has shifted the attention more onto toxicity.To overcome the toxicity related to the 'generalized' treatment approach medical scientists across the world have gleefully (and possibly gullibly) accepted targeted therapy and the 'theranostic concept'. This evolved approach should eventually, supposedly, tackle the intelligent cancer cells which have successfully challenged 'Darwin's Theory of Evolution' by replacing the normal 'chosen' cells of the best creation and evolved creature of nature. Paradoxically survival of the fittest in this instance leads to extinction of the organism! This has generated a new intellectual theocracy whereby new knowledge has been embraced with almost religious zeal and rigorous assessment diminished in the face of fervor as we seek to reverse a biological Darwinian conundrum. As a consequence a note of caution needs to be placed here because the knowledge of the scientific medical community about neoplasia is juvenile, whereas the cancer cells, by the time they are diagnosed, are evolved and are up to 40 years old [1]. In effect they are the adults in the evolutionary cascade, and thereby not only challenging but also winning the natural selection process which decrees that "growth and spread is to the strongest". In consideration of such (very old) philosophy, direct implementation of the promising but not matured theranostic concept in a patient with aggressive cancer, with a relatively shorter life expectancy, might not have a significant adverse influence on an already poor quality of life. The problem however achieves a different degree of proportionality when the concept is translated to the treatment of an indolent tumor associated with a relatively good overall survival following the initial diagnosis. Neuroendocrine tumors (NETs) are a group of such tumors, whose incidence and prevalence appear to be increasing at an alarming rate, partially due to highly advanced diagnostic methods and raised awareness [2].Nuclear medicine is the first exponent of the theranostic concept dating back to early 1950s. The classical example is the use of radioiodine for diagnosis and therapy of various benign and malignant thyroid diseases targeting the thyroid cell sodium iodine transporters. A similar analogy is the identification of the overexpression of somatostatin receptors on NETs. This has enabled nuclear medicine physicians to deal with the complex and heterogeneous tumor by addressing the neoplastic overexpression of particular subclasses of somatostatin receptor. Thus somatostatin receptor-based molecul...

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Salvage Therapy with ¹⁷⁷Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors

Cited by 115 publications

References 13 publications

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

How smart is peptide receptor radionuclide therapy of neuroendocrine tumors especially in the salvage setting? The clinician’s perspective

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Salvage Therapy with 177Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors

Cited by 115 publications

References 13 publications

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After 177Lu-Labeled Tyr3-Octreotate Radionuclide Therapy

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After 177Lu-Labeled Tyr3-Octreotate Radionuclide Therapy

Production of 177Lu for Targeted Radionuclide Therapy: Available Options

How smart is peptide receptor radionuclide therapy of neuroendocrine tumors especially in the salvage setting? The clinician’s perspective

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Product

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Salvage Therapy with ¹⁷⁷Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy

Dynamic and Static Small-Animal SPECT in Rats for Monitoring Renal Function After ¹⁷⁷Lu-Labeled Tyr³-Octreotate Radionuclide Therapy