The active uptake-1 mechanism at the cell membrane and neurosecretory storage granules in the cytoplasm of neuroblastoma are responsible for the uptake and retention of ¹³¹I-MIBG respectively. Although the radiopharmaceutical may be released from the granules, reuptake through this specific mechanism maintains prolonged intracellular concentration, in contrast to nonadrenergic tissues which rely on passive diffusion only, resulting in high tumor/non-tumor ratios. More than 90 % of pheochromocytomas and neuroblastomas concentrate MIBG, but lower sensitivities are found in medullary thyroid carcinoma (35 %) and carcinoid (70 %). Uptake of ¹³¹I-MIBG is tissue-specific for tumors derived from the neural crest.

Targeting peptide receptors on the cell surface, the somatostatine analogue ¹¹¹In-pentetreotide (octreotide) and 123I-labeled vasoactive intestinal peptide (VIP) are currently used for diagnostic scintigraphy of neuroendocrine tumors. By autoradiography somatostatin and VIP receptors have been demonstrated in varying prevalence in both neuroendocrine and other tumor types as well as in granulomatous disease and radiation pneumonitis, and VIP receptors were found to abund. Peptide receptor scintigraphy is very specific for these receptors rather than for the tumor type. After high doses (6.7 GBq) of ¹¹¹In-pentetreotide have been applied for therapy initially, phase I and phase II studies using ⁹⁰Y-labeled octreotide and lanreotide are now underway, with toxicity to the bone marrow and kidneys being the dose limiting factors.

Parallel to the introduction of radioiodinated MIBG in the early 80's, several monoclonal antibodies have been developed to antigens present on the cell surface of several neuroendocrine tumors, e.g. the use of murine UJ13A and anti-ganglioside G_D2 (¹³¹I-3F8) in neuroblastoma and anti-CEA antibodies in medullary thyroid carcinoma. Toxicity and HAMA response are the major limitations of this approach. More recent developments to overcome these problems include the use of chimeric antibodies, such as ¹³¹I-chCE7 in neuroblastoma, and multistep targeting techniques, such as the use of bispecific anti-CEA/anti-DTPA antibodies in medullary thyroid carcinoma.