title: Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience.
abstract: Fifty patients with somatostatin receptor-positive tumors were treated with multiple doses of [(111)In-diethylenetriamine pentaacetic acid(0)]octreotide. Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160 GBq. Therapeutic effects were seen in 21 patients: partial remission in 1 patient, minor remissions in 6 patients, and stabilization of previously progressive tumors in 14 patients. Our results thus underscore the therapeutic potential of Auger-emitting radiolabelled peptides. The toxicity was generally mild bone marrow toxicity, but 3 of the 6 patients who received more than 100 GBq developed a myelodysplastic syndrome or leukemia. Therefore, we consider 100 GBq as the maximal tolerable dose. With a renal radiation dose of 0.45 mGy/MBq (based on previous studies) a cumulative dose of 100 GBq [(111)In-DTPA(0)]octreotide will lead to 45Gy on the kidneys, twice the accepted limit for external beam radiation. However, no development of hypertension, proteinuria, or significant changes in serum creatinine or creatinine clearance were observed in our patients including 2 patients who received 106 and 113 GBq [(111)In-DTPA(0)]octreotide without protection with amino acids, over a follow-up period of respectively 3 and 2 years. These findings show that the radiation of the short-range (maximal 10 microns) Auger electrons originating from the cells of the proximal tubules is not harmful for the renal function. The decrease in serum inhibin B and concomitant increase of serum FSH levels in men indicate that the spermatogenesis was impaired.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Roelf
authors.initials: R
authors.lastname: Valkema
authors.forename: Marion
authors.initials: M
authors.lastname: De Jong
authors.forename: Willem H
authors.initials: WH
authors.lastname: Bakker
authors.forename: Wout A p
authors.initials: WA
authors.lastname: Breeman
authors.forename: Peter P m
authors.initials: PP
authors.lastname: Kooij
authors.forename: Pieternella J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.forename: Frank H
authors.initials: FH
authors.lastname: De Jong
authors.forename: Arjan
authors.initials: A
authors.lastname: Christiansen
authors.forename: Boen L r
authors.initials: BL
authors.lastname: Kam
authors.forename: Wouter W
authors.initials: WW
authors.lastname: De Herder
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Geert
authors.initials: G
authors.lastname: Ensing
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000532:radiotherapy; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D017481:Receptors, Somatostatin / Q000032:analysis
chemical_list: D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide