Para-[123I]iodo-L-phenylalanine in patients with pancreatic adenocarcinoma

D. Hellwig; E. Gouverneur; A. Schaefer; J. Raedle; M. Menges; C.-M. Kirsch; S. Samnick

doi:10.3413/nukmed-0152

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2008; 47(05): 220-224
DOI: 10.3413/nukmed-0152

Original Article

Schattauer GmbH

Para-[¹²³I]iodo-L-phenylalanine in patients with pancreatic adenocarcinoma

Tumour uptake, whole-body kinetics, dosimetryPara-[¹²³I]Iod-L-phenylalanin bei Patienten mit Adenokarzinom des PankreasTumorale Aufnahme, Ganzkörperkinetik und Dosimetrie

Authors

D. Hellwig

¹Departments of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany
E. Gouverneur

¹Departments of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany
A. Schaefer

¹Departments of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany
J. Raedle

²Departments of Internal Medicine II (Gastroenterology), Saarland University Medical Center, Homburg, Germany
M. Menges

²Departments of Internal Medicine II (Gastroenterology), Saarland University Medical Center, Homburg, Germany
C.-M. Kirsch

¹Departments of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany
S. Samnick

¹Departments of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany

Abstract

Summary

Recently, p-[¹²³I]iodo-L-phenylalanine (IPA) was clinically validated for brain tumour imaging. Preclinical studies demonstrated uptake of IPA into pancreatic adenocarcinoma suggesting its diagnostic application in patients with pancreatic tumours. The aim was to study the tumour uptake of IPA in patients with pancreatic adenocarcinoma and to analyse its biodistribution and dosimetry to assess the radiation dose resulting from its diagnostic use. Patients, methods: Seven patients with pancreatic adenocarcinoma underwent whole-body scintigraphies and SPECT up to 24 h after administration of 250 MBq of IPA. Tumour uptake of IPA was assessed visually. Time activity curves and the corresponding residence times were determined for whole-body, kidneys, liver, spleen, lung, heart content, brain, and testes. Mean absorbed doses for various organs and the effective dose were assessed based on the MIRD formalism using OLINDA/EXM. Results: IPA exhibited no accumulation in proven manifestations of pancreatic adenocarcinomas. IPA was exclusively eliminated by the urine and showed a delayed clearance from blood. Residence times were 0.26 ± 0.09 h for kidneys, 0.38 ± 0.19 h for liver, 0.15 ± 0.07 h for spleen, 0.51 ± 0.20 h for lungs, 0.22 ± 0.07 h for heart content, 0.11 ± 0.05 h for brain, 0.014 ± 0.005 h for testes and 6.4 ± 2.2 h for the remainder. The highest absorbed doses were determined in the urinary bladder wall and in the kidneys. According to the ICRP 60 the effective dose resulting from 250 MBq IPA was 3.6 ± 0.7 mSv. Conclusion: Para-[¹²³I]iodo-L-phenylalanine can be used in diagnostic nuclear medicine with acceptable radiation doses. Besides its proven validity for brain tumour imaging, IPA does not appear to be suitable as tracer for pancreatic cancer.

Zusammenfassung

Kürzlich wurde IPA (p-[¹²³I]Iod-L-phenylalanin) klinisch validiert für die Diagnostik hirneigener Tumoren. Präklinische Studien zeigten eine erhöhte Aufnahme von IPA in Adenokarzinomen des Pankreas, sodass der diagnostische Einsatz bei Patienten mit Pankreaskarzinomen vorgeschlagen wurde. Ziel dieser Arbeit war es, erstmals die tumorale Aufnahme von IPA bei Patienten mit Adenokarzinomen des Pankreas zu untersuchen, die Biodistribution und Dosimetrie von IPA zu analysieren sowie die aus der diagnostischen Anwendung resultierende Strahlenexposition zu erfassen. Patienten, Methoden: Bei sieben Patienten mit Adenokarzinomen des Pankreas wurden Ganzkörperszintigraphien und SPECT-Aufnahmen bis zu 24 Stunden nach intravenöser Applikation von 250 MBq IPA angefertigt. Die tumorale Aufnahme von IPA wurde visuell beurteilt. Zeit- Aktivitätskurven und resultierende Verweilzeiten wurden für den Ganzkörper, Nieren, Leber, Milz, Lunge, Herzinhalt, Gehirn und Hoden gemessen und berechnet. Die mittlere absorbierte Dosis für verschiedene Organe und die effektive Dosis wurden nach dem MIRD-Formalismus mittels OLINDA/ EXM ermittelt. Ergebnisse: IPA zeigte keine erhöhte Aufnahme in bekannte Manifestationen von Adenokarzinomen des Pankreas. Die Elimination von IPA erfolgte ausschließlich renal mit einer verzögerten Clearance aus dem Blut. Die Verweilzeiten waren 0,26±0,09 h für die Nieren, 0,38±0,19 h für die Leber, 0,15±0,07 h für die Milz, 0,51±0,20 h für die Lunge, 0,22±0,07 h für den Herzinhalt, 0,11±0,05 h für das Gehirn, 0,014±0,005 h für die Hoden und 6,4±2,2 h für den Restkörper. Die höchsten Organdosen ergaben sich für Harnblasenwand und Nieren. Gemäß ICRP 60 resultiert aus der Anwendung von 250 MBq IPA eine effektive Dosis von 3,6±0,7 mSv. Schlussfolgerung: IPA kann in der diagnostischen Nuklearmedizin mit einer vertretbaren Strahlenexposition angewendet werden. Im Gegensatz zur klinisch validierten Anwendung bei der Diagnostik hirneigener Tumoren eignet sich IPA nicht zur Darstellung von Adenokarzinomen des Pankreas.

Keywords

Radiopharmaceuticals - amino acids - pancreatic adenocarcinoma - radiation dosimetry

Schlüsselwörter

Radiopharmaka - Aminosäuren - Pankreas-Adenokarzinom - Dosimetrie

Full Text

References

References
1 Chari ST. Detecting early pancreatic cancer: problems and prospects. Semin Oncol 2007; 34: 284-294.
2 Cloutier RJ, Smith SA, Watson EE. et al. Dose to the fetus from radionuclides in the bladder. Health Phys 1973; 25: 147-161.
3 Dey HM, Seibyl JP, Stubbs JB. et al. Human biodistribution and dosimetry of the SPECT benzodiazepine receptor radioligand iodine-123-io- mazenil. JNucl Med 1994; 35: 399-404.
4 Diederichs CG, Staib L, Vogel J. et al. Value and limitations of ¹⁸F-fluorodeoxyglucose-positron- emission tomography with preoperative evaluation of patients with pancreatic masses. Pancreas 2000; 20: 109-116.
5 Hellwig D, Ketter R, Romeike BF. et al. Validation of brain tumour imaging with p-[¹²³I]iodo- L-phenylalanine and SPECT. Eur J Nucl Med Mol Imaging 2005; 32: 1041-1049.
6 Hellwig D, Menges M, Schneider G. et al. Radio- iodinated phenylalanine derivatives to image pancreatic cancer: a comparative study with [¹⁸F]fluoro-2-deoxy-d-glucose in human pancreatic carcinoma xenografts and in inflammation models. Nucl Med Biol 2005; 32: 137-145.
7 Hudson HM, Larkin RS. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 1994; 13: 601-609.
8 International Commission on Radiological Protection. 1990 Recommendations. ICRP Publication 60 ed. New York: Pergamon Press; 1991
9 Linder S, Bostrom L, Nilsson B. Pancreatic carcinoma incidence and survival in Sweden in 1980-2000: A population-based study of 16758 hospitalized patients with special reference to different therapies. Eur J Surg Oncol 2007; 33: 616-622.
10 Loevinger R, Budinger TF, Watson EE. MIRD Primer for Absorbed Dose Calculations Revised. New York: Society of NuclearMedicine; 1991
11 Macfarlane D, Gonin J, Wieland D. et al. Successful and unsuccessful approaches to imaging carci- noids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue. Eur JNucl Med 1996; 23: 131-140.
12 Reske SN, Kotzerke J. FDG-PET for clinical use. Results of the 3rd German Interdisciplinary Consensus Conference, "Onko-PET III", 21 July and 19 September 2000. Eur J Nucl Med 2001; 28: 1707-1723.
13 Romeike BF, Hellwig D, Heimann A. et al. Action and efficacy of p-[¹³¹I]iodo-L-phenylalanine on primary human glioma cell cultures and rats with C6-gliomas. Anticancer Res 2004; 24: 3971-3976.
14 Samnick S, Hellwig D, Bader JB. et al. Initial evaluation of the feasibility of single photon emission tomography with p-[¹²³I]iodo-L-pheny- lalanine for routine brain tumour imaging. Nucl Med Comm 2002; 23: 121-130.
15 Samnick S, Romeike BF, Kubuschok B. et al. p-[¹²³I]iodo-L-phenylalanine for detection ofpancreatic cancer: basic investigations of the uptake characteristics in primary human pancreatic tumour cells and evaluation in in vivo models of human pancreatic adenocarcinoma. Eur J Nucl Med Mol Imaging 2004; 31: 532-541.
16 Samnick S, Schaefer A, Siebert S. et al. Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine- 123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells. Nucl Med Biol 2001; 28: 13-23.
17 Snyder WS, Ford MR, Warner GG. et al. “S,” absorbed dose per unit cumulated activity for selected radionuclides and organs. MIRD Pamphlet No. 11. New York: The Society of Nuclear Medicine; 1975
18 Sorensen JA. Quantitative measurement of radioactivity in vivo by whole-body counting. In: Hine GJ. et al. (eds) Instrumentation in nuclear medicine. New York: Academic Press; 1974: 311-347.
19 Stabin MG, Sparks RB, Crowe E. OLINDA/ EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005; 46: 1023-1027.
20 Thomas SR, Stabin MG, Chen CT. et al. MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine. J Nucl Med 1999; 40: 102S-123S.
21 Tisljar U, Kloster G, Ritzl F. et al. Accumulation of radioiodinated L-alpha-methyltyrosine in pancreas of mice: concise communication. J Nucl Med 1979; 20: 973-976.
22 Vander Borght T, Asenbaum S, Bartenstein P. et al. EANM procedure guidelines for brain tumour imaging using labelled amino acid analogues. Eur J Nucl Med Mol Imaging 2006; 33: 1374-1380.