Eur J Nucl Med Mol Imaging (2014) 41:1257–1258 DOI 10.1007/s00259-014-2747-1
LETTER TO THE EDITOR
Comment on: The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer Carlo Aprile & Federica E. Buroni & Lorenzo Lodola & Marco G. Persico
Received: 31 January 2014 / Accepted: 27 February 2014 / Published online: 26 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Sir, The recently published EANM guidelines on breast sentinel lymph node (SLN) [1] are exhaustive and are a useful tool to help the nuclear medicine physician correctly identify SLN in breast cancer. In our opinion one important topic has not been elucidated at all, that is the specific activity (SA) of the administered radiocolloid. More than 50 years ago Iio et al. [2] introduced the concept of phagocytic saturable capacity of the reticuloendothelial system (RES), the maximal rate at which the RES could phagocytize the aggregated albumin particles, regardless of the amount of colloid administered. This critical colloid dose may differ for the distinct reticuloendothelial organs [3]. Therefore, in theory, the clearing capacity of a lymph node is based on a rapidly saturable mechanism due to the limited number of macrophages lining the sinusoid spaces. In clinical application, Gommans et al. [4] demonstrated a fivefold to sixfold increase in SLN count rate employing a SA of 10 MBq/μg albumin nanocolloid (i.e. the maximum SA according to the manufacturer's instructions) in comparison to 2.5 MBq/μg. Although the mechanisms of uptake/metabolism of sulphur and nanocolloid can differ, similar conclusions were drawn by Krynyckyi et al. [5] for sulphur colloid. In contrast, Bourgeois [6] found that following interstitial injection of labelled albumin (Nanocoll) in the lower extremities, injections containing a higher quantity of labelled albumin (200 μg) resulted in higher lymph-node uptake. However, this amount corresponded to about 40 % of the entire Nanocoll® A reply to this comment can be found at doi 10.1007/s00259-014-2750-6. C. Aprile (*) : F. E. Buroni : L. Lodola : M. G. Persico Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, viale Golgi, 19, 27100 Pavia, Italy e-mail: [email protected]
vial, which would appear to be impracticable in routine practice. Furthermore, the analysis was performed not on a single node as in studies of the uptake in the SLN, but on the nodes of the whole inguinal–iliac region, and in this clinical context the tracer would be expected to pass through several nodes of the first and successive tiers in order to visualize all the nodes with the same lymphatic drainage. In contrast to the results of Gommans et al. [4] and Krynyckyi et al. [5], Vermeeren et al. [7] found a better count rate and higher SLN detection rate in prostate cancer using a low SA range (1.12 and 2.25 MBq/μg), but no data are available for the use of higher SA. The use of preparations with high SA has been recommended in the guidelines for the detection of SLN in melanoma [8] and previously by Mariani et al. [9], who in addition pointed out that only a small fraction of the colloidal particles are labelled (5 %), leading to a sort of “non-carrier-free” radiopharmaceutical. In this regard, Gommans et al. [4] calculated that 31 % of total Nanocoll kit particles bind the 99mTc atoms, and using the same method we calculated this parameter from the experimental data on the dimensional distribution and medium particle size reported by Jimenez et al. [10] and by Bergqvist and Strand [11]. This calculation revealed values of 9 % and 0.02 % of 99mTc radiolabelled nanocolloid particles, respectively. In addition, we have found only very few data on radioactivity distribution related to particle size abundance of nanocolloidal human serum albumin (HSA) in the literature. The exact cause for differences in lymph node visualization therefore remains unknown, although SA must be considered differently if the tracer is used for SLN detection, where ideally only one node needs to be visualized, or in lymphoscintigraphy of the extremities where more node tiers need to be visualized. However, this aspect needs attention so
1258
that the best specific radioactivity in nanocolloidal HSA labelling can be chosen in order to improve the mapping of SLN in breast cancer, and is an important topic that should be considered in future EANM guidelines. Conflicts of interest None.
References 1. Giammarile F, Alazraki N, Aarsvold JN, Audisio RA, Glass E, Grant SF, et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer. Eur J Nucl Med Mol Imaging. 2013;40:1932–47. doi:10.1007/ s00259-013-2544-2. 2. Iio M, Wagner Jr HN, Scheffel U, Jabbour B. Studies of the reticuloendothelial system (RES). I. Measurement of the phagocytic capacity of the RES in man and dog. J Clin Invest. 1963;42:417–26. 3. Bergqvist L, Stundberg R, Ryden S, Strand S-E. The “critical colloid dose” in studies of reticuloendothelial function. J Nucl Med. 1987;28:1424–9. 4. Gommans GM, van Dongen A, van der Schors TG, Gommans E, Visser JF, Clarijs WW, et al. Further optimisation of 99mTc-Nanocoll
Eur J Nucl Med Mol Imaging (2014) 41:1257–1258 sentinel node localisation in carcinoma of the breast by improved labelling. Eur J Nucl Med. 2001;28:1450–5. 5. Krynyckyi BR, Zhang Z-Y, Kim CK, Lipszyc H, Mosci K, Machac J. Effect of high specific-activity sulfur colloid preparations on sentinel node count rates. Clin Nucl Med. 2002;27:92–5. 6. Bourgeois P. Scintigraphic investigations of the lymphatic system: the influence of injected volume and quantity of labeled colloidal tracer. J Nucl Med. 2007;48:693–5. 7. Vermeeren L, Muller SH, Meinhardt W, Valdés Olmos RA. Optimizing the colloid particle concentration for improved preoperative and intra-operative image guided detection of sentinel nodes in prostate cancer. Eur J Nucl Med Mol Imaging. 2010;37:1328–34. 8. Chakera AH, Hesse B, Burak Z, Ballinger JR, Britten A, Caracò C, et al. EANM-EORTC general recommendations for sentinel node diagnostics in melanoma. Eur J Nucl Med Mol Imaging. 2009;36: 1713–42. 9. Mariani G, Moresco L, Viale G, Villa G, Bagnasco M, Canavese G, et al. Radioguided sentinel lymph node biopsy in breast cancer surgery. J Nucl Med. 2001;42:1198–215. 10. Jimenez IR, Roca M, Vega E, Garcìa ML, Benitez A, Bajén M, et al. Particle sizes of colloids to be used in sentinel lymph node radiolocalization. Nucl Med Commun. 2008;29:166–72. 11. Bergqvist L, Strand S-E. Autocorrelation spectroscopy for particle sizing and stability tests of radiolabelled colloids. Eur J Nucl Med. 1989;15:641–5.
LETTER TO THE EDITOR
Comment on: The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer Carlo Aprile & Federica E. Buroni & Lorenzo Lodola & Marco G. Persico
Received: 31 January 2014 / Accepted: 27 February 2014 / Published online: 26 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Sir, The recently published EANM guidelines on breast sentinel lymph node (SLN) [1] are exhaustive and are a useful tool to help the nuclear medicine physician correctly identify SLN in breast cancer. In our opinion one important topic has not been elucidated at all, that is the specific activity (SA) of the administered radiocolloid. More than 50 years ago Iio et al. [2] introduced the concept of phagocytic saturable capacity of the reticuloendothelial system (RES), the maximal rate at which the RES could phagocytize the aggregated albumin particles, regardless of the amount of colloid administered. This critical colloid dose may differ for the distinct reticuloendothelial organs [3]. Therefore, in theory, the clearing capacity of a lymph node is based on a rapidly saturable mechanism due to the limited number of macrophages lining the sinusoid spaces. In clinical application, Gommans et al. [4] demonstrated a fivefold to sixfold increase in SLN count rate employing a SA of 10 MBq/μg albumin nanocolloid (i.e. the maximum SA according to the manufacturer's instructions) in comparison to 2.5 MBq/μg. Although the mechanisms of uptake/metabolism of sulphur and nanocolloid can differ, similar conclusions were drawn by Krynyckyi et al. [5] for sulphur colloid. In contrast, Bourgeois [6] found that following interstitial injection of labelled albumin (Nanocoll) in the lower extremities, injections containing a higher quantity of labelled albumin (200 μg) resulted in higher lymph-node uptake. However, this amount corresponded to about 40 % of the entire Nanocoll® A reply to this comment can be found at doi 10.1007/s00259-014-2750-6. C. Aprile (*) : F. E. Buroni : L. Lodola : M. G. Persico Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, viale Golgi, 19, 27100 Pavia, Italy e-mail: [email protected]
vial, which would appear to be impracticable in routine practice. Furthermore, the analysis was performed not on a single node as in studies of the uptake in the SLN, but on the nodes of the whole inguinal–iliac region, and in this clinical context the tracer would be expected to pass through several nodes of the first and successive tiers in order to visualize all the nodes with the same lymphatic drainage. In contrast to the results of Gommans et al. [4] and Krynyckyi et al. [5], Vermeeren et al. [7] found a better count rate and higher SLN detection rate in prostate cancer using a low SA range (1.12 and 2.25 MBq/μg), but no data are available for the use of higher SA. The use of preparations with high SA has been recommended in the guidelines for the detection of SLN in melanoma [8] and previously by Mariani et al. [9], who in addition pointed out that only a small fraction of the colloidal particles are labelled (5 %), leading to a sort of “non-carrier-free” radiopharmaceutical. In this regard, Gommans et al. [4] calculated that 31 % of total Nanocoll kit particles bind the 99mTc atoms, and using the same method we calculated this parameter from the experimental data on the dimensional distribution and medium particle size reported by Jimenez et al. [10] and by Bergqvist and Strand [11]. This calculation revealed values of 9 % and 0.02 % of 99mTc radiolabelled nanocolloid particles, respectively. In addition, we have found only very few data on radioactivity distribution related to particle size abundance of nanocolloidal human serum albumin (HSA) in the literature. The exact cause for differences in lymph node visualization therefore remains unknown, although SA must be considered differently if the tracer is used for SLN detection, where ideally only one node needs to be visualized, or in lymphoscintigraphy of the extremities where more node tiers need to be visualized. However, this aspect needs attention so
1258
that the best specific radioactivity in nanocolloidal HSA labelling can be chosen in order to improve the mapping of SLN in breast cancer, and is an important topic that should be considered in future EANM guidelines. Conflicts of interest None.
References 1. Giammarile F, Alazraki N, Aarsvold JN, Audisio RA, Glass E, Grant SF, et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer. Eur J Nucl Med Mol Imaging. 2013;40:1932–47. doi:10.1007/ s00259-013-2544-2. 2. Iio M, Wagner Jr HN, Scheffel U, Jabbour B. Studies of the reticuloendothelial system (RES). I. Measurement of the phagocytic capacity of the RES in man and dog. J Clin Invest. 1963;42:417–26. 3. Bergqvist L, Stundberg R, Ryden S, Strand S-E. The “critical colloid dose” in studies of reticuloendothelial function. J Nucl Med. 1987;28:1424–9. 4. Gommans GM, van Dongen A, van der Schors TG, Gommans E, Visser JF, Clarijs WW, et al. Further optimisation of 99mTc-Nanocoll
Eur J Nucl Med Mol Imaging (2014) 41:1257–1258 sentinel node localisation in carcinoma of the breast by improved labelling. Eur J Nucl Med. 2001;28:1450–5. 5. Krynyckyi BR, Zhang Z-Y, Kim CK, Lipszyc H, Mosci K, Machac J. Effect of high specific-activity sulfur colloid preparations on sentinel node count rates. Clin Nucl Med. 2002;27:92–5. 6. Bourgeois P. Scintigraphic investigations of the lymphatic system: the influence of injected volume and quantity of labeled colloidal tracer. J Nucl Med. 2007;48:693–5. 7. Vermeeren L, Muller SH, Meinhardt W, Valdés Olmos RA. Optimizing the colloid particle concentration for improved preoperative and intra-operative image guided detection of sentinel nodes in prostate cancer. Eur J Nucl Med Mol Imaging. 2010;37:1328–34. 8. Chakera AH, Hesse B, Burak Z, Ballinger JR, Britten A, Caracò C, et al. EANM-EORTC general recommendations for sentinel node diagnostics in melanoma. Eur J Nucl Med Mol Imaging. 2009;36: 1713–42. 9. Mariani G, Moresco L, Viale G, Villa G, Bagnasco M, Canavese G, et al. Radioguided sentinel lymph node biopsy in breast cancer surgery. J Nucl Med. 2001;42:1198–215. 10. Jimenez IR, Roca M, Vega E, Garcìa ML, Benitez A, Bajén M, et al. Particle sizes of colloids to be used in sentinel lymph node radiolocalization. Nucl Med Commun. 2008;29:166–72. 11. Bergqvist L, Strand S-E. Autocorrelation spectroscopy for particle sizing and stability tests of radiolabelled colloids. Eur J Nucl Med. 1989;15:641–5.
