Direct validation of renal123I-MIBG scintigraphy in humans

Metaiodobenzylguanidine (MIBG) is a noradrenalin analogue that accumulates in
neurosecretory storage granules of adrenergic tissue and when labelled with
123Iodine, can be scintigraphically visualized. Since 123I-MIBG is not
metabolized, the 123I-MIBG scintigraphy storage reflects neuron integrity. This
technique is clinically and experimentally used to image the sympathetic
nervous system and has been validated on cardiac and adrenal tissue. Currently
in two studies (i.e. ENDORSE study ABR NL36755.018.11 and RENnervate study ABR
NL 42557.018.13, Dutch Trial Register numberNTR4005), 123I-MIBG scintigraphy is
being used to assess sympathetic function in renal tissue. Against the expected
results, the provisional results of these studies show an inter-individual
highly heterogeneous renal 123I-MIBG uptake, which could be either based on a
true difference or on a measurement error. It is unknown whether 123I-MIBG is
mainly taken up by the adrenergic renal tissue or that the by scintigraphy
visualized 123I-MIBG is mostly derived from urinary excretion. To the knowledge
of the researchers, the distribution of renal 123I-MIBG content has never been
studied directly and the renal 123I-MIBG scintigraphy has not been validated.
To rule out a measurement error, the current study will specifically validate
123I-MIBG on kidney tissue in humans.

to compare in vivo total kidney 123I-MIBG uptake (by counts per pixel) by
123I-MIBG scintigraphy to direct ex vivo 123I-MIBG uptake of the flushed kidney
as directly assessed with phosphor imaging.

One day prior to the surgery, patients will be administered 185 mBq of
123I-MIBG intravenously and will undergo a scintigraphy on 15 minutes and 4
hours postinjection at the department of nuclear medicine. Additionally a
low-dose SPECT-CT will be made 4 hours postinjection for anatomical
localization.
After the kidney is surgically removed, the kidney will be taken to the nuclear
medicine department and a scintigraphy will be made.
The study continues ex vivo.
The nephrectomised kidney will be taken to the nuclear medicine department and
a scintigram will be made.
Directly after performing the ex vivo 123I-MIBG scintigraphy, the kidney is
taken to the pathology department where the pathologist will perform the
routine inspection and preparation (e.g. assessment of the tumour) and prepares
3 specimens of from healthy kidney tissue. Thereafter the kidney will be
flushed with 0.9%NaCl and additionally 3 specimens will be taken.
Two of the flushed specimens and two of the unflushed specimens will be placed
on the phosphousplate for 24hr.
One flushed specimen and one unflushed specimen will be brought to the
neuropathology for immunohistochemical staining.

The amount of radiation the patients are exposed to is comparable to
approximately 2.5 times the yearly background radiation in the Netherlands.
This is an intermediate risk according to the ICRP62 (risks for 'average
adults'). (see *Stralingsadvies*). The intravenous canula will be placed for
the preparation of the operation anyway.